Biowaiver Monographs for Immediate‐Release Solid Oral Dosage Forms: Codeine Phosphate

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106898/1/jps23977.pd

Matching conditions and Higgs mass upper bounds revisited

Matching conditions relate couplings to particle masses. We discuss the importance of one-loop matching conditions in Higgs and top-quark sector as well as the choice of the matching scale. We argue for matching scales $\mu_{0,t} \simeq m_t$ and $\mu_{0,H} \simeq max[ m_t, M_H ]$. Using these results, the two-loop Higgs mass upper bounds are reanalyzed. Previous results for $\Lambda\approx$ few TeV are found to be too stringent. For $\Lambda=10^{19}$ GeV we find $M_H < 180 \pm 4\pm 5$ GeV, the first error indicating the theoretical uncertainty, the second error reflecting the experimental uncertainty due to $m_t=175\pm6$ GeV.Comment: 20 pages, 6 figures; uses epsf and rotate macro

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

Accessing directly the properties of fundamental scalars in the confinement and Higgs phase

The properties of elementary particles are encoded in their respective propagators and interaction vertices. For a SU(2) gauge theory coupled to a doublet of fundamental complex scalars these propagators are determined in both the Higgs phase and the confinement phase and compared to the Yang-Mills case, using lattice gauge theory. Since the propagators are gauge-dependent, this is done in the Landau limit of 't Hooft gauge, permitting to also determine the ghost propagator. It is found that neither the gauge boson nor the scalar differ qualitatively in the different cases. In particular, the gauge boson acquires a screening mass, and the scalar's screening mass is larger than the renormalized mass. Only the ghost propagator shows a significant change. Furthermore, indications are found that the consequences of the residual non-perturbative gauge freedom due to Gribov copies could be different in the confinement and the Higgs phase.Comment: 11 pages, 6 figures, 1 table; v2: one minor error corrected; v3: one appendix on systematic uncertainties added and some minor changes, version to appear in EPJ

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

Heavy-Higgs Lifetime at Two Loops

The Standard-Model Higgs boson with mass $M_H >> 2M_Z$ decays almost exclusively to pairs of $W$ and $Z$ bosons. We calculate the dominant two-loop corrections of $O( G_F^2 M_H^4 )$ to the partial widths of these decays. In the on-mass-shell renormalization scheme, the correction factor is found to be $1 + 14.6$, where the second term is the one-loop correction. We give full analytic results for all divergent two-loop Feynman diagrams. A subset of finite two-loop vertex diagrams is computed to high precision using numerical techniques. We find agreement with a previous numerical analysis. The above correction factor is also in line with a recent lattice calculation.Comment: 26 pages, 6 postscript figures. The complete paper including figures is also available via WWW at http://www.physik.tu-muenchen.de/tumphy/d/T30d/PAPERS/TUM-HEP-247-96.ps.g

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

The demonstration of bioequivalence (BE) is an essential requirement for ensuring that patients receive a product that performs as indicated by the label. The BE standard for a particular product is set by its innovator, and this standard must subsequently be matched by generic drug products. The Biopharmaceutics Classification System (BCS) sets a scientific basis for an improved BE standard for immediate-release solid oral dosage forms. In this paper, we discuss BE and the BCS, as well as the issues that are currently relevant to BE as a pharmaceutical product standard

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

Quality by design (QbD) approach for a nanoparticulate imiquimod formulation as an investigational medicinal product

The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment of actinic keratosis (AK) against the comparator Aldara (EudraCT: 2015-002203-28). The design of the QbD elements of a quality target product profile (QTPP) enables the identification of the critical quality attributes (CQAs) of the drug product as the content of IMQ, the particle-size distribution, the pH, the rheological properties, the permeation rate and the chemical, physical and microbiological stability. Critical material attributes (CMAs) and critical process parameters (CPPs) are identified by using a risk-based approach in an Ishikawa diagram and in a risk-estimation matrix. In this study, the identified CPPs of the wet media ball-milling process’s milling time and milling speed are evaluated in a central composite design of experiments (DoEs) approach, revealing criticality for both factors for the resulting mean particle size, while only the milling time is significantly affecting the polydispersity. To achieve a mean particle size in the range of 300–400 nm with a minimal PdI, the optimal process conditions are found to be 650 rpm for 135 min. Validating the model reveals a good correlation between the predicted and observed values. Adequate control strategies were implemented for intermediate products as in-process controls (IPCs) and quality control (QC) tests of the identified CQAs. The IPC and QC data from 13 “IMI-Gel” batches manufactured in adherence to good manufacturing practice (GMP) reveal consistent quality with minimal batch-to-batch variability