The advantages of backthinning monolithic active pixel sensors (MAPS) based on complementary metal oxide semiconductor (CMOS) direct electron detectors for electron microscopy have been discussed ...previously; they include better spatial resolution (modulation transfer function or MTF) and efficiency at all spatial frequencies (detective quantum efficiency or DQE). It was suggested that a ‘thin’ CMOS detector would have the most outstanding properties 1–3 because of a reduction in the proportion of backscattered electrons. In this paper we show, theoretically (using Monte Carlo simulations of electron trajectories) and experimentally that this is indeed the case.
The modulation transfer functions of prototype backthinned CMOS direct electron detectors have been measured at 300keV. At zero spatial frequency, in non-backthinned 700-μm-thick detectors, the backscattered component makes up over 40% of the total signal but, by backthinning to 100, 50 or 35μm, this can be reduced to 25%, 15% and 10%, respectively. For the 35μm backthinned detector, this reduction in backscatter increases the MTF by 40% for spatial frequencies between 0.1 and 1.0 Nyquist. As discussed in the main text, reducing backscattering in backthinned detectors should also improve DQE.
Vogt–Koyanagi–Harada syndrome Greco, A; Fusconi, M; Gallo, A ...
Autoimmunity reviews,
09/2013, Letnik:
12, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Abstract Objectives The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt–Koyanagi–Harada syndrome, including viral infection, genetic factors and ...immunomediated mechanisms, and to discuss pathogenesis and its relevance to pharmacotherapy. Systematic review methodology Relevant publications from 1965 to 2012 on the aetiopathogenesis and pharmacotherapy of VKHS were analysed. Results and conclusion Vogt–Koyanagi–Harada syndrome (VKHS) is a rare multisystemic autoimmune disease that affects tissues containing melanin, including the eye, inner ear, meninges, and skin. The disease is characterised by bilateral uveitis associated with a varying constellation of auditory, neurological and cutaneous manifestations. The disease occurs more frequently among people with darker skin pigmentation. Asians, Native Americans, and Hispanics are most frequently affected. It predominates in patients aged between 20 and 50 years, and females are affected more frequently, with a female:male ratio of 2:1. The classic clinical course is characterised by bilateral panuveitis, hypoacusis, and meningitis, in addition to cutaneous involvement with poliosis, vitiligo, and alopecia. Although the exact cause of VKH disease remains unknown, it is thought to be a T-cell-mediated autoimmune process directed against melanocytes. VKHS classically begins with vague systemic symptoms suggestive of a viral infection, although a clear association between a specific viral agent and the disease has not been established. Genetic factors may play an important role in the loss of self-tolerance in VKHS. The HLA-DRB1*0405 allele is the main susceptibility allele for VKHS. Early and aggressive systemic corticosteroids are still the primary initial therapy for VKHS. Ocular complications may require an intravitreous injection of corticosteroids. Despite proper treatment with steroids, a number of patients experience recurrent attacks or steroid-associated complications. Thus, non steroid immunomodulatory therapy (IMT) has become necessary for the treatment of VKHS.
We compare the direct electron imaging performance at 120keV of a monolithic active pixel sensor (MAPS) operated in a conventional integrating mode with the performance obtained when operated in a ...single event counting mode. For the combination of sensor and incident electron energy used here, we propose a heuristic approach with which to process the single event images in which each event is renormalised to have an integrated weight of unity. Using this approach we find enhancements in the Nyquist frequency modulation transfer function (MTF) and detective quantum efficiency (DQE) over the corresponding integrating mode values by factors of 8 and 3, respectively.
The knowledge of mechanisms responsible for acquired sensorineural hearing loss in children, such as viral and bacterial infections, noise exposure, aminoglycoside and cisplatin ototoxicity, is ...increasing and progressively changing the clinical management of affected patients. Viral infections are by far the most relevant cause of acquired hearing loss, followed by aminoglycoside and platinum derivative ototoxicity; moreover, cochlear damage induced by noise overexposure, mainly in adolescents, is an emerging topic. Pharmacological approaches are still challenging to develop a truly effective cochlear protection; however, the use of steroids, antioxidants, antiviral drugs and other small molecules is encouraging for clinical practice. Most of evidence on the effectiveness of antioxidants is still limited to experimental models, while the use of corticosteroids and antiviral drugs has a wide correspondence in literature but with controversial safety. Future therapeutic perspectives include innovative strategies to transport drugs into the cochlea, such as molecules incorporated in nanoparticles that can be delivered to a specific target. Innovative approaches also include the gene therapy designed to compensate for abnormal genes or to make proteins by introducing genetic material into cells; finally, regenerative medicine (including stem cell approaches) may play a central role in the upcoming years in hearing preservation and restoration even if its role in the inner ear is still debated.
Abstract Objectives The objective of our study was to review our current knowledge of the aetiopathogenesis of Cogan's syndrome, including viral infection and autoimmunity, and to discuss disease ...pathogenesis with relevance to pharmacotherapy. Systematic review methodology Relevant publications on the aetiopathogenesis and pharmacotherapy of Cogan's syndrome from 1945 to 2012 were analysed. Results and conclusions Cogan's syndrome is a rare autoimmune vasculitis, and its pathogenesis is unknown. Infection, but primarily autoimmunity, may play contributing roles in the pathogenesis of this disease. It is characterised by ocular and audiovestibular symptoms similar to those of Meniere's syndrome. Approximately 70% of patients have systemic disease, of which vasculitis is considered the pathological mechanism. The immunologic theory is based on the release of auto-antibodies against corneal, inner ear and endothelial antigens, and of anti-nuclear cytoplasmic auto-antibodies (ANCA). Corticosteroids are the first line of treatment, and multiple immunosuppressive drugs have been tried with varying degrees of success. Tumour necrosis factor (TNF)-alpha blockers are a category of immunosuppressive agents representing a recent novel therapeutic option in Cogan's syndrome.
The present work on drug-induced ototoxicity, tinnitus and vertigo represents the update and revision of a previous guide to adverse drug reactions for italian physicians (2005). The panorama of ...drug-induced side effects causing ototoxicity or symptoms such as tinnitus or dizziness and vertigo has enlarged in recent years, thanks to a better knowledge and a more specific attention of pharmaceutical firms and drug-control institutions. In daily clinical practice, there is a need for the family physician and the ENT specialist or audiologist (also in consideration of the possible medico-legal implications) to focus the attention on the possible risk of otological side effects. This would allow a clinical risk-benefit evaluation, weighing the possible clinical advantage in their field of competence against possible otological side-effects. The list of active ingredients and drugs is subdivided in categories based on their audiological and otoneurological side-effects, that have been signaled by the drug companies and/or ministerial notes. Drugs have also been subcategorized with regards to the field in which they are applied, the therapeutic indications and the clinical behaviour. They have also been organized in alphabetical order, for an easier consultation. The guide above, even if initially conceived for being used in Italy, also presents a more general and international interest, expecially as for as the concepts of pharmacology and the features of the active ingredients are concerned. The guide is, therefore, useful as for as we are concerned to any physician, regardless of the country he/she operates in.
The APV25 is a 128-channel analogue pipeline chip for the readout of silicon microstrip detectors in the CMS tracker at the LHC. Each channel comprises a low noise amplifier, a 192-cell analogue ...pipeline and a deconvolution readout circuit. Output data are transmitted on a single differential current output via an analogue multiplexer. The chip is fabricated in a standard 0.25
μm CMOS process to take advantage of the radiation tolerance, lower noise and power, and high circuit density. Experimental characterisation of this circuit shows full functionality and good performance both in pre- and post-irradiation (20
Mrad) conditions. The measured noise is significantly reduced compared to earlier APV versions. A description of the design and results from measurements prior to irradiation are presented.
This paper reports on the development and commissioning of the GP2 detector. GP2 was developed to address the requirement for a high-resolution event-mode imaging detector, for application in ...energy-resolved neutron radiography. The name GP2 derives from the use of gadolinium as a neutron conversion material, combined with a second-generation mass spectrometry sensor known as PImMS2. Theoretical and measured characteristics of GP2 are compared, with emphasis on the usability and functionality of the detector. The development of the detector has been steered by a design philosophy which was established to ensure that the detector has unique and novel impact. The motivation and consequences of the design philosophy are discussed. The key parameters reported are the neutron detection efficiency (7.5% at 2.5 Å), gamma sensitivity (1.5 × 10 -3 ), and a spatial resolution (modulation transfer function at 10%) of 6.4 lp/mm for a 4-μm-thick natural gadolinium neutron converter film.
Cancer stem cells (CSCs) are a group of cells with eternal life or infinite self-renewal ability, which have high migrating, infiltrative, and metastatic abilities. Though CSCs only account for a ...small proportion in tumors, the high resistance to traditional therapy exempts them from therapy killing and thus they can reconstruct tumors. Previous studies found that heterogeneity of cancer cells extensively exists in head and neck cancers. Our current knowledge, about CSCs in the laryngeal cancer (LC), largely depends on head and neck studies. Given the lack of systematic data about CSCs in LC, we propose a review of the literature, reporting the evidences of CSCs in tumorigenesis of LC, with the purpose to provide new insights into the prevention and/or treatment of laryngeal carcinoma.
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