Twenty-eight patients with sensory complaints of unknown etiology had repeated skin biopsies. Patients with large nerve fiber swellings on initial biopsy showed a decline in epidermal nerve fiber ...density on repeated biopsies (p < 0.05 within group; p < 0.05 vs those without swellings). Patients without nerve fiber swellings did not have changes in nerve fiber density between biopsies. Patients with large nerve fiber swellings were most likely to present clinically with paresthesias (p < 0.05).
GEM foils are known to collect charged particles on the polyimide part in its holes during the amplification process. This is accompanied by a change of the effective gain. The effect is commonly ...known as the "charge-up effect". In order to study this effect, two complementary approaches were chosen. On the one hand, the effect is studied in an iterative simulation that is based on a finite element calculation of the electrostatic environment and Garfield++ which microscopically tracks charged particles. On the other hand, a dedicated test-detector was setup with a single GEM as an amplification stage. In this study, a special focus lies on the different GEM geometries, i.e. the difference between double-conical and single-conical GEMs. A quantitative comparison between simulated and measured values will be given. It can be concluded that the typical time-constant of the gain increase is in the order of 1 × 106 initial electrons per hole. For the specific case of a single-conical GEM, it can be shown that the orientation (tapered side pointing upwards or downwards) determines whether the gain increases or decreases.
Abstract
Several governmental organizations all over the world aim for algorithmic accountability of artificial intelligence systems. However, there are few specific proposals on how exactly to ...achieve it. This article provides an extensive overview of possible transparency and inspectability mechanisms that contribute to accountability for the technical components of an algorithmic decision-making system. Following the different phases of a generic software development process, we identify and discuss several such mechanisms. For each of them, we give an estimate of the cost with respect to time and money that might be associated with that measure.
To characterize the natural history of oxaliplatin-associated neuropathy (ON) and determine whether intraepidermal nerve fiber density (IENFD) is a sensitive measure of neuropathy progression. In ...addition, we sought to assess the potential of ON as a neuroprotection model and gain insight into the relationship between axon loss and neuropathic symptoms.
Eight subjects receiving oxaliplatin for advanced colorectal cancer were prospectively followed prior to starting chemotherapy and at 30, 90, 180, and 360 days (180 days after completing treatment). Electrophysiology, punch biopsies, symptom assessment, and examinations with calculation of a reduced total neuropathy score (rTNS) were performed at each time point. Changes over time were assessed through Poisson regression for IENFD and a mixed effects model for rTNS and electrophysiology measures.
The distal leg IENFD, rTNS, peroneal, and sural amplitudes were all significantly reduced over time, while conduction velocity (peroneal and sural) and distal thigh IENFD were not. Measures of axon loss continued to worsen following discontinuation of oxaliplatin. Five of 8 subjects reported prominent symptoms associated with oxaliplatin administration.
This study demonstrates that oxaliplatin is associated with mild, sensory, and motor axon loss that may not be reversible. Axonal loss was detected by electrophysiology, rTNS, and distal leg IENFD. Several subjects reported prominent sensory symptoms that were not associated with axon loss, and that may or may not represent neuropathy. ON is an attractive paradigm for neuroprotection studies and the distal leg IENFD is an objective measure that requires minimal subject participation or study site expertise.
Thanks to the development of microscopy and confocal microscopy, diffraction-limited spot sizes are routinely achieved in spectroscopies such as fluorescence and Raman to achieve submicrometer ...spatial resolution. Because of their high numerical aperture and collection efficiency, objective lenses are also used in many applications even when a high spatial resolution is not required. In such cases, a diffraction-limited spot size is not necessary and a larger spot may in fact be preferable for a number of reasons, for example, to avoid photodamage, to perform spatial averaging, to ensure a uniform excitation profile, and so forth. In this context, we discuss here simple practical approaches to tailor the spot size with a special emphasis on obtaining large spot sizes with an objective lens. In particular, we demonstrate experimentally that Self’s formalism Self S. A. Appl. Opt. 1983, 22, 658 for the transformation of Gaussian beams provides an easy yet powerful approach to predict spot sizes in a typical laser-microscopy setup. A simple practical solution for a continuously tunable spot-size is proposed and studied. These discussions are backed up by experimental measurements in a typical Raman microscopy configuration and further illustrated by practical examples of the use of large spot sizes in the contexts of fluorescence, Raman, and surface-enhanced Raman spectroscopy.
Gaseous detectors based on large-size GEM-foils are planned to be used for a variety of upgrades and new experiments using high-rate and high-intensity particle beams. An excellent quality control of ...GEM-foils is a mandatory prerequisite to select the best foils for the assembly of a GEM detector. The high voltage stability of the foils is here of uppermost importance. In particular discharges that occur at the same position need to be detected. A spark detection system has been developed to automatically detect and record the time and position of sparks. The system is based on a commercial web camera installed in a housing for the tests and a custom-made, LabVIEW-based software for control and operation. An automatic Spark-Detection System for GEM foils was designed, built and characterized. It is able to detect and record discharges in large-size GEM foils during the quality control procedure. The spark detection e ciency was estimated to be higher than 97 %, the position resolution was determined to be approximately 0.5 mm. With this system, the characterization of GEM foils can be standardized to a much greater degree than before.
We compared the pathological changes in cutaneous axons and Schwann cells of individuals with nerve transection to the changes in patients with chronic neuropathies. Following axotomy there was ...segmentation of axons in the epidermis and dermis on the first day, and loss of axons from the skin was virtually complete by Day 11. Epidermal and small superficial dermal axons were lost before larger caliber and deeper dermal axons. Within the first 50 days following nerve transection, the denervated Schwann cells in the dermis were easily identified by their markers p75 and S100, but by 8 months they had largely disappeared. The chronic neuropathy patients had distally predominant fibre loss, with greater loss of epidermal and dermal fibres in the distal regions of the leg than proximal regions. Several patients had large axonal swellings, often alternating with axonal attenuation, even in regions with normal or nearly normal fibre densities. By electron microscopy the swellings contained accumulations of mitochondria and other particulate organelles as well as neurofilaments. These swellings are likely to represent predegenerative changes in sites of impaired axonal transport, and previous data indicate that the swellings presage fibre loss in the subsequent months. Some of the severely denervated regions had remaining Schwann cells, as judged by immunocytochemistry and by electron microscopy, but others lacked Schwann cells. By analogy with animal experiments, these regions are likely to have had more prolonged denervation. The distribution of axonal loss, the axonal swellings and the changes in Schwann cells all have implications for the design of clinical trials of agents intended to protect cutaneous innervation and to promote regeneration of cutaneous axons in peripheral neuropathies.
To explore the relationship between intraepidermal nerve fiber (IENF) density in HIV-associated sensory neuropathy (HIV-SN) to measurements of neuropathy severity and progression of HIV disease.
SN ...affects 30% of individuals with AIDS, and treatment is often ineffective. Recombinant human nerve growth factor (rhNGF) has been proposed as a trophic factor for unmyelinated nerve fibers injured in HIV-SN, and a clinical trial has recently concluded. Skin biopsy with IENF density determination has emerged as a diagnostic test for patients with small-fiber sensory neuropathy.
Sixty-two of the 270 patients with HIV-SN who participated in the trial of rhNGF were included in a substudy examining epidermal nerve fibers. IENF density was compared with neuropathic pain intensity (measured with the Gracely Pain Scale), patient and physician global pain assessments, quantitative sensory testing, CD4 counts, and plasma HIV RNA levels both at baseline and at conclusion of the placebo-controlled phase.
IENF density was inversely correlated with neuropathic pain as measured by patient (p = 0.004) and physician (p = 0.05) global pain assessments, but not using the Gracely Pain Scale. Decreased IENF density at the distal leg was associated with lower CD4 counts and higher plasma HIV RNA levels. IENF density measurements were stable over time.
IENF loss at the distal leg is associated with increased neuropathic pain, lower CD4 counts, and higher plasma viral load in HIV-SN. The robustness of the longitudinal measurement of IENF density supports its use in future longitudinal studies and clinical trials.
To explore the association between specific nucleoside reverse transcriptase inhibitors and sensory neuropathies (SNs) and define the modifying roles of hepatitis C (HCV), vitamin B12 deficiency, and ...impaired glucose tolerance.
The authors conducted a prospective cohort study of 147 HIV-infected adults at two sites chosen to emphasize demographic differences. Standardized assessments included detailed antiretroviral histories, neurologic examinations, skin biopsies for epidermal nerve quantitation, and quantitative sensory testing.
There were significant differences between subjects at Johns Hopkins University (JHU) and Monash University (MU) in gender, race, HIV transmission route, and HCV seroprevalence. Symptomatic SN was present in 49% at JHU and 55% at MU (chi2 = 4.02, p = 0.134) and was significantly more common in those at least age 40 than younger patients (odds ratio OR = 2.87, 95% CI = 1.27, 6.49). After adjusting for site, age, and CD4 cell count, exposure to didanosine (ddI) or stavudine (d4T) was associated with an significantly increased likelihood of symptomatic SN (ddI: OR = 3.21, 95% CI: 1.56, 6.60; d4T: OR = 7.66, 95% CI: 2.89, 20.33). Plasma HIV RNA, lactate, and HCV were not associated with SN. Quantitative vibratory testing identified neuropathy with a positive predictive value of 76% and epidermal nerve fiber densities 59%.
Exposure to stavudine and didanosine was significantly associated with a heightened risk for symptomatic sensory neuropathy. Reduced vibration thresholds and epidermal nerve fiber densities had the highest diagnostic efficiency of the laboratory indicators of neuropathy examined, but were relatively insensitive in isolation.
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