High seroprevalence of human herpes virus 8 (HHV-8) antibodies among vertically HIV-infected pediatric patients living in Germany

Background: Human herpes virus 8 (HHV-8), a gamma herpes virus, is the etiological agent for Kaposi sarcoma (KS). HIV-infected adults with advanced immunodeficiency are at risk. Prevalence data of HHV-8 infection in HIV-infected children living in non-endemic areas are limited. Serologic studies indicate low seroprevalence rates of 3–4% for healthy children living in United States and Germany [1]. Purpose of the study: The aim of the study was to determine the seroprevalence of HHV-8 antibodies among vertically HIV-infected pediatric patients in Germany and to evaluate their association with age, gender, ethnicity, and other demographic factors. Methods: In 2012, a multi-center cross-sectional study was conducted in four University Hospitals in Germany. Stored frozen serum specimens obtained from vertically HIV-infected children and adolescents were tested for antibodies against lytic and latent HHV-8 antigens. Data on patients' demographic characteristics and medical history were recorded. Results: A total of 214 HIV-infected children and adolescents (105 males, 109 females) were included. The median age was 10.2 years (range 1 months–22.6 years). A high proportion of these children (62%) was born in Western Europe, whereas 65% (139/214) of their mothers were born in countries outside Western Europe. The majoritiy (91%) of the children had been treated with highly active antiretroviral therapy and 55.2% (116/210) had a HIV-viral load<50 copies/mL. The median CD4 cell count was 1000/L (range 3–4400). The overall seroprevalence of HHV-8 antibodies was 23.8% (51/214). Seroprevalence rates did not show significant differences between age or gender. In the group of young children aged 1 month to 35 months, 19.4% (46/31) had HHV-8 antibodies, compared to 25% (25/100) in children aged 36 months to 11 years, and 24.1% (20/83) children 12 years and older. In the study group, seroprevalence rates were significantly lower in children who were born in Western Europe (p <0.01) compared to those born in Africa, Asia, or Eastern Europe. Clinical symptoms of HHV-8 infection were reported to be uncommon; only one child had a history of KS at 2 years of age. Conclusions: Vertically HIV-infected pediatric patients living in Germany showed a high HHV-8 seroprevalence of 23.8%. These rates were higher as expected in the normal pediatric population. The findings suggest that HHV-8 infection occurred already in the first years of life

Melanoma of the middle ear: initial presentation, Fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography imaging and follow up

Abstract Background: We present a rare case of primary mucosal melanoma of the middle ear imaged with 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). Method: Clinical, radiological, intra-operative and histological findings are discussed. Results: An 88-year-old woman presented with intermittent otorrhoea of the left ear for several months. Otoscopy revealed a livid protrusion of the tympanic membrane. Melanoma was not suspected initially, but was established on transmembranous biopsy. Pre-operative 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography revealed a mass lesion in the left tympanic cavity with high fluoro-deoxyglucose uptake, as well as an ipsilateral intraparotid lymph node metastasis. The patient underwent surgical treatment. The diagnosis of melanoma was confirmed histologically. Conclusion: In this rare case, clinical, radiological and surgical findings led to the diagnosis of a primary mucosal melanoma of the middle ea

Development and operation of a pixel segmented liquid-filled linear array for radiotherapy quality assurance

A liquid isooctane (C$_{8}$H$_{18}$) filled ionization linear array for radiotherapy quality assurance has been designed, built and tested. The detector consists of 128 pixels, each of them with an area of 1.7 mm $\times$ 1.7 mm and a gap of 0.5 mm. The small pixel size makes the detector ideal for high gradient beam profiles like those present in Intensity Modulated Radiation Therapy (IMRT) and radiosurgery. As read-out electronics we use the X-Ray Data Acquisition System (XDAS) with the Xchip developed by the CCLRC. Studies concerning the collection efficiency dependence on the polarization voltage and on the dose rate have been made in order to optimize the device operation. In the first tests we have studied dose rate and energy dependences, and signal reproducibility. Dose rate dependence was found lower than 2.5 % up to 5 Gy min$^{-1}$, and energy dependence lower than 2.1 % up to 20 cm depth in solid water. Output factors and penumbras for several rectangular fields have been measured with the linear array and were compared with the results obtained with a 0.125 cm$^{3}$ air ionization chamber and radiographic film, respectively. Finally, we have acquired profiles for an IMRT field and for a virtual wedge. These profiles have also been compared with radiographic film measurements. All the comparisons show a good correspondence. Signal reproducibility was within a 2% during the test period (around three months). The device has proved its capability to verify on-line therapy beams with good spatial resolution and signal to noise ratio.Comment: 16 pages, 12 figures Submitted to Phys. Med. Bio

The lysine methyltransferase SMYD3 interacts with hepatitis C virus NS5A and is a negative regulator of viral particle production

Hepatitis C virus (HCV) is a considerable global health and economic burden. The HCV nonstructural protein (NS) 5A is essential for the viral life cycle. The ability of NS5A to interact with different host and viral proteins allow it to manipulate cellular pathways and regulate viral processes, including RNA replication and virus particle assembly. As part of a proteomic screen, we identified several NS5A-binding proteins, including the lysine methyltransferase SET and MYND domain containing protein 3 (SMYD3). We confirmed the interaction in the context of viral replication by co-immunoprecipitation and co-localization studies. Mutational analyses revealed that the MYND-domain of SMYD3 and domain III of NS5A are required for the interaction. Overexpression of SMYD3 resulted in decreased intracellular and extracellular virus titers, whilst viral RNA replication remained unchanged, suggesting that SMYD3 negatively affects HCV particle production in a NS5A-dependent manner. (C) 2014 The Authors. Published by Elsevier Inc

Pareto Optimization of a Laser Wakefield Accelerator

Optimization of accelerator performance parameters is limited by numerous trade-offs and finding the appropriate balance between optimization goals for an unknown system is challenging to achieve. Here we show that multi-objective Bayesian optimization can map the solution space of a laser wakefield accelerator in a very sample-efficient way. Using a Gaussian mixture model, we isolate contributions related to an electron bunch at a certain energy and we observe that there exists a wide range of Pareto-optimal solutions that trade beam energy versus charge at similar laser-to-beam efficiency. However, many applications such as light sources require particle beams at a certain target energy. Once such a constraint is introduced we observe a direct trade-off between energy spread and accelerator efficiency. We furthermore demonstrate how specific solutions can be exploited using \emph{a posteriori} scalarization of the objectives, thereby efficiently splitting the exploration and exploitation phases

Quantum Zeno Effect and Light-Dark Periods for a Single Atom

The quantum Zeno effect (QZE) predicts a slow-down of the time development of a system under rapidly repeated ideal measurements, and experimentally this was tested for an ensemble of atoms using short laser pulses for non-selective state measurements. Here we consider such pulses for selective measurements on a single system. Each probe pulse will cause a burst of fluorescence or no fluorescence. If the probe pulses were strictly ideal measurements, the QZE would predict periods of fluorescence bursts alternating with periods of no fluorescence (light and dark periods) which would become longer and longer with increasing frequency of the measurements. The non-ideal character of the measurements is taken into account by incorporating the laser pulses in the interaction, and this is used to determine the corrections to the ideal case. In the limit, when the time between the laser pulses goes to zero, no freezing occurs but instead we show convergence to the familiar macroscopic light and dark periods of the continuously driven Dehmelt system. An experiment of this type should be feasible for a single atom or ion in a trapComment: 16 pages, LaTeX, a4.sty; to appear in J. Phys.