Elevated maternal lipoprotein (a) and neonatal renal vein thrombosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Renal vein thrombosis, although rare in adults, is well recognized in neonates and is one of the most common manifestations of neonatal thromboembolic events. The etiology of renal vein thrombosis remains unidentified in the majority of cases. We report a case of renal vein thrombosis in a neonate associated with elevated maternal lipoprotein (a).</p> <p>Case presentation</p> <p>A full-term female infant, appropriate for gestational age, was born via spontaneous vaginal delivery to an 18-year-old primigravida. The infant's birth weight was 3680 g and the Apgar scores were eight and nine at 1 and 5 minutes respectively. Evaluation of the infant in the newborn nursery revealed a palpable mass in the right lumbar area. Tests revealed hematuria and a high serum creatinine level of 1.5 mg/dl. An abdominal ultrasound Doppler flow study demonstrated an enlarged right kidney, right renal vein thrombosis, and progression of the thrombosis to the inferior vena cava. There was no evidence of saggital sinus thrombosis. An extensive work-up of parents for hypercoagulable conditions was remarkable for a higher plasma lipoprotein (a) level of 73 mg/dl and an elevated fibrinogen level of 512 mg/dl in the mother. All paternal levels were normal. The plasma lipoprotein (a) level in the neonate was also normal. The neonate was treated with low molecular weight heparin (enoxaparin) at 1.5 mg/kg/day every 12 hours for 2 months, at which time a follow-up ultrasound Doppler flow study showed resolution of the thrombosis in both the renal vein and the inferior vena cava.</p> <p>Conclusion</p> <p>There have been no studies to date that have explored the effect of abnormal maternal risk factors on fetal hemostasis. A case-control study is required to investigate whether elevated levels of maternal lipoprotein (a) may be a risk factor for neonatal thrombotic processes. Although infants with this presentation are typically treated with anticoagulation, there is a lack of evidence-based guidelines. Treatment modalities vary between study and treatment centers which warrants the establishment of a national registry.</p

Persistence of Monopoly and Research Specialization

We examine the persistence of monopolies in markets with innovations when the outcome of research is uncertain. We show that for low success probabilities of research, the incumbent can seldom preempt the potential entrant. Then the efficiency effect outweighs the replacement effect. It is vice versa for high probabilities. Moreover, the incumbent specializes in safe research and the potential entrant in risky research. We also show that the probability of entry has an inverted U-shape in the success probability. Since even at the peak entry is rather unlikely, the persistence of the monopoly is high

Common Genetic Denominators for Ca++-Based Skeleton in Metazoa: Role of Osteoclast-Stimulating Factor and of Carbonic Anhydrase in a Calcareous Sponge

Calcium-based matrices serve predominantly as inorganic, hard skeletal systems in Metazoa from calcareous sponges [phylum Porifera; class Calcarea] to proto- and deuterostomian multicellular animals. The calcareous sponges form their skeletal elements, the spicules, from amorphous calcium carbonate (ACC). Treatment of spicules from Sycon raphanus with sodium hypochlorite (NaOCl) results in the disintegration of the ACC in those skeletal elements. Until now a distinct protein/enzyme involved in ACC metabolism could not been identified in those animals. We applied the technique of phage display combinatorial libraries to identify oligopeptides that bind to NaOCl-treated spicules: those oligopeptides allowed us to detect proteins that bind to those spicules. Two molecules have been identified, the (putative) enzyme carbonic anhydrase and the (putative) osteoclast-stimulating factor (OSTF), that are involved in the catabolism of ACC. The complete cDNAs were isolated and the recombinant proteins were prepared to raise antibodies. In turn, immunofluorescence staining of tissue slices and qPCR analyses have been performed. The data show that sponges, cultivated under standard condition (10 mM CaCl2) show low levels of transcripts/proteins for carbonic anhydrase or OSTF, compared to those animals that had been cultivated under Ca2+-depletion condition (1 mM CaCl2). Our data identify with the carbonic anhydrase and the OSTF the first two molecules which remain conserved in cells, potentially involved in Ca-based skeletal dissolution, from sponges (sclerocytes) to human (osteoclast)

A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40

BACKGROUND: Mantle cell lymphoma (MCL) is a distinct clinical pathologic subtype of B cell non-Hodgkin’s lymphoma often associated with poor prognosis. New therapeutic approaches based on boosting anti-tumor immunity are needed. MCL is associated with overexpression of cyclin D1 thus rendering this molecule an interesting target for immunotherapy. METHODS: We show here a novel strategy for the development of recombinant vaccines carrying cyclin D1 cancer antigens that can be targeted to dendritic cells (DCs) via CD40. RESULTS: Healthy individuals and MCL patients have a broad repertoire of cyclin D1-specific CD4(+) and CD8(+) T cells. Cyclin D1-specific T cells secrete IFN-γ. DCs loaded with whole tumor cells or with selected peptides can elicit cyclin D1-specific CD8(+) T cells that kill MCL tumor cells. We developed a recombinant vaccine based on targeting cyclin D1 antigen to human DCs via an anti-CD40 mAb. Targeting monocyte-derived human DCs in vitro with anti-CD40-cyclin D1 fusion protein expanded a broad repertoire of cyclin D1-specific CD4(+) and CD8(+) T cells. CONCLUSIONS: This study demonstrated that cyclin D1 represents a good target for immunotherapy and targeting cyclin D1 to DCs provides a new strategy for mantle cell lymphoma vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-015-0131-7) contains supplementary material, which is available to authorized users

Systematic investigation of geometrical parameters’ influence on the appearance of surface deflections in sheet metal forming

Surface deflections occur during springback, which follows deep drawing. They highly affect the visual appearance of outer skin components and are, therefore, undesirable. In this work, the influence of the part geometry on the shaping of surface deflections is investigated. The geometrical parameters of an exemplary component are varied and existing surface deflections are detected. For this, a component consisting of a multiple curved surface with an inserted door handle hollow is used, and AA6016, with a sheet thickness of 1.0 mm, as well as DC06, with a sheet thickness of 0.7 mm, are chosen. After the simulations are performed in AutoForm plus R6TM, a virtual stone, Three-Point Gauging and the analysis of curvatures of the part before and after springback are used to detect surface deflections

FEA-based Development of a New Tool for Systematic Experimental Validation of Nonlinear Strain Paths and Design of Test Specimens

To achieve high accuracy in finite element simulation, it is beneficial to model forming limit curves (FLCs) for nonlinear strain paths, since FLCs based on linear strain paths inaccurately predict the failure of parts that undergo nonlinear strain paths. Standardized Nakajima or Marciniak tests are used to create a FLC for linear strain paths. For common strain paths, the shapes of the specimens are well-known. Only a limited set of nonlinear strain paths can be generated by using these tests. For example, a biaxial strain path can be generated, and then the test specimen can be cut to generate a uniaxial strain path. However, the other way around is not possible. Therefore, it is important to develop a new tool that can systematically investigate all kinds of nonlinear strain paths. This paper describes a newly developed deep drawing tool that exhibits these properties. Large specimens with homogeneous strain in the centre can be generated for any strain state. These specimens are sufficiently large that a second test specimen can be cut out to generate another strain path using Nakajima or Marciniak tests. The shape of blank for uniaxial, plane and biaxial strains are presented and analysed both numerically and experimentally. A nonlinear strain path consisting of a uniaxial strain path followed by a biaxial strain path is shown as an example

Experimental Validation of Detecting Surface Deflections on Sheet Metal Parts with LS-Dyna

The appearance of surface deflections on sheet metal parts is undesirable. When surface deflections are detected on a sheet metal part during tryout, the tool geometry has to be modified. This procedure is performed at a later stage of the product development process which leads to high costs and effort. Therefore, it is useful to detect surface deflections before the actual production in the finite element simulation. Then, it is much easier to modify the tool geometry in such a way that surface deflections don’t occur any more

Characterization of a Computational Fluid Dynamics Thermocouple Model Subjected to Stochastic Environmental Forcing Using Moment Based Analysis

With increasing requirements for model validation when comparing computational and experimental results, there is a need to incorporate detailed representations of measurement devices within the computational simulations. Thermocouples are the most common temperature measurement transducers in flames and fire environments. Even for the relatively simple thermocouple transducer, the coupling of heat transfer mechanisms particularly under unsteady flow conditions leads to interesting dynamics. As experimentalists are well aware, the experimentally determined thermocouple values are not the same as the local gas temperatures and corrections are often required. From the computational perspective, it is improper then to assume that the predicted gas temperatures should be the same as the temperatures that an experimentalist might measure since the thermal characteristics of the thermocouple influence the indicated temperature. The thermal characteristics of simulated thermocouples in unsteady flame conditions are investigated. Validation exercises are presented to test the underlying thermocouple model. The thermocouple model problem is examined for a quasi-steady problem in which the gas temperature and surrounding walls are assumed to be random and described by probability density functions (PDFs). Differences are noted between the predicted thermocouple response and expected response. These differences are interpreted from the perspective of what modeling artifacts might drive the differences