51 research outputs found
DEVELOPMENT OF INACTIVATED POLIO VACCINE FROM ATTENUATED SABIN STRAINS FOR CLINICAL STUDIES AND TECHNOLOGY-TRANSFER PURPOSES
Recently, responding to WHOâs call for new polio vaccines, the development of Sabin-IPV (injectable, formalin-Inactivated Polio Vaccine, based on attenuated âSabinâ polio virus strains) was initated at NVI. This activity plays an important role in the WHO polio eradication strategy. The use of Sabin instead of wild-type Salk polio strains will provide additional safety during vaccine production. Initially, the Sabin-IPV production process will be based on the scale-down model of the current, and well-established, Salk-IPV process. In parallel, process development, optimization and formulation research is being carried out to further modernize the process and reduce cost per dose. The lab-scale accelerated process development, product characterization, clinical lot production, and preparations for technology transfer will be discussed.
Multivariate data analysis (MVDA) was applied on data from current IPV production (more than 60 Vero cell culture based runs) to extract relevant information, like operating ranges. Subsequently, based on the MVDA analysis, a 3-L scale-down model of the current twin 750-L bioreactors has been setup. Currently, in this lab-scale process, cell and virus culture approximate the large-scale and process improvement studies are in progress. This includes the application of increased cell densities, animal component free media, and DOE optimization in multiple parallel bioreactors.
Also, results will be shown from large-scale (to prepare for future technology transfer) generation and testing of Master- and Working virus seedlots, and clinical lot (for phase I studies) production under cGMP conditions. The obtained product was used for immunogenicity studies in rats. It was shown that Sabin-IPV induces a good immune response, and a comparison will be made to regular Salk-IPV. Finally, technology transfer to vaccine manufacturers in low and middleâincome countries will take place. For that, an international Sabin-IPV manufacturing course, including practical training at pilot-scale, is being setup
A study on prevalence and determinants of ototoxicity during treatment of childhood cancer (SOUND): protocol for a prospective study
Background: Some children with central nervous system (CNS) and solid tumors are at risk to develop ototoxicity during treatment. Up to now, several risk factors have been identified that may contribute to ototoxicity, such as platinum derivates, cranial irradiation, and brain surgery. Comedication, like antibiotics and diuretics, is known to enhance ototoxicity, but their independent influence has not been investigated in childhood cancer patients. Recommendations for hearing loss screening are missing or vary highly across treatment protocols. Additionally, adherence to existing screening guidelines is not always optimal. Currently, knowledge is lacking on the prevalence of ototoxicity. Objective: The aim of the Study on Prevalence and Determinants of Ototoxicity During Treatment of Childhood Cancer (SOUND) is to determine the feasibility of audiological testing and to determine the prevalence and determinants of ototoxicity during treatment for childhood cancer in a national cohort of patients with solid and CNS tumors.Methods: The SOUND study is a prospective cohort study in the national childhood cancer center in the Netherlands. The study aims to include all children aged 0 to 19 years with a newly diagnosed CNS or solid tumor. Part of these patients will get audiological examination as part of their standard of care (stratum 1). Patients in which audiological examination is not the standard of care will be invited for inclusion in stratum 2. Age-dependent audiological assessments will be pursued before the start of treatment and within 3 months after the end of treatment. Apart from hearing loss, we will investigate the feasibility to screen patients for tinnitus and vertigo prevalence after cancer treatment. This study will also determine the independent contribution of antibiotics and diuretics on ototoxicity. Results: This study was approved by the Medical Research Ethics Committee Utrecht (Identifier 20-417/M). Currently, we are in the process of recruitment for this study. Conclusions: The SOUND study will raise awareness about the presence of ototoxicity during the treatment of children with CNS or solid tumors. It will give insight into the prevalence and independent clinical and cotreatment-related determinants of ototoxicity. This is important for the identification of future high-risk patients. Thereby, the study will provide a basis for the selection of patients who will benefit from innovative otoprotective intervention trials during childhood cancer treatment that are currently being prepared.Analysis and Stochastic
Hematologic malignancies in pregnancy : Management guidelines from an international consensus meeting
Purpose: The incidence of hematologic malignancies during pregnancy is 0.02%. However, this figure is increasing, as women delay conception until a later age. Systemic symptoms attributed to the development of a hematologic cancermay overlapwith physiologic changes of pregnancy. A favorable prognosis is contingent upon early diagnosis and treatment. Therefore, a high index of suspicion is required by health care providers. Although timely, accurate diagnosis followed by appropriate staging is essential and should not be delayed due to pregnancy, management guidelines are lacking due to insufficient evidence-based research. Consequently, treatment is delayed, posing significant risks to maternal and fetal health, and potential pregnancy termination. This report provides guidelines for clinical management of hematologic cancers during the perinatal period, which were developed by a multidisciplinary team including an experienced hematologist/oncologist, a high-risk obstetrics specialist, a neonatologist, and experienced nurses, social workers, and psychologists. Methods: These guidelines were developed by experts in the field during the first International Consensus Meeting of PrenatalHematologicMalignancies, which took place in Leuven, Belgium, onMay 23, 2014. Results and Conclusion: This consensus summary equips health care professionals with novel diagnostic and treatment methodologies that aimfor optimal treatment of themother, while protecting fetal and pediatric health
A New Solution to the Relative Orientation Problem using only 3 Points and the Vertical Direction
This paper presents a new method to recover the relative pose between two
images, using three points and the vertical direction information. The vertical
direction can be determined in two ways: 1- using direct physical measurement
like IMU (inertial measurement unit), 2- using vertical vanishing point. This
knowledge of the vertical direction solves 2 unknowns among the 3 parameters of
the relative rotation, so that only 3 homologous points are requested to
position a couple of images. Rewriting the coplanarity equations leads to a
simpler solution. The remaining unknowns resolution is performed by an
algebraic method using Grobner bases. The elements necessary to build a
specific algebraic solver are given in this paper, allowing for a real-time
implementation. The results on real and synthetic data show the efficiency of
this method
Post-Newtonian SPH calculations of binary neutron star coalescence. I. Method and first results
We present the first results from our Post-Newtonian (PN) Smoothed Particle
Hydrodynamics (SPH) code, which has been used to study the coalescence of
binary neutron star (NS) systems. The Lagrangian particle-based code
incorporates consistently all lowest-order (1PN) relativistic effects, as well
as gravitational radiation reaction, the lowest-order dissipative term in
general relativity. We test our code on sequences of single NS models of
varying compactness, and we discuss ways to make PN simulations more relevant
to realistic NS models. We also present a PN SPH relaxation procedure for
constructing equilibrium models of synchronized binaries, and we use these
equilibrium models as initial conditions for our dynamical calculations of
binary coalescence. Though unphysical, since tidal synchronization is not
expected in NS binaries, these initial conditions allow us to compare our PN
work with previous Newtonian results.
We compare calculations with and without 1PN effects, for NS with stiff
equations of state, modeled as polytropes with . We find that 1PN
effects can play a major role in the coalescence, accelerating the final
inspiral and causing a significant misalignment in the binary just prior to
final merging. In addition, the character of the gravitational wave signal is
altered dramatically, showing strong modulation of the exponentially decaying
waveform near the end of the merger. We also discuss briefly the implications
of our results for models of gamma-ray bursts at cosmological distances.Comment: RevTeX, 37 pages, 17 figures, to appear in Phys. Rev. D, minor
corrections onl
Prevalence, risk factors, and long-term outcomes of cerebral ischemia in hospitalized COVID-19 patients - study rationale and protocol of the CORONIS study: a multicentre prospective cohort study
Background: COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown. Patients and methods: CORONavirus and Ischemic Stroke (CORONIS) is a multicentre prospective cohort study investigating the prevalence, risk factors and long-term incidence of (silent) cerebral ischemia, and the long-term functional outcome among patients with COVID-19. We aim to include 200 adult patients hospitalized with COVID-19 without symptomatic ischemic stroke to investigate the prevalence of silent cerebral ischemia compared with 60 (matched) controls with MRI. In addition, we will identify potential risk factors and/or causes of cerebral ischemia in COVID-19 patients with (n = 70) or without symptomatic stroke (n = 200) by means of blood sampling, cardiac workup and brain MRI. We will measure functional outcome and cognitive function after 3 and 12 months with standardized questionnaires in all patients with COVID-19. Finally, the long-term incidence of (new) silent cerebral ischemia in patients with COVID-19 will be assessed with follow up MRI (n = 120). The CORONIS study is designed to add further insight into the prevalence, long-term incidence and risk factors of cerebral ischemia, and the long-term functional outcome in hospitalized adult patients with COVID-19.Clinical epidemiolog
Trends in CAD-based photogrammetric measurement
In the past few decades, Computer Aided Design (CAD) systems have evolved from 2D tools that assist in construction design to the basis of software systems for a variety of applications, such as (re)design, manufacturing, quality control, and facility management. The basic functions of a modern CAD system are storage and retrieval of 3D data, their construction, manipulation, and visualisation. All these functions are needed in a photogrammetric measurement system. Therefore, photogrammetry benefits from integration with CAD, and thereby from developments in this field. There are two main interpretations of the term CAD-based photogrammetry. The first interpretation is on a system level: there is a trend towards integration of photogrammetric tools in existing CAD systems. The second interpretation is on an algorithmic level: developments in the field of CAD regarding object modelling techniques are being implemented in photogrammetric systems. In practice, the two interpretations overlap to a varying extent. The integrated photogrammetric processing of geometry and topology is defined as a minimum requirement for CAD-based photogrammetry. The paper discusses the relation between CAD and photogrammetry with an emphasis on close-range photogrammetry. Several approaches for the integration of CAD and photogrammetry are briefly reviewed, and trends in CAD-based photogrammetry are outlined. First of all, the trend towards CAD-based photogrammetry is observed. The integration of photogrammetry and CAD increases the efficiency of photogrammetric modelling. One of the reasons for this is the improvement of the user-interface, which allows better interaction with the data. A more fundamental improvement is the use of advanced object modelling techniques such as Constructive Solid Geometry, and the incorporation of geometric object constraints. Furthermore, research emphasis is on CAD-based matching techniques for automatic precise measurement of CAD-models. An overall conclusion remains: the integration of photogrammetry and CAD has great potential for widening the acceptance of photogrammetry, especially in industry. This is firstly because of the improvement in efficiency, and secondly because of the established and well-known concept of CAD
Automation in Architectural Photogrammetry: Line-Photogrammetry for the Reconstruction from Single and Multiple Images
Architectural photogrammetry has been practised for more than a century for the documentation of cultural heritage. Nowadays, the emphasis is on the construction of computer models for virtual reality applications. Since the introduction of the computer, and later the digital camera, research in photogrammetry aims at automation. This thesis reports on research on automation in architectural photogrammetry for efficient reconstruction of detailed building models from one or more, possibly widely separated, digital close-range images. This research lies on the fringes of photogrammetry and computer vision. It treats topics frequently studied in computer vision in a photogrammetric way and offers new solutions. Examples cover interior orientation and reconstruction from a single mage, vanishing point detection, and the wide-baseline stereo problem. A semi-automatic approach is chosen that exploits knowledge of the object shape, such as planarity of facades, rectangular and repeating structures in the building, and shape symmetries. Automatically or manually extracted straight image line features are the main observations in the line-photogrammetric approaches presented in this thesis. Furthermore, the methods developed are characterised by the use of robust direct solutions for approximate value computation, followed by least-squares adjustment in which the knowledge of the shape of the building is processed together with the image line observations. This integral adjustment provides optimal estimates for the object model parameters and facilitates quality assessment.Aerospace Engineerin
Astrometric satellite Hipparcos: gridstep-inconsistency correction during reduction on circles
"Hipparcosâ is the name of an astrometric satellite under development by the European Space Agency. Hipparcos is an acronym for High Precision Parallax Collecting Satellite. The aim of the Hipparcos project is to determine astrometric parameters of about 100,000 selected stars. These parameters consists of parallaxes, positions, proper motions. Hipparcos will gather other information too, like magnitudes and colour indices. The expected average accuracy is a 2 m.a.s. (milli arc second) standard deviation in position, anual proper motion and parallax. To gather the information needed to determine these astrometric parameters with such a precision, the satellite is equipped with a telescope. This telescope has two fields of view, separated by an angle of approximately 58 degrees, called the "basic angleâ. The satellite is rotating, so the two fields of view of about 1 by 1 degree scan the whole sky. The light, received from the stars passing the fields of view, is modulated by a grid. Behind the grid, photons are counted during short periods of time. In this way some 100 billion photon count measurements will be registered during the 2.5 year mission.Civil Engineering and Geoscience
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