Bioequivalence of Oral Products and the Biopharmaceutics Classification System: Science, Regulation, and Public Policy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109935/1/cptclpt2011109.pd

What Should I Trust? Individual Differences in Attitudes to Conflicting Information and Misinformation on COVID-19

The COVID-19 pandemic constitutes a novel threat and traditional and new media provide people with an abundance of information and misinformation on the topic. In the current study, we investigated who tends to trust what type of mis/information. The data were collected in Norway from a sample of 405 participants during the first wave of COVID-19 in April 2020. We focused on three kinds of belief: the belief that the threat is overrated (COVID-threat skepticism), the belief that the threat is underrated (COVID-threat belief) and belief in misinformation about COVID-19. We studied sociodemographic factors associated with these beliefs and the interplay between attitudes to COVID-19, media consumption and prevention behavior. All three types of belief were associated with distrust in information about COVID-19 provided by traditional media and distrust in the authorities' approach to the pandemic. COVID-threat skepticism was associated with male gender, reduced news consumption since the start of the pandemic and lower levels of precautionary measures. Belief that the COVID-19 threat is underrated was associated with younger age, left-wing political orientation, increased news consumption during the pandemic and increased precautionary behavior. Consistent with the assumptions of the theory of planned behavior, individual beliefs about the seriousness of the COVID-19 threat predicted the extent to which individual participants adopted precautionary health measures. Both COVID-threat skepticism and COVID-threat belief were associated with endorsement of misinformation on COVID-19. Participants who endorsed misinformation tended to: have lower levels of education; be male; show decreased news consumption; have high Internet use and high trust in information provided by social media. Additionally, they tended to endorse multiple misinformation stories simultaneously, even when they were mutually contradictory. The strongest predictor for low compliance with precautionary measures was endorsement of a belief that the COVID-19 threat is overrated which at the time of the data collection was held also by some experts and featured in traditional media. The findings stress the importance of consistency of communication in situations of a public health threat

Numerical Simulations and the Strength of the Electroweak Phase Transition

Numerical simulations are performed to study the finite temperature phase transition in the SU(2) Higgs model on the lattice. The strength of the first order phase transition is investigated by determining the latent heat and the interface tension on $L_t=2$ lattices. The values of the Higgs boson mass presently chosen are below 50 GeV. Our results are in qualitative agreement with two-loop resummed perturbation theory.Comment: (Only a few minor changes compared to the original version.) 9 pages and 2 figures, DESY-94-08

Paired Associative Stimulation of the Auditory System: A Proof-Of-Principle Study

Background Paired associative stimulation (PAS) consisting of repeated application of transcranial magnetic stimulation (TMS) pulses and contingent exteroceptive stimuli has been shown to induce neuroplastic effects in the motor and somatosensory system. The objective was to investigate whether the auditory system can be modulated by PAS. Methods Acoustic stimuli (4 kHz) were paired with TMS of the auditory cortex with intervals of either 45 ms (PAS(45 ms)) or 10 ms (PAS(10 ms)). Two-hundred paired stimuli were applied at 0.1 Hz and effects were compared with low frequency repetitive TMS (rTMS) at 0.1 Hz (200 stimuli) and 1 Hz (1000 stimuli) in eleven healthy students. Auditory cortex excitability was measured before and after the interventions by long latency auditory evoked potentials (AEPs) for the tone (4 kHz) used in the pairing, and a control tone (1 kHz) in a within subjects design. Results Amplitudes of the N1-P2 complex were reduced for the 4 kHz tone after both PAS(45 ms) and PAS(10 ms), but not after the 0.1 Hz and 1 Hz rTMS protocols with more pronounced effects for PAS(45 ms). Similar, but less pronounced effects were observed for the 1 kHz control tone. Conclusion These findings indicate that paired associative stimulation may induce tonotopically specific and also tone unspecific human auditory cortex plasticity

The progression of chronic tinnitus over the years

Little is known about the trajectory of tinnitus over time. This study addressed (1) how often tinnitus remitted in patients with chronic tinnitus; (2) how subjective reported tinnitus characteristics, such as loudness, laterality, and type and measures of burden, such as tinnitus distress, depression, and quality of life, changes over time; (3) how often tinnitus-specific treatments were undertaken and the prevalence of comorbidities, (4) if the number of treatments and comorbidities were associated to changes in tinnitus distress over time. Data from 388 patients with chronic tinnitus who visited a tertiary tinnitus clinic between 2012 and 2017 were interrogated via a mail survey in 2018. Tinnitus characteristics were measured with the Tinnitus Sample Case History Questionnaire and numeric rating scales; tinnitus distress with Tinnitus Handicap Inventory (THI) and the Tinnitus Questionnaire (TQ), depression with the Major Depression Inventory and Quality of life with the World Health Organisation Quality of Life BREF at both time points and the clinical global impression scale. Comorbidities experienced and undertaken treatments were assessed with an in-house survey. Three participants (0.8% of the sample) reported tinnitus remission between both assessments. A decrease in the THI and TQ, and numeric ratings for tinnitus severity, annoyance, unpleasantness, and discomfort was observed, but no differences in tinnitus characteristics, depression, quality of life or overall health status. 64% presented at least one comorbidity, and 88% sought at least on tinnitus-specific treatment. Common comorbidities were psychological and sleeping problems, and the most common interventions were going to the dentist, taking medications, and wearing hearing aids. Our results suggest that full remission of tinnitus is a rare condition, that tinnitus distress on average decreases over time, and that tinnitus characteristics, quality of life, and depression tend to remain unaltered. The high number of interventions and comorbidities displayed minimal association to the changes in tinnitus distress, highlighting the substantial and durable burden of tinnitus sufferers

Efficacy and safety of bilateral continuous theta burst stimulation (cTBS) for the treatment of chronic tinnitus: design of a three-armed randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tinnitus, the perception of sound and noise in absence of an auditory stimulus, has been shown to be associated with maladaptive neuronal reorganization and increased activity of the temporoparietal cortex. Transient modulation of tinnitus by repetitive transcranial magnetic stimulation (rTMS) indicated that these areas are critically involved in the pathophysiology of tinnitus and suggested new treatment strategies. However, the therapeutic efficacy of rTMS in tinnitus is still unclear, individual response is variable, and the optimal stimulation area disputable. Recently, continuous theta burst stimulation (cTBS) has been put forward as an effective rTMS protocol for the reduction of pathologically enhanced cortical excitability.</p> <p>Methods</p> <p>48 patients with chronic subjective tinnitus will be included in this randomized, placebo controlled, three-arm trial. The treatment consists of two trains of cTBS applied bilaterally to the secondary auditory cortex, the temporoparietal associaction cortex, or to the lower occiput (sham condition) every working day for four weeks. Primary outcome measure is the change of tinnitus distress as quantified by the Tinnitus Questionnaire (TQ). Secondary outcome measures are tinnitus loudness and annoyance as well as tinnitus change during and after treatment. Audiologic and speech audiometric measurements will be performed to assess potential side effects. The aim of the present trail is to investigate effectiveness and safety of a four weeks cTBS treatment on chronic tinnitus and to compare two areas of stimulation. The results will contribute to clarify the therapeutic capacity of rTMS in tinnitus.</p> <p>Trial registration</p> <p>The trial was registered with the clinical trials register of <url>http://www.clinicaltrials.gov</url> (NCT00518024).</p

Temperature forecasting by deep learning methods

Numerical weather prediction (NWP) models solve a system of partial differential equations based on physical laws to forecast the future state of the atmosphere. These models are deployed operationally, but they are computationally very expensive. Recently, the potential of deep neural networks to generate bespoke weather forecasts has been explored in a couple of scientific studies inspired by the success of video frame prediction models in computer vision. In this study, a simple recurrent neural network with convolutional filters, called ConvLSTM, and an advanced generative network, the Stochastic Adversarial Video Prediction (SAVP) model, are applied to create hourly forecasts of the 2 m temperature for the next 12 h over Europe. We make use of 13 years of data from the ERA5 reanalysis, of which 11 years are utilized for training and 1 year each is used for validating and testing. We choose the 2 m temperature, total cloud cover, and the 850 hPa temperature as predictors and show that both models attain predictive skill by outperforming persistence forecasts. SAVP is superior to ConvLSTM in terms of several evaluation metrics, confirming previous results from computer vision that larger, more complex networks are better suited to learn complex features and to generate better predictions. The 12 h forecasts of SAVP attain a mean squared error (MSE) of about 2.3 K2, an anomaly correlation coefficient (ACC) larger than 0.85, a structural similarity index (SSIM) of around 0.72, and a gradient ratio (rG) of about 0.82. The ConvLSTM yields a higher MSE (3.6 K2), a smaller ACC (0.80) and SSIM (0.65), and a slightly larger rG (0.84). The superior performance of SAVP in terms of MSE, ACC, and SSIM can be largely attributed to the generator. A sensitivity study shows that a larger weight of the generative adversarial network (GAN) component in the SAVP loss leads to even better preservation of spatial variability at the cost of a somewhat increased MSE (2.5 K2). Including the 850 hPa temperature as an additional predictor enhances the forecast quality, and the model also benefits from a larger spatial domain. By contrast, adding the total cloud cover as predictor or reducing the amount of training data to 8 years has only small effects. Although the temperature forecasts obtained in this way are still less powerful than contemporary NWP models, this study demonstrates that sophisticated deep neural networks may achieve considerable forecast quality beyond the nowcasting range in a purely data-driven way.</p

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. Registered on 12 March 2015 revised on 15 March 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1399-9) contains supplementary material, which is available to authorized users

A microscopic semiclassical confining field equation for U(1)U(1) lattice gauge theory in 2+1 dimensions

We present a semiclassical nonlinear field equation for the confining field in 2+1--dimensional $U(1)$ lattice gauge theory (compact QED). The equation is derived directly from the underlying microscopic quantum Hamiltonian by means of truncation. Its nonlinearities express the dynamic creation of magnetic monopole currents leading to the confinement of the electric field between two static electric charges. We solve the equation numerically and show that it can be interpreted as a London relation in a dual superconductor.Comment: 21 pages, epsf postscript figures included, full postscript available at ftp://ftp.th.physik.uni-frankfurt.de/pub/cbest/micro.ps.Z or http://www.th.physik.uni-frankfurt.de/~cbest/pub.htm