Reforming Punishment of Financial Reporting Fraud

Present sentencing law in criminal cases of financial reporting fraud is embarrassingly flawed. The problem is urgent given that courts are now regularly sentencing corporate offenders, sometimes (but sometimes not) to extremely punitive terms of imprisonment. Policing of fraud by multiple jurisdictions in a federal system means that principled sentencing law is necessary not only for first-order policy reasons but also for coordination of sanctioning efforts. Proportionality and rationality demand that sentencing law have an agreed scale for measuring cases of financial reporting fraud in relation to each other, a sound methodology for fixing a given case on that scale, and a reasoned calibration of that scale. Current federal law, which controls most such cases and is a focal point for non-federal cases and public debate, is close to sensible on the first score but far off the mark on the other two. In this contribution to a symposium on Fraud and Federalism, I describe problems in present law and offer relatively uncontroversial reform measures that could substantially improve the law governing sentencing of financial reporting fraud

Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial

Geopolymer/PEG Hybrid Materials Synthesis and Investigation of the Polymer Influence on Microstructure and Mechanical Behavior

Geopolymers are aluminosilicate inorganic polymers, obtained from the alkali activation of powders containing SiO2+Al2O3>80wt%, mainly proposed as environmentally friendly building materials. In this work, metakaolin-based geopolymers have been prepared and a water-soluble polymer, polyethylene glycol (PEG), has been added in different percentages to obtain organic-inorganic hybrid geopolymers. The influence of both the polymer amount and aging time on the structure and the mechanical behavior of the materials were investigated. FTIR spectroscopy allowed us to follow the evolution of the aluminosilicate framework during the geopolymerization process. This analysis revealed that PEG leads to a network which is rich in Al-O-Si bonds and forms H-bonds with the inorganic phase. SEM microscope showed that the two phases are interpenetrated on micrometric scales. Traction and bending tests have been carried out on appropriate samples to investigate the mechanical behavior of the obtained hybrids, showing that both PEG content and aging time affect the material behavior

Diffusion Controlled Drug Release from Slurry Formed, Porous, Organic and Clay-derived Pellets

Coronary artery disease and chronic pain are serious health issues that cause severe discomfort and suffering in society today. Antithrombotic agents and highly potent analgesics play a critical role in improving the recovery process for patients being treated for these diseases. This thesis focuses on the design and study of pellet-based drug dosage forms which allow diffusion-controlled delivery of drugs with the aim of achieving optimal therapeutic outcomes. A wet slurry process was used to mix the drug and the polymer and/or clay precursor excipients into a paste. The pellets were then shaped via ionotropic gelation (alginate hydrogel beads/pellets), extrusion/spheronization (halloysite clay pellets) or geopolymerization. The decrease in the drug diffusion rate in the alginate beads was affected by the drug's molecular size and charge and the characteristics (such as concentration and chemical structure) of the surrounding alginate gel. The halloysite clay pellets provided sustained release of the highly potent drug fentanyl at both gastric pH 1 and intestinal pH 6.8. As expected, crushing the pellets reduced the diffusion barrier, resulting in more rapid release (dose dumping). The use of mechanically strong geopolymer gels was investigated as a potential means of preventing dose dumping as a result of crushing of the dosage form. Variations in the synthesis composition resulted in drastic changes in the microstructure morphology, the porosity, the mechanical stability and the drug release rate. Pore network modeling and finite element simulations were employed to theoretically evaluate the effects of porosity and drug solubility in the geopolymer structure on the drug release process. Fitting the model parameters to experimental data showed that increased average pore connectivity, a greater pore size distribution, and increased drug solubility in the pellet resulted in an increased drug release rate. Furthermore, incorporation of pH-sensitive organic polymers in the geopolymer structure reduced the high drug release rate from the pellets at gastric pH. These results indicate that geopolymers have potential for use in pellet form; both the release rate of the drug and the mechanical stability of the pellets can be optimized to prevent dose dumping

Diffusion Controlled Drug Release from Slurry Formed, Porous, Organic and Clay-derived Pellets

Coronary artery disease and chronic pain are serious health issues that cause severe discomfort and suffering in society today. Antithrombotic agents and highly potent analgesics play a critical role in improving the recovery process for patients being treated for these diseases. This thesis focuses on the design and study of pellet-based drug dosage forms which allow diffusion-controlled delivery of drugs with the aim of achieving optimal therapeutic outcomes. A wet slurry process was used to mix the drug and the polymer and/or clay precursor excipients into a paste. The pellets were then shaped via ionotropic gelation (alginate hydrogel beads/pellets), extrusion/spheronization (halloysite clay pellets) or geopolymerization. The decrease in the drug diffusion rate in the alginate beads was affected by the drug's molecular size and charge and the characteristics (such as concentration and chemical structure) of the surrounding alginate gel. The halloysite clay pellets provided sustained release of the highly potent drug fentanyl at both gastric pH 1 and intestinal pH 6.8. As expected, crushing the pellets reduced the diffusion barrier, resulting in more rapid release (dose dumping). The use of mechanically strong geopolymer gels was investigated as a potential means of preventing dose dumping as a result of crushing of the dosage form. Variations in the synthesis composition resulted in drastic changes in the microstructure morphology, the porosity, the mechanical stability and the drug release rate. Pore network modeling and finite element simulations were employed to theoretically evaluate the effects of porosity and drug solubility in the geopolymer structure on the drug release process. Fitting the model parameters to experimental data showed that increased average pore connectivity, a greater pore size distribution, and increased drug solubility in the pellet resulted in an increased drug release rate. Furthermore, incorporation of pH-sensitive organic polymers in the geopolymer structure reduced the high drug release rate from the pellets at gastric pH. These results indicate that geopolymers have potential for use in pellet form; both the release rate of the drug and the mechanical stability of the pellets can be optimized to prevent dose dumping

Diffusion Controlled Drug Release from Slurry Formed, Porous, Organic and Clay-derived Pellets

Coronary artery disease and chronic pain are serious health issues that cause severe discomfort and suffering in society today. Antithrombotic agents and highly potent analgesics play a critical role in improving the recovery process for patients being treated for these diseases. This thesis focuses on the design and study of pellet-based drug dosage forms which allow diffusion-controlled delivery of drugs with the aim of achieving optimal therapeutic outcomes. A wet slurry process was used to mix the drug and the polymer and/or clay precursor excipients into a paste. The pellets were then shaped via ionotropic gelation (alginate hydrogel beads/pellets), extrusion/spheronization (halloysite clay pellets) or geopolymerization. The decrease in the drug diffusion rate in the alginate beads was affected by the drug's molecular size and charge and the characteristics (such as concentration and chemical structure) of the surrounding alginate gel. The halloysite clay pellets provided sustained release of the highly potent drug fentanyl at both gastric pH 1 and intestinal pH 6.8. As expected, crushing the pellets reduced the diffusion barrier, resulting in more rapid release (dose dumping). The use of mechanically strong geopolymer gels was investigated as a potential means of preventing dose dumping as a result of crushing of the dosage form. Variations in the synthesis composition resulted in drastic changes in the microstructure morphology, the porosity, the mechanical stability and the drug release rate. Pore network modeling and finite element simulations were employed to theoretically evaluate the effects of porosity and drug solubility in the geopolymer structure on the drug release process. Fitting the model parameters to experimental data showed that increased average pore connectivity, a greater pore size distribution, and increased drug solubility in the pellet resulted in an increased drug release rate. Furthermore, incorporation of pH-sensitive organic polymers in the geopolymer structure reduced the high drug release rate from the pellets at gastric pH. These results indicate that geopolymers have potential for use in pellet form; both the release rate of the drug and the mechanical stability of the pellets can be optimized to prevent dose dumping

Modeling structure-function relationships for diffusive drug transport in inert porous geopolymer matrices

A unique structure-function relationship investigation of mechanically strong geopolymer drug delivery vehicles for sustained release of potent substances is presented. The effect of in-synthesis water content on geopolymer pore structure and diffusive drug transport is investigated. Scanning electron microscopy, N(2) gas adsorption, mercury intrusion porosimetry, compression strength test, drug permeation, and release experiments are performed. Effective diffusion coefficients are measured and compared with corresponding theoretical values as derived from pore size distribution and connectivity via pore-network modeling. By solely varying the in-synthesis water content, mesoporous and mechanically strong geopolymers with porosities of 8%-45% are obtained. Effective diffusion coefficients of the model drugs Saccharin and Zolpidem are observed to span two orders of magnitude (∼1.6-120 × 10(-8) cm(2) /s), comparing very well to theoretical estimations. The ability to predict drug permeation and release from geopolymers, and materials alike, allows future formulations to be tailored on a structural and chemical level for specific applications such as controlled drug delivery of highly potent substances

In situ and Operando Raman Spectroscopy of Layered Transition Metal Oxides for Li-ion Battery Cathodes

In situ and operando Raman spectroscopy is proposed to provide unique means for deeper fundamental understanding and further development of layered transition metal LiMO2 (M = Ni, Co, Mn) oxides suitable for Li-ion battery applications. We compare several spectro-electrochemical cell designs and suggest key experimental parameters for obtaining optimum electrochemical performance and spectral quality. Studies of the most practically relevant LiMO2 compositions are exemplified with particular focus on two experimental approaches: (1) lateral and axial Raman mapping of the electrode's (near-) surface to monitor inhomogeneous electrode reactions and (2) time-dependent single-particle spectra during cycling to analyze the LixMO2 lattice dynamics as a function of lithium content. Raman Spectroscopy is claimed to provide a unique real-time probe of the M-O bonds, which are at the heart of the electrochemistry of LiMO2 oxides and govern their stability. We highlight the need for further fundamental understanding of the relationships between the spectroscopic response and oxide lattice structure with particular emphasis on the development of a theoretical framework linking the position and intensity of the Raman bands to the local LixMO2 lattice con figuration. The use of complementary experimental techniques and model systems for validation also deserve further attention. Several novel LiMO2 compositions are currently being explored, especially containing dopings and coatings, and Raman spectroscopy could offer a highly dynamic and convenient tool to guide the formulation of high specific charge and long cycle life LiMO2 oxides for next-generation Li-ion battery cathodes

Isoindole-4,7-diones as Candidates for Organic Lithium Ion Battery Polymer Cathodes

<p>Poster</p