bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular access for renal replacement therapy in acute kidney injury: Are nontunneled catheters the right choice?
Authors: Kelly Yvelynne P. , Mendu Mallika L.
Published: August 2019

Renal replacement therapy (RRT) in the setting of acute kidney injury (AKI) is generally provided by either tunneled or nontunneled dialysis catheters (TDCs or NTDCs), used immediately after insertion. Current consensus guidelines suggest using NTDCs rather than TDCs for vascular access in AKI primarily for logistical reasons, including ease of insertion and timeliness. However, there is increasing evidence that, compared to NTDCs, TDCs are associated with fewer complications (mechanical and infectious) and better dialysis delivery. Nevertheless, this evidence must be balanced by the feasibility and practicality of implementing a “TDC‐first approach.” In this paper, we assess the current evidence base for vascular access choice for AKI requiring RRT. We make the case for increased use of TDCs as first‐line vascular access given growing observational evidence for improved patient outcomes; including decreased risk of infection and thrombosis, increased blood flow rates and decreased treatment interruptions, compared to NDTCs. We advocate for further research to test the feasibility and outcomes associated with a TDC‐first approach to AKI‐RRT access. A TDC‐first approach has the potential to improve RRT clinical outcomes and reduce resource utilization and cost.
Older sibling contribution to younger children's working memory and cognitive flexibility
Authors: Hill Tatiana Yasmeen , Palacios Natalia
Published: August 2019

We used structural equation modeling in the Early Childhood Longitudinal Study—Kindergarten Cohort (N = 17,020) to explore the influence of having an older sibling on kindergarten‐age focal children's cognitive self‐regulation. In model 1, we tested how having a sibling who is generally older than the focal child contributes to the focal child's working memory (WM) and cognitive flexibility (CF) upon entering kindergarten. In model 2, we assessed the contribution to the focal child's kindergarten WM and CF of having an older sibling in a non‐proximal age range (age 12–18) or not having siblings relative to having an older sibling in a proximal age range to the focal child (up to age 11). In model 3, we considered the contribution of having an older sister, an older brother, or both an older sister and an older brother of any age. Having an older sibling in general was associated with increased kindergarten WM, whereas having an older sister was related to increased WM and CF. Compared to having a proximal older sibling, having no siblings and having a non‐proximal older sibling were related to decreased WM and CF. Findings have implications for involving siblings in family interventions in early childhood.
Identification of a new allele, HLA‐DRB1*01:01:01:02 discovered using third‐generation sequencing
Authors: Liu Yi‐Ling , Macpherson Hannah L. , Pryke Oliver L. , Marsh Steven G. E. , Mayor Neema P.
Published: August 2019

HLA‐DRB1*01:01:01:02 is the first reported intronic variant of DRB1*01:01:01, differing by a single nucleotide substitution.
Disseminated toxoplasmosis associated with hemophagocytic syndrome after kidney transplantation: A case report and review
Authors: Gay Juliette , Gendron Nicolas , Verney Charles , Joste Valentin , Dardé Marie‐Laure , Loheac Charlotte , Vrtovsnik François , Argy Nicolas , Houze Sandrine
Published: August 2019

Disseminated toxoplasmosis is infrequent after kidney transplant transmission but life‐threatening because of a lack of diagnostic suspicion as well as specific chemoprophylaxis recommendations. Solid organ transplantation has resulted in few cases of disseminated toxoplasmosis presenting with associated hemophagocytic syndrome. Herein, we report, within the context of a donor/receiver mismatch, a case of a toxoplasmosis associated with hemophagocytic syndrome in a kidney transplant recipient. Molecular and serological investigations confirmed Toxoplasma gondii transmission through the kidney graft.
A novel protocol for cryopreservation of paediatric red blood cell units allows increased availability of rare blood types
Authors: Larsson Linda , Larsson Stella , Derving Julia , Watz Emma , Uhlin Michael
Published: August 2019

Background and objectives

There is a growing concern for shortage in future blood supply, caused by a predicted decrease in eligible blood donors and simultaneous increase in recipients. Cryopreservation of split red blood cell units could increase stock supply by reducing waste of rare blood. This would be particularly useful in paediatric care where very small volumes often are transfused. The aim of this study was to develop a cryopreservation protocol for split units using the closed‐system automated cell processor ACP215, as such protocols are currently missing.

Materials and methods

Using a pool‐and‐split design, red blood cell units (N = 8) were glycerolized and frozen, either as standard volume reference units, or further divided into three smaller split units each. After thawing/deglycerolization, the supernatant of the smaller splits was reduced by additional centrifugation, and new SAGM was added to 60% haematocrit. The units were analysed for storage lesion effects up to ten days post‐thawing.

Results

Haemolysis and extracellular potassium ion levels were lower in the split units than in the whole units from day three onwards. The metabolic parameters pH, ATP, glucose and lactate were also lower, though likely caused by lower additive solution pH rather than storage.

Conclusion

Split units of red blood cells can be successfully cryopreserved using the ACP215. In addition to favourably low haemolysis and potassium, they also have higher haematocrit than corresponding whole units and enable involvement of fewer donors at repeated transfusions. These characteristics are all desirable features in paediatric care.
The use of prehospital blood products in the resuscitation of trauma patients: a review of prehospital transfusion practices and a description of our regional whole blood program in San Antonio, TX
Authors: Pokorny Douglas M. , Braverman Maxwell A. , Edmundson Philip M. , Bittenbinder David M. , Zhu Caroline S. , Winckler Christopher J. , Schaefer Randall , McGinity Ashley C. , Epley Eric , Eastridge Brian J. , Nicholson Susannah E. , Stewart Ronald M. , Jenkins Donald H.
Published: August 2019

Background

Prehospital management of the traumatically injured patient has evolved significantly since the organization of emergency medical services across the United States in the 1970s. Initially focusing on the utilization of crystalloid solutions to restore shed blood volume, robust military and civilian trauma experiences led to a modern day shift towards balanced blood component and ultimately whole blood use for immediate volume replacement. In addition, prehospital transfusion or remote damage control resuscitation (RDRC) has been widely adopted. This has led to point of injury resuscitation using blood products both in the United States and abroad.

Objectives

This article will review the evolution of civilian and military prehospital resuscitation as well as the current practice of prehospital whole blood transfusion in the civilian trauma population in the United States. Additionally, we will provide an overview of our regional trauma system's use of whole blood with focus on the programme infrastructure, donor programme, product rotation schedule and logistical challenges. Finally, we provide three case report examples of the effective use of whole blood in our civilian emergency medical services (EMS) programs.
Birational geometry of the moduli space of quartic surfaces
Authors: Laza Radu , O’Grady Kieran
Published: August 2019

By work of Looijenga and others, one understands the relationship between Geometric Invariant Theory (GIT) and Baily–Borel compactifications for the moduli spaces of degree-$2$ $K3$surfaces, cubic fourfolds, and a few other related examples. The similar-looking cases of degree-$4$ $K3$surfaces and double Eisenbud–Popescu–Walter (EPW) sextics turn out to be much more complicated for arithmetic reasons. In this paper, we refine work of Looijenga in order to handle these cases. Specifically, in analogy with the so-called Hassett–Keel program for the moduli space of curves, we study the variation of log canonical models for locally symmetric varieties of Type IV associated to$D$-lattices. In particular, for the$19$-dimensional case, we conjecturally obtain a continuous one-parameter interpolation between the GIT and Baily–Borel compactifications for the moduli of degree-$4$ $K3$surfaces. The analogous$18$-dimensional case, which corresponds to hyperelliptic degree-$4$ $K3$surfaces, can be verified by means of Variation of Geometric Invariant Theory (VGIT) quotients.
Mechanisms underlying the influence of oestrogen on cardiovascular physiology in women
Authors: Novella Susana , Pérez‐Cremades Daniel , Mompeón Ana , Hermenegildo Carlos
Published: August 2019

Women show a lower incidence of cardiovascular diseases than age‐matched men, but this benefit disappears after menopause. Oestrogen‐mediated vascular actions are mainly attributed to oestradiol and exerted by oestrogen receptors (ERα, ERβ and G protein‐coupled oestrogen receptor), through rapid and/or genomic mechanisms, but these effects depend on ageing and inflammation. A cardiovascular approach in women's health has arisen due to controversy regarding oestrogen's beneficial impact as reported in experimental and observational studies and large randomized trials. These can be explained, in part, by two mutually non‐exclusive hypotheses. On the one hand, the timing hypothesis, which states that oestrogen‐mediated benefits occur before the detrimental effects of ageing are established in the vasculature; on the other hand, ageing and/or hormonal‐associated changes in ER expression that could lead to a deleterious imbalance in favour of ERβ over ERα, generally associated with higher inflammation and endothelial dysfunction. In experimental studies, oestradiol acting on ERα promotes the release of vasoactive compounds such as nitric oxide (NO) and prostacyclin, and shifts the angiotensin axis towards angiotensin 1–7 production. Mechanisms underlying oestradiol vascular function also include anti‐inflammatory and epigenetic modifications. 17β‐Oestradiol changes the transcriptomic profile of endothelial cells, and the involvement of miRNA in the regulatory pathways of vascular function reinforces assumptions regarding the vascular actions of oestrogen. Thus, the present Symposium Review aims to postulate the role of ERα in oestrogen modulation of endothelium‐derived mediators and vascular physiology, as well as its relationship with miRNA and inflammation, and elucidate how physiological changes in postmenopausal women counteract the observed effects.

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Campesinos, corredores y el Estado: Competencia y dividendos en la política local familiarista en dos pueblos del noroccidente de Portugal
Authors: Silva Manuel Carlos
Published: August 2019

Para explicar el “conservatismo” de los campesinos en el noroccidente de Portugal, al igual que los obstáculos al desarrollo local rural, el autor enfatiza en este artículo –además de subrayar en otra parte la especificidad de la economía campesina y varias estrategias de los moradores rurales (matrimonio, herencia y migración)– la relevancia del factor político, es decir, la dependencia de la mayoría de los residentes que enfrentan a los viejos y nuevos patrones locales (caciques). Estos últimos en una estrategia de reproducir el poder local sobre una base familiarista someten a los primeros bien sea mediante imperativos morales o bien mediante dádivas, favores administrativos y financieros, convirtiendo esos favores en beneficios familiares o dividendos políticos y económicos.
Size-Independent Mechanical Response of Ultrathin Carbon Nanotube Films in Mesoscopic Distinct Element Method Simulations
Authors: Ostanin Igor , Dumitrică Traian , Eibl Sebastian , Rüde Ulrich
Published: August 2019

In this work, we present a computational study of the small strain mechanics of freestanding ultrathin carbon nanotube (CNT) films under in-plane loading. The numerical modeling of the mechanics of representatively large specimens with realistic micro- and nanostructure is presented. Our simulations utilize the scalable implementation of the mesoscopic distinct element method of the waLBerla multi-physics framework. Within our modeling approach, CNTs are represented as chains of interacting rigid segments. Neighboring segments in the chain are connected with elastic bonds, resolving tension, bending, shear, and torsional deformations. These bonds represent a covalent bonding within the CNT surface and utilize enhanced vector model (EVM) formalism. Segments of the neighboring CNTs interact with realistic coarse-grained anisotropic van der Waals potential, enabling a relative slip of CNTs in contact. The advanced simulation technique allowed us to gain useful insights on the behavior of CNT materials. It was established that the energy dissipation during CNT sliding leads to extended load transfer that conditions size-independent, material-like mechanical response of the weakly bonded assemblies of CNTs.
A Bird-Inspired Perching Landing Gear System1
Authors: Nadan Paul M. , Anthony Tatiana M. , Michael Duncan M. , Pflueger Jeffrey B. , Sethi Manik S. , Shimazu Kelli N. , Tieu Mindy , Lee Christopher L.
Published: August 2019

The design, modeling, simulation, and testing of a landing gear system that enables a UAV to perch on an object or surface is presented here. The working principle of the landing gear is inspired by the anatomy of birds that grasp and perch as tendons in their legs and feet are tensioned. In a similar fashion, as the UAV sets down on a structure, its weight tensions a cable which actuates opposing, flexible, multi-segment feet to enclose the target. To analyze the grasping capability of the design, a hybrid empirical–computational model is developed that can be used to simulate the kinematics of the system as it grasps objects of various cross-sectional shapes and sizes. The model relates the curvature of the feet to the displacement and tension of the cable tendon. These quantities are then related to the weight of the UAV through the leg geometry. It also evaluates enclosure and calculates contact forces to quantitatively characterize the grasp. Results demonstrate how the model can be used by designers to determine how a UAV can perch upon a structure of a given shape and size. If perched, the minimum weight required to maintain its position is calculated. A prototype system was fabricated, analyzed, and tested on a radio-controlled hexacopter. Experiments show that the landing gear enables the hexacopter to land, perch, and takeoff from a variety of objects. Finally, we begin to investigate the scalability of the concept with a smaller, lighter design.
Deep Learning of Variant Geometry in Layerwise Imaging Profiles for Additive Manufacturing Quality Control
Authors: Imani Farhad , Chen Ruimin , Diewald Evan , Reutzel Edward , Yang Hui
Published: August 2019

Additive manufacturing (AM) is a new paradigm in design-driven build of customized products. Nonetheless, mass customization and low-volume production make the AM quality assurance extremely challenging. Advanced imaging provides an unprecedented opportunity to increase information visibility, cope with the product complexity, and enable on-the-fly quality control in AM. However, in situ images of a customized AM build show a high level of layer-to-layer geometry variation, which hampers the use of powerful image-based learning methods such as deep neural networks (DNNs) for flaw detection. Very little has been done on deep learning of variant geometry for image-guided process monitoring and control. The proposed research is aimed at filling this gap by developing a novel machine learning approach that is focused on variant geometry in each layer of the AM build, namely region of interests, for the characterization and detection of layerwise flaws. Specifically, we leverage the computer-aided design (CAD) file to perform shape-to-image registration and to delineate the regions of interest in layerwise images. Next, a hierarchical dyadic partitioning methodology is developed to split layer-to-layer regions of interest into subregions with the same number of pixels to provide freeform geometry analysis. Then, we propose a semiparametric model to characterize the complex spatial patterns in each customized subregion and boost the computational speed. Finally, a DNN model is designed to learn variant geometry in layerwise imaging profiles and detect fine-grained information of flaws. Experimental results show that the proposed deep learning methodology is highly effective to detect flaws in each layer with an accuracy of 92.50 ± 1.03%. This provides a significant opportunity to reduce interlayer variation in AM prior to completion of a build. The proposed methodology can also be generally applicable in a variety of engineering and medical domains that entail customized design, variant geometry, and image-guided process control.
Water Hammer Causes Water Main Breaks
Authors: Leishear Robert A.
Published: August 2019

Most underground water main breaks can be stopped, since the technology is now available to evaluate water system piping failures and determine corrective actions. The problem is defined in terms of several variables: (1) Water hammer is the initiator of nearly all underground water main breaks. (2) In nonacidic soils, fatigue directly causes piping cracks. (3) In acidic soils, water hammer cracks the pipes, and crevice corrosion is accelerated at those crack sites. Additionally, those cracks serve as moisture sources to induce piping surface corrosion due to galvanic corrosion between the soil and the metallic pipe wall. Even so, some failures are solely due to corrosion. (4) Dynamic pipe stresses are significantly larger than stresses caused by static loading, i.e., hoop stresses and strains may be as much as four times the calculated static stress due to water hammer. (5) If dynamic stresses are not considered, calculations incorrectly conclude that water mains will not be damaged. (6) That is, water hammer calculations determine pressure surge magnitudes that are multiples of the operating pressures, where dynamic effects cause fatigue cracks due to the applied pressures and the number of cycles for those pressures to break water mains.
Experimental Investigation of Thermohydraulic Performance of the Solar Air Heater Having Arc-Shaped Ribs With Multiple Gaps
Authors: Jain Sheetal Kumar , Agrawal Ghanshyam Das , Misra Rohit
Published: August 2019

In the present research, the thermohydraulic performance of a solar air heater having artificial roughness in the form of arc-shaped ribs with multiple gaps has been investigated experimentally and compared with that of a solar air heater having smooth absorber plate. The performance has been investigated in terms of enhancement in the Nusselt number and friction factor. Results of the present work have also been compared with previously published work. Reynolds number and arc angle (α) were varied from 3000 to 18,000 and 30 deg to 75 deg, respectively. Present roughness results in a higher rate of heat transfer from the absorber surface to air, but it also imposes a penalty in terms of the increased friction factor. Maximum enhancement in Nusselt number, friction factor, and thermohydraulic performance parameter for the roughened absorber surface is found to be 3.74, 2.69, and 2.75 times that of the smooth plate, respectively. Correlations of heat transfer and friction factor for proposed roughness have also been developed.
Combined Effects of Fluid Yield Stress and Geometrical Arrangement on Natural Convection in a Square Duct From Two Differentially Heated Horizontal Cylinders
Authors: Mishra Lubhani , Chhabra R. P.
Published: August 2019

Laminar natural convection in Bingham plastic fluids has been investigated from two differentially heated cylinders arranged either one above the other or along the diagonal of the square enclosure. The coupled momentum and energy equations have been solved to elucidate the effect of Rayleigh number (104–106), Prandtl number (10–100), Bingham number (0.01 to Bnmax), and the gap between the two cylinders in terms of the geometric parameters (0 to −0.25 for vertical alignment and 0.15 to 0.35 for diagonal alignment) on the detailed structure of the flow field and the overall heat transfer characteristics of the system. New extensive results are visualized in terms of streamlines, isotherm contours, and variation of the local Nusselt number along various surfaces. Additional insights are developed by examining the shear-rate contours and the yield surfaces delineating the fluid-like and solid-like regions in the flow domain. At high values of the Bingham number, the average Nusselt number reaches its asymptotic value corresponding to the conduction limit. The increasing Rayleigh number promotes fluid-like behavior which promotes heat transfer. The augmentation in heat transfer depends on the volume of fluid participating in the buoyancy-induced flow. For the vertical arrangement, the average Nusselt number (for the heated cylinder) decreases a little as these are moved slightly away from the center of the enclosure, followed by an increase as the two cylinders approach one of the sidewalls; this is so even in the conduction limit. In contrast, when the two cylinders are arranged along the diagonal, the Nusselt number progressively decreases as the gap between the two cylinders increases. Finally, predictive correlations have been developed for the average Nusselt number and the limiting Bingham number thereby enabling their estimation in a new application.
Thin Gas Film Isothermal Condensation in Aerodynamic Bearings
Authors: Guenat Eliott , Schiffmann Jürg
Published: August 2019

High-speed small-scale turbomachinery for waste heat recovery and vapor compression cycles is typically supported on gas-lubricated bearings operating close to the saturation conditions of the lubricant. Under particular conditions, the gas film might locally reach the saturation pressure with potentially hazardous effects on the performance of the gas bearing. The present work introduces a model based on the Reynolds equation and the development of cavitation modeling in liquid-lubricated bearings for condensing gas bearings. The effect of condensation on load capacity and pressure and density profiles is investigated for two one-dimensional bearing geometries (parabolic and Rayleigh step) and varying operating conditions. The results suggest that the load capacity is generally negatively affected if condensation occurs. An experimental setup consisting of a Rayleigh-step gas journal bearing with pressure taps to measure the local fluid film pressure is presented and operated in R245fa in near-saturated conditions. The comparison between the evolution of the fluid film pressure under perfect gas and near saturation conditions clearly suggests the occurrence of condensation in the fluid film. These results are corroborated by the very good agreement with the model prediction.
REVIEWS OF ACOUSTICAL PATENTS
Authors: Fulop Sean A.
Published: August 2019

The purpose of these acoustical patent reviews is to provide enough information for a Journal reader to decide whether to seek more information from the patent itself. Any opinions expressed here are those of the reviewers as individuals and are not legal opinions. Patents are available via the internet at the USPTO website, and also using Google Patents.
Entanglement classifier in chemical reactions
Authors: Li Junxu , Kais Sabre
Published: August 2019

This study generalizes the standard Bell’s inequality from discrete to continuous measurement results.
TB or not TB: Type 3 ILCs may decide
Authors: McManus Duneia , Iyer Akshay , Pillai Asha B.
Published: August 2019

Mouse models are used to show that type 3 innate lymphoid cells provide early protection against
Mtb
infection.
Effect of monitor positioning on visual attention and situation awareness during neonatal resuscitation: a randomised simulation study
Authors: Law Brenda Hiu Yan , Cheung Po-Yin , van Os Sylvia , Fray Caroline , Schmölzer Georg M
Published: August 2019

Objectives

To compare situation awareness (SA), visual attention (VA) and protocol adherence in simulated neonatal resuscitations using two different monitor positions.

Design

Randomised controlled simulation study.

Settings

Simulation lab at the Royal Alexandra Hospital, Edmonton, Canada.

Participants

Healthcare providers (HCPs) with Neonatal Resuscitation Program (NRP) certification within the last 2 years and trained in neonatal endotracheal intubations.

Intervention

HCPs were randomised to either central (eye-level on the radiant warmer) or peripheral (above eye-level, wall-mounted) monitor positions. Each led a complex resuscitation with a high-fidelity mannequin and a standardised assistant. To measure SA, situation awareness global assessment tool (SAGAT) was used, where simulations were paused at three predetermined points, with five questions asked each pause. Videos were analysed for SAGAT and adherence to a NRP checklist. Eye-tracking glasses recorded participants’ VA.

Main outcome measure

The main outcome was SA as measured by composite SAGAT score. Secondary outcomes included VA and adherence to NRP checklist.

Results

Thirty simulations were performed; 29 were completed per protocol and analysed. Twenty-two eye-tracking recordings were of sufficient quality and analysed. Median composite SAGAT was 11.5/15 central versus 11/15 peripheral, p=0.56. Checklist scores 46/50 central versus 46/50 peripheral, p=0.75. Most VA was directed at the mannequin (30.6% central vs 34.1% peripheral, p=0.76), and the monitor (28.7% central vs 20.5% peripheral, p=0.06).

Conclusions

Simulation, SAGAT and eye-tracking can be used to evaluate human factors of neonatal resuscitation. During simulated neonatal resuscitation, monitor position did not affect SA, VA or protocol adherence.
Metallic embolus to the brain in a patient with mechanical heart valves: an extremely rare complication
Authors: Sagheer Shazib , Sheikh Abu Baker , Hallstrom Jon J , Raizada Veena
Published: August 2019

A 46-year-old man with a medical history of rheumatic valve disease underwent mitral and aortic valve replacements with On-X and CarboMedics Top Hat supra-annular mechanical valves, respectively. Seven months after the valve replacement surgery, the patient presented with dizziness. A CT scan of the brain was done as part of a thorough workup of dizziness. The CT scan revealed a small metallic density in the M2 branch of the right middle cerebral artery. The metallic density was believed to be a metallic embolus that originated from the mechanical valves or the suturing material, that is, Cor-Knot fastener. Although in our case, the dizziness was believed to be the result of benign paroxysmal positional vertigo, through this case, we aim to highlight this extremely rare structural complication of mechanical valves. This complication can have serious and potentially fatal consequences such as embolic component-related stroke or another organ infarction.
Close encounters of the US kind: illness and injury among US athletes at the PyeongChang 2018 Winter Olympic Games
Authors: Nabhan Dustin , Windt Johann , Taylor David , Moreau William
Published: August 2019

Aim

To describe injury and illness incidence during the 2018 Winter Olympic Games (WOG) by Team USA.

Methods

A descriptive observational study. We used registered Team USA Olympic athletes’ electronic medical records to review preparticipation health histories and medical encounters immediately prior to and throughout the 2018 WOG. Medical encounters were defined as all medical services provided by a healthcare provider, including evaluation, treatment and prophylactic services. All medical conditions were described according to International Olympic Committee injury and illness reporting criteria.

Results

Team USA included 134 men and 108 women, aged 18–39 years, who represented 17 sport federations. The 47 Team USA medical staff documented 1744 medical encounters on 242 registered athletes (7.2 medical encounters per athlete). Forty-seven illnesses (194.2/1000 athletes) and 32 time loss injuries (132.2/1000 athletes) were recorded during the Games.

Conclusions

An injury surveillance programme consisting of an electronic preparticipation health history and surveillance of medical encounters during the WOG was used to describe the health status of Team USA. We noted limitations to the surveillance process that can be addressed at future events.
Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)
Authors: Veltkamp Floor , Khan Djera H , Reefman Christa , Veissi Susan , van Oers Hedy A , Levtchenko Elena , Mathôt Ron A A , Florquin Sandrine , van Wijk Joanna A E , Schreuder Michiel F , Haverman Lotte , Bouts Antonia H M
Published: August 2019

Introduction

Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome).

Methods and analysis

An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2–16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores.

Ethics and dissemination

The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.

Trial registration number

NL6826, 2017-001025-41
Numerical study of flow pattern around lateral intake in a curved channel
Authors: Montaseri Hossien , Asiaei Hossein , Baghlani Abdolhossein , Omidvar Pourya
Published: August 2019

This paper deals with numerical study of flow field in a channel bend in presence of a lateral intake using three-dimensional numerical model SSIIM2. The effects of bend on the structure of the flow around the intake are investigated and compared with the experimental data. The tests are carried out in a U-shaped channel bend with a lateral intake. The intake is located at the outer bank of an 180∘ bend at position 115∘ with 45∘ diversion angle and the experimental data can be used to calibrate and validate numerical models. The results show that both the center-region and outer-bank cross-stream circulations are observed in the experiments while only the former is captured by the numerical model due to the limitations of the turbulence model. In the curved channel after the intake, both experimental and numerical results show another type of bi-cellular circulations in which clockwise center-region circulations and counterclockwise circulations near the inner bank and the free surface (inner-bank circulations) are captured. The study shows that the numerical model very satisfactorily predicts streamlines, velocity field and flow pattern in the channel and in vicinity of the intake. Investigation of flow pattern around lateral intake in channel bends shows that contrary to the case of flow diversion in straight channels, the width of the dividing stream surface near water surface level is greater than that of near bed level. Finally, the effects of position and diversion angle of the lateral intake, discharge ratio and upstream Froude number on the flow pattern are investigated.
Experimental and Theoretical Investigation on Bistable Symmetric Shells Built by Locally Nanostructuring Isotropic Rectangular Plates
Authors: Yi Shenghui , He Xiaoqiao , Lu Jian
Published: August 2019

A new bistable shell with two symmetric configurations is proposed by using the nanotechnology, surface mechanical attrition treatment (SMAT), to locally treat a rectangular region. The impacts from randomly fast moving balls during the process induce nanotwins and mesh material grains into nanoscale on originally flat plates, which largely increase the material’s yield strength and elastic deformation capacity. Also, the plastic deformations accumulated from thousands of impacts may stretch the plate under the constraint from the untreated region, while inducing internal compressive forces in the processed region. The experiments show that, when the accumulated plastic deformations are large enough, the locally nanostructured plate may buckle transversely by the internal forces to hold two different stable configurations, resulting in the bistable feature. An analytical model is developed to predict the stable configurations, which is numerically verified and experimentally validated. The parameters, including the SMAT region, plate dimensions, and SMAT process, to design the stable configurations of the bistable shells are systematically studied experimentally, analytically, and numerically.
Evaluations of Coupled Transverse-Rotational Galloping of Slender Structures with Nonlinear Effect
Authors: Chen Jie , Li Qiu-Sheng
Published: August 2019

This paper presents evaluations of coupled two-degree-of-freedom (2DOF) galloping oscillations of slender structures with nonlinear effects, involving coupled transverse and rotational motions. The nonlinear governing equations of the coupled motions are derived by developing nonlinear formulations of the quasi-steady aerodynamic forces and damping coefficients. By solving the eigenvalue problem of a perfectly tuned 2DOF system, an analytical expression of the minimal structural damping ratio required to prevent coupled transverse-rotational galloping is established. The influences of various parameters, such as angle of wind attack, structural height, width and aspect ratio, on the onset wind velocity for the occurrence of coupled galloping are then analyzed in detail by numerical simulations. Comparisons of the onset wind velocity of the coupled 2DOF and uncoupled single-degree-of-freedom (1DOF) galloping are presented and discussed. The nonlinear vibration behavior of coupled 2DOF galloping of slender structures under varying wind speeds is also investigated.
Measuring consistency among gene set analysis methods: A systematic study
Authors: Maleki Farhad , Ovens Katie L. , Hogan Daniel J. , Rezaei Elham , Rosenberg Alan M. , Kusalik Anthony J.
Published: August 2019

Gene set analysis is a quantitative approach for generating biological insight from gene expression datasets. The abundance of gene set analysis methods speaks to their popularity, but raises the question of the extent to which results are affected by the choice of method. Our systematic analysis of 13 popular methods using 6 different datasets, from both DNA microarray and RNA-Seq origin, shows that this choice matters a great deal. We observed that the overall number of gene sets reported by each method differed by up to 2 orders of magnitude, and there was a bias toward reporting large gene sets with some methods. Furthermore, there was substantial disagreement between the 20 most statistically significant gene sets reported by the methods. This was also observed when expanding to the 100 most statistically significant reported gene sets. For different datasets of the same phenotype/condition, the top 20 and top 100 most significant results also showed little to no agreement even when using the same method. GAGE, PAGE, and ORA were the only methods able to achieve relatively high reproducibility when comparing the 20 and 100 most statistically significant gene sets. Biological validation on a juvenile idiopathic arthritis (JIA) dataset showed wide variation in terms of the relevance of the top 20 and top 100 most significant gene sets to known biology of the disease, where GAGE predicted the most relevant gene sets, followed by GSEA, ORA, and PAGE.
From Offense Dominance to Deterrence: China’s Evolving Strategic Thinking on Cyberwar
Authors: Jiang Tianjiao
Published: August 2019

This paper examines China’s strategic thinking on cyberwar. It has been widely argued that the People’s Liberation Army (PLA) has shown strong interest in launching large-scale cyberattacks against the US during warfare or peacetime. However, such views ignore the fact that the PLA must restrain itself due to the uncertainties of cyberattack, such as collateral damage, blowback, and escalation. In fact, Chinese experts follow US perceptions and cyberwar practices very closely, which has contributed to Beijing’s evolving strategic thinking over the past decades. From the 1990s to early 2000s, the “ideology of offense” was the PLA’s primary approach to the “informationization leaping forward”. Due to the shock of the Gulf War, most of the military strategists advocated cyber offense in order to catch up with the new round of revolution in military affairs. However, after 2008, both military and civilian experts started to increasingly question the effectiveness of cyberattack after studying their peers’ criticism against cyber deterrence in the US. There was no consensus on national cybersecurity strategy until 2015 when there was a call for China to develop a cyber deterrence strategy as a reaction to the further development of cyber deterrence by the US. The latest Chinese official documents on cybersecurity have reflected the shift of its strategic thinking.
A phase equilibrium investigation of selected source controls on the composition of melt batches generated by sequential melting of an average metapelite
Authors: Mayne Matthew J. , Stevens Gary , Moyen Jean-François
Published: August 2019

The ability of Rcrust software to conduct path-dependent phase equilibrium modelling with automated changing bulk compositions allows for a phase equilibrium approach to investigate an array of source controls for their effect on the bulk compositions of melts produced by sequential melting events. The following source controls of the rock system are considered: (1) initial magnesium and iron content; (2) initial sodium and calcium content; (3) pressure–temperature path followed by the system; and (4) threshold by which melt extractions in the system are triggered. These source controls are investigated in a water-restricted system and a water-in-excess system. The permutation of these cases resulted in 128 different modelled pressure–temperature bulk composition paths investigating the melting of an average pelite composition. The resultant melt compositions are compared to that of a natural granite dataset and provide a good fit for the incompatible elements Na
2
O and K
2
O with the allowance that granites most likely form as magmas consisting of melt and ferromagnesian-rich crystals. The fluid state of the system is shown to have the strongest control on melt compositions, with the pressure–temperature path having subordinate control on the volume and composition of melts produced.
Using Informed Design in Informal Computer Science Programs to Increase Youths’ Interest, Self-efficacy, and Perceptions of Parental Support
Authors: Clarke-Midura Jody , Sun Chongning , Pantic Katarina , Poole Frederick , Allan Vicki
Published: August 2019

Our work is situated in research on Computer Science (CS) learning in informal learning environments and literature on the factors that influence girls to enter CS. In this article, we outline design choices around the creation of a summer programming camp for middle school youth. In addition, we describe a near-peer mentoring model we used that was influenced by Bandura's self-efficacy theory. The purpose of this article, apart from promoting transparency of program design, was to evaluate the effectiveness of our camp design in terms of increasing youths’ interest, self-efficacy beliefs, and perceptions of parental support. We found significant gains for all three of these concepts. Additionally, we make connections between our design choices (e.g., videos, peer support, mentor support) and the affective gains by thematically analyzing interview data concerning the outcomes found in our camps.
Cardiac troponin-I phosphorylation underlies myocardial contractile dysfunction induced by hypothermia rewarming
Authors: Tveita Torkjel , Arteaga Grace M. , Han Young-Soo , Sieck Gary C.
Published: August 2019

Rewarming the intact heart after a period of hypothermia is associated with reduced myocardial contractility, decreased Ca2+ sensitivity, and increased cardiac troponin-I (cTnI) phosphorylation. We hypothesized that hypothermia/rewarming (H/R) induces left ventricular (LV) contractile dysfunction due to phosphorylation of cTnI at Ser23/24. To test this hypothesis, the response of wild-type mice ( n = 7) to H/R was compared with transgenic (TG) mice expressing slow skeletal TnI (TG-ssTnI; n = 7) that lacks the Ser23/24 phosphorylation sites. Hypothermia was induced by surface cooling and maintained at 23–25°C for 3 h. Subsequently, the animals were rewarmed to 37°C. LV systolic and diastolic function was assessed using a 1.4 F pressure-volume Millar catheter introduced via the right carotid artery. At baseline conditions, there were no significant differences in LV systolic function between wild-type and TG-ssTnI mice, whereas measurements of diastolic function [isovolumic relaxation constant (τ) and end-diastolic pressure-volume relationship (EDPVR)] were significantly ( P < 0.05) reduced in TG-ssTnI animals. Immediately after rewarming, significant differences between groups were found in cardiac output (CO; wild-type 6.6 ± 0.7 vs. TG-ssTnI 8.8 ± 0.7 mL/min), stroke work (SW; wild-type 796 ± 112 vs. TG-ssTnI 1208 ± 67 mmHg/μL), and the preload recruited stroke work (PRSW; wild-type 38.3 ± 4.9 vs. TG-ssTnI 68.8 ± 8.2 mmHg). However, EDPVR and τ returned to control levels within 1 h in both groups. We conclude that H/R-induced LV systolic dysfunction results from phosphorylation of cTnI at Ser23/24.

NEW & NOTEWORTHY Rewarming following a period of accidental hypothermia leads to a form of acute cardiac failure (rewarming shock), which is in part due to reduced sensitivity to Ca2+ activation of myocardial contraction. The results of the present study support the hypothesis that rewarming shock is due to phosphorylation of cardiac troponin I.
FABP4gene has a very large effect on feed efficiency in lactating Israeli Holstein cows
Authors: Cohen-Zinder Miri , Lipkin Ehud , Shor-Shimoni Einav , Ben-Meir Yehoshav , Agmon Rotem , Asher Aviv , Miron Joshua , Shabtay Ariel
Published: August 2019

Improving feed efficiency (FE) is a major goal for the livestock industry. Previously, we have identified 48 SNP markers distributed over 32 genes significantly associated with residual feed intake (RFI) in Israeli Holstein male calves, the most significant of which are located in the bovine FABP4 gene. In the present study, we tested associations of eight of the FABP4 markers with RFI and feed conversion ratio (FCR), along with milk composition and feeding behavioral traits, in 114 lactating Israeli Holstein cows. Large allele effects were found, along with large contributions of FABP4 markers to the phenotypic variation [mean contribution of all significant markers ( P < 0.05), 15.4 and 12.0% for RFI and FCR, respectively] and genotypic variation [means of all significant markers ( P < 0.05), 75.7 and 32.4% in RFI and FCR, respectively]. However, the association of all significant FABP4 markers with FE and milk content traits was found in opposite directions, such that improved FE was accompanied by decreased milk content. Hence, before inclusion in breeding programs, the gain in FE must be economically balanced with the loss in milk contents. On the other hand, these findings imply that in any current improvement program concentrated on milk traits alone, without taking into account the effect on FE, the progress in milk composition is probably accompanied by deterioration of FE. These results, if confirmed in other populations and breeds, set FABP4 as a prime candidate in any marker-assisted selection program targeting FE as a whole and RFI in particular.
Patient-Derived Xenografts and Matched Cell Lines Identify Pharmacogenomic Vulnerabilities in Colorectal Cancer
Authors: Lazzari Luca , Corti Giorgio , Picco Gabriele , Isella Claudio , Montone Monica , Arcella Pamela , Durinikova Erika , Zanella Eugenia R. , Novara Luca , Barbosa Fabiane , Cassingena Andrea , Cancelliere Carlotta , Medico Enzo , Sartore-Bianchi Andrea , Siena Salvatore , Garnett Mathew J. , Bertotti Andrea , Trusolino Livio , Di Nicolantonio Federica , Linnebacher Michael , Bardelli Alberto , Arena Sabrina
Published: August 2019

Purpose:

Patient-derived xenograft (PDX) models accurately recapitulate the tumor of origin in terms of histopathology, genomic landscape, and therapeutic response, but some limitations due to costs associated with their maintenance and restricted amenability for large-scale screenings still exist. To overcome these issues, we established a platform of 2D cell lines (xeno-cell lines, XL), derived from PDXs of colorectal cancer with matched patient germline gDNA available.

Experimental Design:

Whole-exome and transcriptome sequencing analyses were performed. Biomarkers of response and resistance to anti-HER therapy were annotated. Dependency on the WRN helicase gene was assessed in MSS, MSI-H, and MSI-like XLs using a reverse genetics functional approach.

Results:

XLs recapitulated the entire spectrum of colorectal cancer transcriptional subtypes. Exome and RNA-seq analyses delineated several molecular biomarkers of response and resistance to EGFR and HER2 blockade. Genotype-driven responses observed in vitro in XLs were confirmed in vivo in the matched PDXs. MSI-H models were dependent upon WRN gene expression, while loss of WRN did not affect MSS XLs growth. Interestingly, one MSS XL with transcriptional MSI-like traits was sensitive to WRN depletion.

Conclusions:

The XL platform represents a preclinical tool for functional gene validation and proof-of-concept studies to identify novel druggable vulnerabilities in colorectal cancer.