Use Of Spikes Research Articles

A Survey on Handling and Administration of Therapeutic Protein Products in German and Swiss Hospitals

Protein products in hospitals often have to be compounded before administration to the patient. This may comprise reconstitution of lyophilizates, dilution, storage, and transport. However, the operations for compounding and administration in the hospital may lead to changes in product quality and possibly even impact patient safety. We surveyed healthcare practitioners from three clinical units using a questionnaire and open dialogue to document common procedures and their justification and to document differences in handling procedures. The survey covered dose compounding, transportation, storage and administration. One key observation was that drug vial optimization procedures were used for some products, e.g., use of one single-use vial for several patients. This included the use of spikes and needles or closed system transfer devices (CSTDs). Filters or light protection aids were used only when specified by the manufacturer. A further observation was a different handling of the overfill in pre-filled infusion containers, possibly impacting total dose. Lastly, we documented the complexity of infusion administration setups for administration of multiple drugs. In this case, flushing procedures or the placement and use of filters in the setup vary. Our study has revealed important differences in handling and administration practice. We propose that drug developers and hospitals should collaborate to establish unified handling procedures.

Drag Reduction of a Hemispherical Body Adopting Spike at Supersonic Speed

Use of spike on a hemispherical body changes the flow field and hence the aerodynamic drag. Experimental and computational studies have been made to obtain the flow field around a hemispherical body with spikes at a supersonic Mach number of 2. The effect of shape of spike tip and length has been studied. Experiments consisted of shadowgraph flow visualisation and measurement of drag. Computations have been made adopting structured grid and k-ω turbulence model using commercial software Fluent. It is observed that use of a sharp spike itself reduces the drag significantly. However the use of a hemispherical head spike further reduces the drag. Contribution of different components towards drag indicate that the increase in length of a spike do not change the spike contribution. However the flow field on main body is altered which leads to reduction in drag with change in length. Estimated drag generally found to be higher in comparison to measured value, however the trend is almost similar.

Development and Evaluation of a Child Neurology Resident Curriculum for Communication Around Serious Illness

Background: Communication around serious illness is a core competency for all residencies. One-fifth of neurology residencies have no curriculum. Published curricula use didactics or role-play to assess confidence performing this skill without evaluation in clinical settings. The SPIKES mnemonic (Setting, Perception, Invitation, Knowledge, Empathy, Strategy/Summary) outlines 6 evidence-based steps for communication around serious illness. It is unknown whether child neurology residents can incorporate SPIKES into communication around serious illness in clinical settings. Objective: To develop and evaluate a curriculum on communication around serious illness using SPIKES for child neurology residents that shows long-term skill retention in clinical settings at a single institution. Methods: In 2019, we created a pre-post survey and skills checklist based on SPIKES, with 20 total including 10 core skills. Faculty observed residents' (n = 7) communication with families and completed both preintervention and postintervention checklists for comparison. Residents underwent training in SPIKES during a 2-hour session using didactic and coached role-play. Results: All (n = 7) residents completed preintervention surveys, 4 of 6 completed postintervention. All (n = 6) participated in the training session. Following the training, 75% of residents reported improved confidence in use of SPIKES, though 50% were still unsure about appropriately responding to emotions. There was improvement in all SPIKES skills, with significant improvement in 6 of 20 skills up to 1 year following training. Conclusion: This is the first evaluation of the implementation of a communication around serious illness curriculum for child neurology residents. We identified improved comfort with SPIKES after training. Successful acquisition and utilization of this framework in our program suggests it could be incorporated into any residency program.

A novel characterisation protocol of mechanical interactions between the ground and a tibial prosthesis for long jump

The mechanical study of Running Specific Prostheses (RSPs) is often limited to the blade. The setup developed and presented herein is a simple experiment, based on a mechanical testing machine and a camera, that assesses two indicators relevant to coaches and athletes in the field of athletics: secant stiffness and energy dissipation. The influence of four parameters on global prosthesis behaviour is evaluated: the load line offset, the prosthesis-ground angle, the sole type and the flooring type. The load line offset and the flooring type have little to no influence on their behaviour. The prosthesis-ground angle impacts the stiffness: an increase in the angle brings a significant decrease in stiffness, which strongly impacts the performance. The type of sole modifies the kinematics of the blade tip’s interaction with the ground. However, this effect is less likely to enhance the sports practice since athletics imposes the use of spikes. The camera images allow assessing the local behaviour of the sole, thus enabling to follow its strain through the compression process.

Quantization Framework for Fast Spiking Neural Networks.

Compared with artificial neural networks (ANNs), spiking neural networks (SNNs) offer additional temporal dynamics with the compromise of lower information transmission rates through the use of spikes. When using an ANN-to-SNN conversion technique there is a direct link between the activation bit precision of the artificial neurons and the time required by the spiking neurons to represent the same bit precision. This implicit link suggests that techniques used to reduce the activation bit precision of ANNs, such as quantization, can help shorten the inference latency of SNNs. However, carrying ANN quantization knowledge over to SNNs is not straightforward, as there are many fundamental differences between them. Here we propose a quantization framework for fast SNNs (QFFS) to overcome these difficulties, providing a method to build SNNs with enhanced latency and reduced loss of accuracy relative to the baseline ANN model. In this framework, we promote the compatibility of ANN information quantization techniques with SNNs, and suppress “occasional noise” to minimize accuracy loss. The resulting SNNs overcome the accuracy degeneration observed previously in SNNs with a limited number of time steps and achieve an accuracy of 70.18% on ImageNet within 8 time steps. This is the first demonstration that SNNs built by ANN-to-SNN conversion can achieve a similar latency to SNNs built by direct training.

A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC.

Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.

Training in spikes and number of training hours correlate to injury incidence in youth athletics (track and field): A prospective 52-week study

ObjectivesThe aim was to describe the annual incidence and types of musculoskeletal injuries, and to examine factors associated with injury risk. DesignA 52-week prospective study in Swedish youth athletics aged 12–15 years. MethodsData on exposure to training and injury were collected from parents/caregivers and youth athletes using a web-survey system. ResultsA total of 101 (86%) youth athletes participated. Fifty-four (53%) of the athletes reported one new injury. Girls were at higher risk of sustaining an injury than boys (p = 0.048). Ninety-one percent of the new injuries were non-traumatic and 85% occurred in the lower extremities. Injuries to the front thigh represented 20% of the injuries. Cox proportional hazard regression analyses showed a six-fold increased risk for a first injury for athletes reporting use of spikes and training <6 h every two weeks (hazard ratio, 6.1; 95% confidence interval, 1.2–31.3) compared to athletes training <6 h using no spikes. Athletes training 6 h or more reporting use or no use of spikes had an eight-fold increase injury risk (p < 0.01). ConclusionsAlmost half of the youth athletes experienced a new injury and girls had a higher risk compared to boys. Nine out of ten injuries were related to overuse. An interesting observation was the high incidence of injuries to the quadriceps muscle complex. The study identified a correlation with training hours and an interaction with track spikes and risk of injury that needs further attention.

Methodological Development of a Multi-Readout Assay for the Assessment of Antiviral Drugs against SARS-CoV-2

Currently, human infections with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are accelerating the ongoing spread of the pandemic. Several innovative types of vaccines have already been developed, whereas effective options of antiviral treatments still await a scientific implementation. The development of novel anti-SARS-CoV-2 drug candidates demands skillful strategies and analysis systems. Promising results have been achieved with first generation direct-acting antivirals targeting the viral polymerase RdRp or the protease 3CLpro. Such recently approved or investigational drugs like remdesivir and GC376 represent a basis for further development and optimization. Here, we establish a multi-readout assay (MRA) system that enables the antiviral assessment and mechanistic characterization of novel test compounds, drug repurposing and combination treatments. Our SARS-CoV-2-specific MRA combines the quantitative measurement of several parameters of virus infection, such as the intracellular production of proteins and genomes, enzymatic activities and virion release, as well as the use of reporter systems. In this regard, the antiviral efficacy of remdesivir and GC376 has been investigated in human Caco-2 cells. The readouts included the use of spike- and double-strand RNA-specific monoclonal antibodies for in-cell fluorescence imaging, a newly generated recombinant SARS-CoV-2 reporter virus d6YFP, the novel 3CLpro-based FRET CFP::YFP and the previously reported FlipGFP reporter assays, as well as viral genome-specific RT-qPCR. The data produced by our MRA confirm the high antiviral potency of these two drugs in vitro. Combined, this MRA approach may be applied for broader analyses of SARS-CoV-2-specific antivirals, including compound screenings and the characterization of selected drug candidates.

ОСОБЕННОСТИ КОНСТРУКЦИИ И ТЕХНОЛОГИИ ПЕРЕКЛЕЙНЫХ ДЕРЕВЯННЫХ КОНСТРУКТИВНЫХ ЭЛЕМЕНТОВ ДЛЯ СТОЛЯРНО-СТРОИТЕЛЬНЫХ ИЗДЕЛИЙ И МЕБЕЛИ

Each industrial enterprise, in order to increase the competitiveness of its products, must ensure such quality indicators as dimensional stability and maintainability during the entire warranty period. In practice, these indicators are ensured by observing the design rules. This problem is especially relevant in the design of joinery and construction and furniture products operated in variable climatic conditions. The purpose of the study was to establish the optimal technological chains for the production of re-adhesive structural elements; find the optimal sizes of lamellas, plots and assembly units for gluing; substantiate the expediency of veneering the glued elements with sawn veneer; design of products as a whole without the use of spikes and glue. All studies were carried out in real production conditions: at LLC Firm "Caucasian Forest", Republic of Adygea, Maikop district, settlement Tulsky and LLC HC "Mebel Chernozemya ", Voronezh. It is clear from the studies carried out that the technology of re-glued blanks allows several times to reduce warpage and increase the dimensional stability of structural elements; veneering operation allows rational use of low-grade wood in production

A study of fibre bundles’ formation regularities during the impact interaction of spikes with raw cotton particles

The article describes a study of the dynamics of interacting between loosening roller spikes and particles of raw cotton as well as the conditions for the raw cotton particles’ bundling. The process of movement of raw cotton particles was considered on the mesh surface of a fine impurity cleaner; a search was made for ways to intensify the process and to increase its stability. The conditions for imparting a rotational motion to the flyer were determined when the flyer was connected with the supplied layer of raw cotton. Turning the flyer against the axis will twist the fibre bundle that binds the particle to the rest of the cotton mass, and this is a prerequisite for the fibre to bundle. The value of the twist angle will depend on both the frictional force and the time of the force action, which together determine the energy spent on twisting. By piecewise linearization of the P ( t ) curve, the processes of shock loading and unloading of the flyer during interaction with the spike are described in good agreement with the experimental oscillograms of the process. The eccentric interaction of the spike with a particle of raw cotton was considered. The relationship of this interaction with the formation of soft defects in the fibre – bundles – was proven experimentally and theoretically. It is recommended to install spike rollers having a flat front face in the system of raw cotton pre-cleaning. The use of spikes of this shape of the front edge ensures a steady reduction in the number of bundles in the raw cotton fibre, which increases the quality of the fibre and reduces the amount of defects and impurities. As a result of the experimental and theoretical studies, data have been obtained to make it possible to organise the efficient operation of cleaning machines in the cotton ginning industry

PROBLEMS OF IODIDE IONS DETERMINATION IN MULTIVITAMINS BY INDUCTIVELY COUPLED PLASMA ATOMIC-EMISSION SPECTROMETRY

The article looks into the main problems of determination of iodine trace amounts in multivitamins by inductively coupled plasma-atomic emission spectrometry (ICP-AES), i.e. spectral overlaps attributable to macro-components, and the background effect of organic compounds. The article suggests potential ways of solving these problems. It was shown that there was a minimal overlap of iodine spectral lines by emission lines of multivitamins macro-components at the non-priority wavelength of 182.276 nm. The iodine detection limit (LOD) and limit of quantification (LOQ) were experimentally determined for ICP-AES at different wavelengths. It was demonstrated that LOD and LOQ of iodide ion were much higher in solutions containing a complex organic and multi-element matrix then in water solutions, which calls for the use of spiking in iodine assays. A comparative analysis was performed in which the content of iodine was determined in the multivitamin product Multi-tabs Junior by ICP-AES and by the reference method of inductively coupled plasma-mass spectrometry (ICP-MS). It was demonstrated that the increase in plasma power to 1500 W, the use of spiking which minimizes the background interference of organic compounds, and the use of non-priority wavelength (182.276 nm) make it possible to obtain results of iodine determination in mulitivitamins by ICP-AES which are comparable to the results obtained by the reference method.

Hypersonic Flow over Hemispherical Blunt Body with Spikes

Use of spike on a hemispherical body changes the flow fi eld and hence the aerodynamic drag. Computational studies have been made to obtain the fl ow fi eld around a hemispherical body with spikes at a hypersonic Mach number of 6. The effect of shape of spike tip and length has been studied. Laminar computations have been made adopting structured grid using commercial software Fluent. It is observed that use of a sharp spike itself reduces the drag signi cantly. However the use of a hemispherical head spike further reduces the drag. Contribution of dierent components towards drag indicate that the increase in length of a spike do not change the spike contribution. However the flow field on main body is altered which leads to reduction in dragwith change in length. Estimated maximum drag obtained is found to be highest in comparison to any reported drag value in literatures with any spike shape and length.

Dose-escalation strategies which use subgroup information.

Dose‐escalation trials commonly assume a homogeneous trial population to identify a single recommended dose of the experimental treatment for use in future trials. Wrongly assuming a homogeneous population can lead to a diluted treatment effect. Equally, exclusion of a subgroup that could in fact benefit from the treatment can cause a beneficial treatment effect to be missed. Accounting for a potential subgroup effect (ie, difference in reaction to the treatment between subgroups) in dose‐escalation can increase the chance of finding the treatment to be efficacious in a larger patient population.A standard Bayesian model‐based method of dose‐escalation is extended to account for a subgroup effect by including covariates for subgroup membership in the dose‐toxicity model. A stratified design performs well but uses available data inefficiently and makes no inferences concerning presence of a subgroup effect. A hypothesis test could potentially rectify this problem but the small sample sizes result in a low‐powered test. As an alternative, the use of spike and slab priors for variable selection is proposed. This method continually assesses the presence of a subgroup effect, enabling efficient use of the available trial data throughout escalation and in identifying the recommended dose(s). A simulation study, based on real trial data, was conducted and this design was found to be both promising and feasible.

A comparative review of variable selection techniques for covariate dependent Dirichlet process mixture models

AbstractDirichlet Process Mixture (DPM) models have been increasingly employed to specify random partition models that take into account possible patterns within covariates. Furthermore with large numbers of covariates methods for selecting the most important covariates have been proposed. Commonly the covariates are chosen either for their importance in determining the clustering of the observations or for their effect on the level of a response variable (when a regression model is specified). Typically both strategies involve the specification of latent indicators that regulate the inclusion of the covariates in the model. Common examples involve the use of spike and slab prior distributions. In this work we review the most relevant DPM models that include covariate information in the induced partition of the observations and we focus on available variable selection techniques for these models. We highlight the main features of each model and demonstrate them using simulations and a real data application. The Canadian Journal of Statistics 45: 254–273; 2017 © 2017 Statistical Society of Canada

Abstract P1-05-23: Utilities and challenges of RNA-Seq based expression and variant calling in a clinical setting

Abstract Introduction Variant calling based on DNA samples has been the gold standard of clinical testing since the advent of Sanger sequencing. The use of DNA variants has proved a great value to guide treatment in cancer patients. However, DNA based analysis will not inform about expression status of the gene harboring a particular variant. RNA has long been used to monitor expression. To this point RNA assays and analysis are confined to the research laboratory and rarely used clinically except in specifically defined gene signatures such as PAM50 and OncoType Dx. Beyond expression, RNA has the ability to confirm expression of DNA variants and identify fusion events. We hypothesize that the combination of DNA and RNA based data will allow the determination of variant specific expression status and improve clinical diagnostics. It has been previously shown that RNA sequencing (RNA-Seq) based variant calls are highly accurate and confirm DNA based variant calls. In this study we investigated the utility of RNA-Seq as a diagnostic assay integrated with DNA based sequencing data. Materials and Methods Targeted DNA sequencing of 321 genes was performed on 37 patient samples (FFPE), including 22 breast cancer samples by a commercial vendor. RNA-Seq on the same patient samples was performed using 100ng of total RNA. Libraries were run on the Illumina NextSeq 500 with a minimum of 75M paired 75bp reads. To evaluate RNA-seq expression reproducibility, replicates of 6 normal ovarian tissue samples (min. 50M reads) were run in sets of triplicates. STAR was used for alignment (hg19) and gene expression quantification (RefSeq). RNA-Seq based variant calling was performed using the SNPiR pipeline. Based on the results of the commercial assay, DNA based variants were examined for expression of the corresponding genes and ability to confirm variants in the RNA-Seq data. Results RNA expression data showed no corresponding gene expression for at least one single nucleotide variant (SNV) in 9/37 patients analyzed (24.3%). In 18/37 patients (48.6%) SNV corresponding expression was in the lowest quartile of expression values. Variant calls could be confirmed by RNA-Seq for 95/455 SNVs, with adequate coverage in 263 of the remaining 360 variant locations (median coverage: 34). Of these, a homozygous reference call was made in 166/263 SNVs. Concordance for RNA-Seq gene level expression data between replicates was &amp;gt; 0.995. Conclusions These findings suggest that RNA-Seq based data can provide clinical value when using gene expression values in combination with DNA based variant calls. We found gene level expression to be highly reproducible and will further investigate the use of spike in controls to determine clinically usable expression ranges and lower limit of expression values. To our knowledge, it has not been shown that RNA-Seq based variant calls are reproducible which is the focus of our current research as this will be one requirement for usage in a regulated environment. While our use of RNA Seq is currently limited to gene expression level data, we have demonstrated a clinically relevant benefit to using RNA Seq data as an additive feature to the current standard of DNA variant calling. Citation Format: Young B, Mark A, Meissner T, Amallraja A, Andrews A, Connolly C, Williams C, Leyland-Jones B. Utilities and challenges of RNA-Seq based expression and variant calling in a clinical setting [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-23.

The London Spikes Controversy: Homelessness, Urban Securitisation and the Question of ‘Hostile Architecture’

This article examines an ostensibly new feature of the securitised urban landscape: ‘hostile architecture’. Following controversy in 2014 London over ‘anti-homeless spikes’– metal studs implanted at ground level designed to discourage the homeless from sleeping in otherwise unrestricted spaces – certain visible methods of environmental social control were temporarily subject to intense public scrutiny and debate. While contests over public and urban spaces are not new, the spikes controversy emerged in the context of broader socio-political and governmental shifts toward neoliberal arrangements. Using the spikes issue as a case study, I contextualise hostile architecture within these broader processes and in wider patterns of urban securitisation. The article then offers an explanatory framework for understanding the controversy itself. Ultimately the article questions whether the public backlash against the use of spikes indicates genuine resistance to patterns of urban securitisation or, counterintuitively, a broader public distaste for both the homeless and the mechanisms that regulate them.

Step forward to map fully parallel energy efficient cortical columns on field programmable gate arrays

This study presents energy and area-efficient hardware architectures to map fully parallel cortical columns on reconfigurable platform – field programmable gate arrays (FPGAs). An area-efficient architecture is proposed at the system level and benchmarked with a speech recognition application. Owing to the spatio-temporal nature of spiking neurons it is more suitable to map such architectures on FPGAs where signals can be represented in binary form and communication can be performed through the use of spikes. The viability of implementing multiple recurrent neural reservoirs is demonstrated with a novel multiplier-less reconfigurable architectures and a design strategy is devised for its implementation.

EFFECT OF SPIKES INTEGRATED TO AIRFOIL AT SUPERSONIC SPEED

The objective of this is to analyse the flow field over an aerofoil section integrated with spikes at supersonic speed (Mach number greater than 1). Use of spike integrated with aerofoil changes the flow characteristics over aerofoil and hence aerodynamic lift and drag. The experiment consists of flow visualization graphs and measurement of coefficient of aerodynamic drag and lift. Here we are using different shapes of spike like sharp edge and hemi spherical edge. In this we will compare the flow over aerofoil with spike and without spike. The flow analysis is done by using Computational fluid dynamics (CFD). CFD is the study of external flow over a body or internal flow through the body. CFD is aiding aero-dynamist to better understand the flow physics and in turn to design efficient models. In short, CFD is playing a strong role as a design tool as well as a research tool.

Efficient synchronization of structurally adaptive coupled Hindmarsh–Rose neurons

The use of spikes to carry information between brain areas implies complete or partial synchronization of the neurons involved. The degree of synchronization reached by two coupled systems and the energy cost of maintaining their synchronized behavior is highly dependent on the nature of the systems. For non-identical systems the maintenance of a synchronized regime is energetically a costly process. In this work, we study conditions under which two non-identical electrically coupled neurons can reach an efficient regime of synchronization at low energy cost. We show that the energy consumption required to keep the synchronized regime can be spontaneously reduced if the receiving neuron has adaptive mechanisms able to bring its biological parameters closer in value to the corresponding ones in the sending neuron.

Metamodels for aerothermodynamic design optimization of hypersonic spiked blunt bodies

The use of spikes in the design of hypersonic vehicles yields a considerable reduction in drag and aerodynamic heating. However, their effectiveness relies strongly on the parameters of the actual designs. In this work, surrogates generated from high fidelity models are used in the context of design optimization of a spiked blunt body in hypersonic flow conditions. Four different surrogate models including a quadratic response surface and three Kriging surrogates were constructed based on the values of drag and maximum temperature responses. The evolutionary genetic algorithm is applied to find the optimum design based on each of the surrogates for these two objectives. The structure of the various surrogate models was investigated and the main differences were addressed. For the cases investigated in this work, the Kriging surrogate based on exponential correlations produced a relatively better overall performance. It was concluded that, instead of adding more training samples, eliminating some samples that show undesired aerodynamic performance yield a remarkable improvement in surrogates' performance. The optimized designs produced 92% and 13% reduction in drag and wall temperature responses, respectively.