The pathological diagnosis of nerve biopsies: a practical approach

The approach to the neuropathological assessment of nerve biopsies is the main focus of this review. Nerve biopsies are invasive diagnostic procedures resulting in a permanent neurological deficit, and are therefore carried out only following an in-depth clinical assessment including laboratory, imaging, electrophysiological, and where appropriate also genetic studies. This review will outline the key diagnostic approaches and will discuss neuropathies relevant in clinical practice, caused by vasculitis, inflammatory demyelination, dysproteinaemic, amyloid, toxic agents, and neuropathies due to genetic conditions

Molecular Diagnostics of Adult Gliomas in Neuropathological Practice

This review focuses on adult gliomas, highlighting the most relevant biomarkers in the diagnosis of these tumours and the use of DNA methylation arrays to complement conventional molecular diagnostic techniques. The discovery and characterisation of diagnostic and prognostic biomarkers in brain tumours has significantly changed the neuropathological landscape over the last decade. These include mutations in the IDH1 and IDH2 genes in astrocytomas and oligodendrogliomas, histone H3 K27M mutations in midline gliomas, or BRAF mutations in a range of low-grade and high-grade glial and glioneuronal tumours. Other biomarkers of relevance are mutations in the TERT promoter, the ATRX gene, and genomic alterations such as 1p/19q codeletion, EGFR amplification, and chromosome 7 gain and 10 loss. The development of DNA methylation profiling and algorithmic classification of brain tumours has further enhanced the diagnostic abilities of neuropathologists. Methylation profiling is particularly useful for the diagnostic workup of biopsies with an inconclusive molecular test results, small samples, or samples with indistinctive low-grade or high-grade histology. This technology has become indispensable for the risk stratification of ependymal tumours, medulloblastomas and meningiomas. CONCLUSION: This review highlights the importance of an integrated approach to brain tumour diagnostics and gives a balanced view of the relevance and choice of conventional and molecular techniques in the workup of adult gliomas in diagnostic neuropathology practice

A NICMOS Direct Imaging Search for Giant Planets around the Single White Dwarfs in the Hyades

We report preliminary results from our search for massive giant planets (6-12 Jupiter masses) around the known seven single white dwarfs in the Hyades cluster at sub-arcsec separations. At an age of 625 Myr, the white dwarfs had progenitor masses of about 3 solar masses, and massive gaseous giant planets should have formed in the massive circumstellar disks around these ex-Herbig A0 stars, probably at orbital separations similar or slightly larger than that of Jupiter. Such planets would have survived the post-Main-Sequence mass loss of the parent star and would have migrated outward adiabatically to a distance of about 25 AU. At the distance of the Hyades (45 pc) this corresponds to an angular separation of 0.5 arcsec. J and H magnitudes of these giants are in the range of 20.5-23.3 mag, which can be resolved with NICMOS. The achieved sensitivities and contrast ratios agree well with simulations. Preliminary evaluation of the NICMOS data set did not reveal any evidence for neither planetary mass companions with masses down to about 10 Jupiter masses nor brown dwarfs around any of the seven white dwarfs for separations larger than 0.5 arcsec.Comment: 14th European Workshop on White Dwarf

Prion disease: experimental models and reality

The understanding of the pathogenesis and mechanisms of diseases requires a multidisciplinary approach, involving clinical observation, correlation to pathological processes, and modelling of disease mechanisms. It is an inherent challenge, and arguably impossible to generate model systems that can faithfully recapitulate all aspects of human disease. It is, therefore, important to be aware of the potentials and also the limitations of specific model systems. Model systems are usually designed to recapitulate only specific aspects of the disease, such as a pathological phenotype, a pathomechanism, or to test a hypothesis. Here, we evaluate and discuss model systems that were generated to understand clinical, pathological, genetic, biochemical, and epidemiological aspects of prion diseases. Whilst clinical research and studies on human tissue are an essential component of prion research, much of the understanding of the mechanisms governing transmission, replication, and toxicity comes from in vitro and in vivo studies. As with other neurodegenerative diseases caused by protein misfolding, the pathogenesis of prion disease is complex, full of conundra and contradictions. We will give here a historical overview of the use of models of prion disease, how they have evolved alongside the scientific questions, and how advancements in technologies have pushed the boundaries of our understanding of prion biology

Neurological update: gliomas and other primary brain tumours in adults.

The emerging understanding of molecular changes in a wide range of brain tumours has led to a significant shift in how these tumours are diagnosed, managed and treated. This article will provide a hands-on overview of the relevant biomarkers and their association with newly defined biological tumour entities

The role of prion-like mechanisms in neurodegenerative diseases

The prototype of transmissible neurodegenerative proteinopathies is prion disease, characterised by aggregation of abnormally folded conformers of the native prion protein. A wealth of mechanisms have been proposed to explain the conformational conversion from physiological protein into misfolded, pathological form, mode of toxicity, propagation from cell to cell and regional spread. There is increasing evidence that other neurodegenerative diseases, most notably Alzheimer's disease (Aβ and tau), Parkinson's disease (α-synuclein), frontotemporal dementia (TDP43, tau or FUS) and motor neurone disease (TDP43), exhibit at least some of the misfolded prion protein properties. In this review, we will discuss to what extent each of the properties of misfolded prion protein is known to occur for Aβ, tau, α-synuclein and TDP43, with particular focus on self-propagation through seeding, conformational strains, selective cellular and regional vulnerability, stability and resistance to inactivation, oligomers, toxicity and summarise the most recent literature on transmissibility of neurodegenerative disorders

Microstructure devices for water evaporation

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Evaporation of liquids is of major interest for many topics in process engineering. One of these is chemical process engineering, where evaporation of liquids and generation of superheated steam is mandatory for numerous processes. Generally, this is performed by use of classical pool boiling and evaporation process equipment, providing relatively limited performance, or by other systems like falling-film evaporators. Due to the advantages of microstructure devices especially in chemical process engineering the interest in microstructure evaporators and steam generators have been increased through the last decade. In this publication different microstructure devices used for evaporation and generation of steam will be described. Starting with simple liquid-heated devices, different types of electrically powered devices containing micro channels as well as non-channel microstructures will be shown. While evaporation of liquids in crossflow and counterflow or co-current flow micro channel devices is possible, it is, in many cases, not possible to obtain superheated steam due to certain boundary conditions. Thus, a new design was proposed to obtain complete evaporation and superheating of the generated steam

Microcystic Cerebral Neoplasm in a Nilgai Antelope (Boselaphus tragocamelus): Putative Microcystic Meningioma

Tumours of the nervous system are rare in wild and captive mammals. In this report, we describe an intracranial, solid, space-occupying lesion originating from the meninges in a Nilgai antelope (Boselaphus tragocamelus). Histologically, the tumour had a conspicuous microcystic appearance with features similar to the histological subtype of microcystic meningioma described in humans. This is the first such tumour reported in this species