Detailed analysis of allergic cutaneous reactions to spinal cord stimulator devices

The use of spinal cord stimulation (SCS) devices to treat chronic, refractory neuropathic pain continues to expand in application. While device-related complications have been well described, inflammatory reactions to the components of these devices remain underreported. In contrast, hypersensitivity reactions associated with other implanted therapies, such as endovascular and cardiac rhythm devices, have been detailed. The purpose of this case series is to describe the clinical presentation and course of inflammatory reactions as well as the histology of these reactions. All patients required removal of the entire device after developing inflammatory reactions over a time course of 1–3 months. Two patients developed a foreign body reaction in the lead insertion wound as well as at the implantable pulse generator site, with histology positive for giant cells. One patient developed an inflammatory dermatitis on the flank and abdomen that resolved with topical hydrocortisone. “In vivo” testing with a lead extension fragment placed in the buttock resulted in a negative reaction followed by successful reimplantation of an SCS device. Inflammatory reactions to SCS devices can manifest as contact dermatitis, granuloma formation, or foreign body reactions with giant cell formation. Tissue diagnosis is essential, and is helpful to differentiate an inflammatory reaction from infection. The role of skin patch testing for 96 hours may not be suited to detect inflammatory giant cell reactions that manifest several weeks post implantation

Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels

The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.Comment: 24 pages, including 6 figures, published in 200

The origin of green icebergs in Antarctica

A comparison of samples from a translucent green iceberg with a core from the Ronne Ice Shelf revealed an excellent agreement in isotopic composition, crystal structure, and incorporated sediment particles. Marine shelf ice which constitutes the basal portion of some ice shelves is considered to be the source of green icebergs. It most likely results from "ice pump" processes which produce large amounts of ice platelets in the water column beneath ice shelves. These subsequently accumulate and become compacted into bubble-free, desalinated ice. Iceberg and drift-buoy trajectories indicate that green icebergs observed in the Weddell Sea originate from the Amery Ice Shelf rather than from the Ronne Ice Shelf, although the latter ice shelf is also a potential source

Effect of thermal phase fluctuations on the superfluid density of two-dimensional superconducting films

High precision measurements of the complex sheet conductivity of superconducting Mo77Ge23 thin films have been made from 0.4 K through Tc. A sharp drop in the inverse sheet inductance, 1/L(T), is observed at a temperature, Tc, which lies below the mean-field transition temperature, Tco. Just below Tc, the suppression of 1/L(T) below its mean-field value indicates that longitudinal phase fluctuations have nearly their full classical amplitude, but they disappear rapidly as T decreases. We argue that there is a quantum crossover at about 0.94 Tco, below which classical phase fluctuations are suppressed.Comment: 14 pages, 3 figures. Subm. to PR

A life story in three parts: the use of triptychs to make sense of personal digital data

Many social media platforms support the curation of personal digital data, and, more recently, the use of that data for review and reflection. We explored the process of reflection by asking users to create a meaningful ‘triptych’ of photographs drawn from their Facebook accounts. In a first study, we asked participants to manually trawl their own accounts and select three relevant images, which we then framed and used as an interview probe. In a second study, we designed an automated triptych generation system and assessed participants’ experiences of using this system. We conducted qualitative analyses of participant interviews from both studies. Consistent with other ‘slow technology’ work, we found the act of creating a physical artefact from social media data gave that data new meaning, albeit with notable differences between manual vs automatically generated triptychs. We conclude by discussing possible improvements to the design of the automated triptych system

International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

Remifentanil in the Horse: Identification and Detection of its Major Urinary Metabolite

Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phyenylamino]-1- piperidinepropionic acid methyl ester) is a μ-opioid receptor agonist with considerable abuse potential in racing horses. The identification of its major equine urinary metabolite, 4-methoxycarbonyl-4-[(1- oxopropyl)phenylamino]-1-piperidinepropionic acid, an ester hydrolysis product of remifentanil is reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear-cut locomotor responses, establishing the clinical efficacy of this dose. ELISA analysis of postadministration urine samples readily detected fentanyl equivalents in these samples. Mass spectrometric analysis, using solid-phase extraction and trimethylsilyl (TMS) derivatization, showed the urine samples contained parent remifentanil in low concentrations, peaking at 1 h. More significantly, a major peak was identified as representing 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1- piperidinepropionic acid, arising from ester hydrolysis of remifentanil. This metabolite reached its maximal urinary concentrations at 1 h and was present at up to 10-fold greater concentrations than parent remifentanil. Base hydrolysis of remifentanil yielded a carboxylic acid with the same mass spectral characteristics as those of the equine metabolite. In summary, these data indicate that remifentanil administration results in the appearance of readily detectable amounts of 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]- 1-piperidinepropionic acid in urine. On this basis, screening and confirmation tests for this equine urinary metabolite should be optimized for forensic control of remifentanil

Real-time imputation of missing predictor values in clinical practice

Use of prediction models is widely recommended by clinical guidelines, but usually requires complete information on all predictors that is not always available in daily practice. We describe two methods for real-time handling of missing predictor values when using prediction models in practice. We compare the widely used method of mean imputation (M-imp) to a method that personalizes the imputations by taking advantage of the observed patient characteristics. These characteristics may include both prediction model variables and other characteristics (auxiliary variables). The method was implemented using imputation from a joint multivariate normal model of the patient characteristics (joint modeling imputation; JMI). Data from two different cardiovascular cohorts with cardiovascular predictors and outcome were used to evaluate the real-time imputation methods. We quantified the prediction model's overall performance (mean squared error (MSE) of linear predictor), discrimination (c-index), calibration (intercept and slope) and net benefit (decision curve analysis). When compared with mean imputation, JMI substantially improved the MSE (0.10 vs. 0.13), c-index (0.70 vs 0.68) and calibration (calibration-in-the-large: 0.04 vs. 0.06; calibration slope: 1.01 vs. 0.92), especially when incorporating auxiliary variables. When the imputation method was based on an external cohort, calibration deteriorated, but discrimination remained similar. We recommend JMI with auxiliary variables for real-time imputation of missing values, and to update imputation models when implementing them in new settings or (sub)populations.Comment: 17 pages, 6 figures, to be published in European Heart Journal - Digital Health, accepted for MEMTAB 2020 conferenc

Word-List Intrusion Errors Predict Progression to Mild Cognitive Impairment

OBJECTIVE: Preclinical Alzheimer\u27s disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI. METHOD: Cognitively normal participants (n = 525) from the Alzheimer\u27s Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on the Rey Auditory Verbal Learning Test (AVLT; intrusion errors, learning slope, proactive interference, retroactive interference) predicted progression to MCI and a Clinical Dementia Rating (CDR) score of 1 after considering demographic characteristics, apolipoprotein E ε4 status, cerebrospinal fluid AD biomarkers, ischemia risk, mood, functional difficulty, and standard neuropsychological total test scores for the model. RESULTS: Baseline AVLT intrusion errors predicted progression to MCI (hazard ratio = 1.04, 95% confidence interval 1.01-1.07, p = .008) and improved model fit after the other valuable predictors were already in the model, χ2(df = 1) = 6.330, p = .012. AVLT intrusion errors also predicted progression to CDR = 1 (hazard ratio = 1.10, 95% confidence interval 1.02-1.18, p = .016) and again improved model fit, χ2(df = 1) = 4.682, p = .030. CONCLUSIONS: Intrusion errors on the AVLT contribute unique value for predicting progression from normal cognition to MCI and normal cognition to mild dementia (CDR = 1). Intrusion errors appear to reflect subtle change and inefficiencies in cognition that precede impairment detected by neuropsychological total scores

Interactions between U(1)U(1) Cosmic Strings: An Analytical Study

We derive analytic expressions for the interaction energy between two general $U(1)$ cosmic strings as the function of their relative orientation and the ratio of the coupling constants in the model. The results are relevant to the statistic description of strings away from critical coupling and shed some light on the mechanisms involved in string formation and the evolution of string networks.Comment: 31 pages,REVTEX, Imperial/TP/93-94/3