Criminal Liability Under the Food, Drug, and Cosmetic Act

The criminal provisions of the Federal Food, Drug, and Cosmetic Act (FDCA)' and the judicial interpretation thereof afford the Food and Drug Administration (FDA) great discretion, in determining both when and against whom criminal prosecution is warranted. Though it may employ a wide variety of enforcement mechanisms, the FDA has relied in recent years ever more heavily on criminal proceedings. Absent appropriate guidelines, however, extensive use of criminal sanctions to enforce the FDCA potentially leads to costly, inefficient, and unnecessary prosecutions. This paper attempts to define such guidelines in the context of criminal liability for corporate officers and employees. First, the paper will describe corporate liability under the FDCA. Next, it will utilize economic tools to propose guidelines to help determine when this liability is best imposed. Finally, it will examine the factual settings of two seminal cases in food and drug law using the proposed guidelines

Improving Credibility by Delegating Judicial Competence: The Case of the Judicial Committee of the Privy Council

It is argued that government credibility is an important resource and that it can be improved by delegating decision-making competence beyond the nation-state. It is hypothesized that such delegation should result in higher income and growth. Some former British colonies retained the Judicial Committee of the Privy Council as their final court of appeals even after independence. This court is thus taken as a natural experiment to test our hypothesis. It turns out that retaining the jurisdiction is indeed significant for explaining economic growth

Automatic grid construction for few-body quantum mechanical calculations

An algorithm for generating optimal nonuniform grids for solving the two-body Schr\"odinger equation is developed and implemented. The shape of the grid is optimized to accurately reproduce the low-energy part of the spectrum of the Schr\"odinger operator. Grids constructed this way are applicable to more complex few-body systems where the number of grid points is a critical limitation to numerical accuracy. The utility of the grid generation for improving few-body calculations is illustrated through an application to bound states of He trimers

Two- versus three-dimensional dual gradient-echo MRI of the liver: a technical comparison

Objective: To compare 2D spoiled dual gradient-echo (SPGR-DE) and 3D SPGR-DE with fat and water separation for the assessment of focal and diffuse fatty infiltration of the liver. Methods: A total of 227 consecutive patients (141 men; 56 ± 14years) underwent clinically indicated liver MRI at 1.5T including multiple-breath-hold 2D SPGR-DE and single-breath-hold 3D SPGR-DE with automatic reconstruction of fat-only images. Two readers assessed the image quality and number of fat-containing liver lesions on 2D and 3D in- and opposed-phase (IP/OP) images. Liver fat content (LFC) was quantified in 138 patients without chronic liver disease from 2D, 3D IP/OP, and 3D fat-only images. Results: Mean durations of 3D and 2D SPGR-DE acquisitions were 23.7 ± 2.9 and 97.2 ± 9.1s respectively. The quality of all 2D and 3D images was rated diagnostically. Three-dimensional SPGR-DE revealed significantly more breathing artefacts resulting in lower image quality (P < 0.001); 2D and 3D IP/OP showed a similar detection rate of fat-containing lesions (P = 0.334) and similar LFC estimations (mean: +0.4%; P = 0.048). LFC estimations based on 3D fat-only images showed significantly higher values (mean: 2.7% + 3.5%) than those from 2D and 3D IP/OP images (P < 0.001). Conclusion: Three dimensional SPGR-DE performs as well as 2D SPGR-DE for the assessment of focal and diffuse fatty infiltration of liver parenchyma. The 3D SPGR-DE sequence used was quicker but more susceptible to breathing artefacts. Significantly higher LFC values are derived from 3D fat-only images than from 2D or 3D IP/OP images. Key Points: • Magnetic resonance imaging can assess focal and diffuse hepatic fatty infiltration • Both 2D and 3D dual-echo MRI techniques can be used for chemical shift imaging of the liver. • The single breath-hold 3D dual-echo technique is faster but more susceptible to breathing artefacts. • Three-dimensional fat-only images show higher fat estimates than in- and out-of-phase image

Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels

Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions

Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne.

BACKGROUND: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied. OBJECTIVES: Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne. METHODS: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator\u27s Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results. RESULTS: In both studies, at week 12 the facial success rates according to the Investigator\u27s Global Assessment and truncal Physician\u27s Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P \u3c .001) in favor of trifarotene when compared with the vehicle. LIMITATIONS: Adjunctive topical or systemic treatments were not studied. CONCLUSION: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne

A Case Report

The objective of this case report is to introduce a customized CAD/CAM freeze- dried bone allograft (FDBA) block for its use in Guided Bone Regeneration (GBR) procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show optimal integration behavior of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept. View Full-Tex

Evidence for an exotic S=-2, Q=-2 baryon resonance in proton-proton collisions at the CERN SPS

Results of resonance searches in the Xi - pi -, Xi - pi +, Xi -bar+ pi -, and Xi -bar+ pi + invariant mass spectra in proton-proton collisions at sqrt[s]=17.2 GeV are presented. Evidence is shown for the existence of a narrow Xi - pi - baryon resonance with mass of 1.862±0.002 GeV/c2 and width below the detector resolution of about 0.018 GeV/c2. The significance is estimated to be above 4.2 sigma . This state is a candidate for the hypothetical exotic Xi --3/2 baryon with S=-2, I=3 / 2, and a quark content of (dsdsu-bar). At the same mass, a peak is observed in the Xi - pi + spectrum which is a candidate for the Xi 03/2 member of this isospin quartet with a quark content of (dsusd-bar). The corresponding antibaryon spectra also show enhancements at the same invariant mass

Magnetization transfer for the assessment of bowel fibrosis in patients with Crohn's disease: initial experience

Object: To assess the feasibility of magnetization transfer (MT) imaging of the bowel wall in patients with Crohn's disease (CD), and to evaluate its utility for the detection of intestinal fibrosis. Materials and methods: In this prospective study, 31 patients (age 39.0±13.2years) with CD were examined in a 1.5T MR scanner. To establish a standard of reference, two independent readers classified the patients in different disease states using standard MR enterography, available clinical data and histological findings. In addition to the standard protocol, a 2D gradient-echo sequence (TR/TE 32ms/2.17ms; flip angle 25°) with/without 1,100Hz off-resonance prepulse was applied. MT ratios (MTR) of the small bowel wall were computed off-line on a pixel-by-pixel basis. Results: The MT sequences acquired images of sufficient quality and spatial resolution for the evaluation of the small bowel wall without detrimental motion artefacts. In normal bowel wall segments, an intermediate MTR of 25.4±3.4% was measured. The MTR was significantly increased in bowel wall segments with fibrotic scarring (35.3±4.0%, p<0.0001). In segments with acute inflammation, the mean MTR was slightly smaller (22.9±2.2%). Conclusion: MT imaging of the small bowel wall is feasible in humans with sufficient image quality and may help with the identification of fibrotic scarring in patients with C