Application of the New Classification on Patients with a Disorder of Sex Development in Indonesia

Disorder of sex development (DSD) patients in Indonesia most often do not receive a proper diagnostic evaluation and treatment. This study intended to categorize 88 Indonesian patients in accordance with the new consensus DSD algorithm. Diagnostic evaluation including clinical, hormonal, genetic, imaging, surgical, and histological parameters was performed. Fifty-three patients were raised as males, and 34 as females. Of 22 patients with 46, XX DSD, 15 had congenital adrenal hyperplasia, while in one patient, an ovarian Leydig cell tumor was found. In all 58 46, XY DSD patients, 29 were suspected of a disorder of androgen action (12 with an androgen receptor mutation), and in 9, gonadal dysgenesis was found and, in 20, severe hypospadias e.c.i. Implementation of the current consensus statement in a resource-poor environment is very difficult. The aim of the diagnostic workup in developing countries should be to end up with an evidence-based diagnosis. This is essential to improve treatment and thereby to improve the patients' quality of life

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype

Mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo syndrome type B) is a lysosomal storage disorder caused by deficiency of the enzyme N-acetyl-α-D-glucosaminidase (NAGLU). Information on the natural course of MPS IIIB is scarce but much needed in view of emerging therapies. To improve knowledge on the natural course, data on all 52 MPS IIIB patients ever identified by enzymatic studies in the Netherlands were gathered. Clinical data on 44 patients could be retrieved. Only a small number (n = 9; 21%) presented with a classical MPS III phenotype; all other patients showed a much more attenuated course of the disease characterized by a significantly slower regression of intellectual and motor abilities. The majority of patients lived well into adulthood. First signs of the disease, usually mild developmental delay, were observed at a median age of 4 years. Subsequently, patients showed a slowing and eventually a stagnation of development. Patients with the attenuated phenotype had a stable intellectual disability for many years. Molecular analysis was performed in 24 index patients. The missense changes p.R643C, p.S612G, p.E634K, and p.L497V were exclusively found in patients with the attenuated phenotype. MPS IIIB comprises a remarkably wide spectrum of disease severity, and an unselected cohort including all Dutch patients showed a large proportion (79%) with an attenuated phenotype. MPS IIIB must be considered in patients with a developmental delay, even in the absence of a progressive decline in intellectual abilities. A key feature, necessitating metabolic studies, is the coexistence of behavioral problems

The genetic diagnosis of rare endocrine disorders of sex development and maturation : a survey among Endo-ERN centres

Differences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries. All HCPs, except 1, performed NGS investigations for SDM disorders on 6720 patients, 3764 (56%) with differences of sex development (DSD), including 811 unexplained primary ovarian insufficiency, and 2956 (44%) with congenital hypogonadotropic hypogonadism (CHH). The approaches varied from targeted analysis of custom gene panels (range: 11-490 genes) in 81.5% of cases or whole exome sequencing with the extraction of a virtual panel in the remaining cases. These analyses were performed for diagnostic purposes in 21 HCPs, supported by the National Health Systems in 16 cases. The likelihood of finding a variant ranged between 7 and 60%, mainly depending upon the number of analysed genes or criteria used for reporting, most HCPs also reporting variants of uncertain significance. These data illustrate the status of genetic diagnosis of DSD and CHH across Europe. In most countries, these analyses are performed for diagnostic purposes, yielding highly variable results, thus suggesting the need for harmonization and general improvements of NGS approaches.publishersversionPeer reviewe

Design and implementation of a three-layer cognitive radar architecture

In the paper we describe a novel concept for an integrated cognitive radar architecture developed at Fraunhofer FHR that is based on the Rasmussen model of human performance and incorporates ideas from three-layer robotic control architectures. We give simulative and experimental examples for cognitive radar behavior generated on each of the three abstraction layers

Polarimetric radar technology for european defence superiority - The polrad project

The benefits of polarimetric radar technologies are addressed and respective technology gaps are identified for a variety of applications in radar and electronic warfare. Examples of fully polarimetric data processing are provided for FOPEN applications on real data, making use of Polarimetric Whitening Filtering (PWF) with subsequent Polarimetric Matched Filter (PMF) techniques as well as for Polarimetric Space Time Adaptive Processing (Pol-STAP) on simulated data. The performance advantages of these polarimetric approaches are demonstrated and compared with classical processing schemes. Part of these results were elaborated within the framework of the PolRad project, funded by the European Defence Agency (EDA), with the aim to demonstrate the benefits of polarimetric radar technology in defence scenarios for target classification, target detection and tracking of man-made object in vegetated environment as well as for the usability for Electronic Support Measures. Finally in this context a potential outlook is given in terms of technology and timelines for polarimetric applications

Nonparametric ISAR autofocusing via entropy-based doppler centroid search

A novel approach to nonparametric entropy-based autofocusing of inverse synthetic aperture radar images is proposed. Kinematics considerations show that the range cell corresponding to the target rotation center has a purely translational Doppler phase. This range cell can be selected by means of entropy criteria, and its phase component used as a measurement of the translational Doppler phase. Concerning the existing techniques, the new one is robust enough to noise and low target reflectivity, whereas provides higher quality output images with low computational load. The quality of the output is further confirmed by resorting to a recently published automatic target recognition algorithm, obtaining a very high success rate on a wide and variegated data set, acquired by the tracking and imaging radar system of the Fraunhofer FHR Institute

Results on Super-Resolution and Target Identification Techniques from the SPERI Project

We give an overview of the EDA CAT B R&D project Signal Processing for Enhanced Radar Imaging (SPERI). In this project, the benefits of applying two super-resolution methods Super Spatially Variant Apodization (SSVA) and Compressed Sensing (CS) to two-dimensional Inverse Synthetic Aperture Radar (ISAR) images of airborne radar targets were investigated with respect to the improvements in automatic target identification rates. The algorithms have been tested over a database of more than 1200 real radar images