Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

Context: Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release.

Objective: To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets.

Materials and methods: IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet.

Results: IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol.

Discussion: IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets.

Conclusion: IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.     

Microstructure and Processing of 3D Printed Tungsten Microlattices and Infiltrated W–Cu Composites

Tungsten is of industrial relevance due its outstanding intrinsic properties (e.g., highest melting‐point of all elements) and therefore difficult to 3D‐print by conventional methods. Here, tungsten micro‐lattices are produced by room‐temperature extrusion‐based 3D‐printing of an ink comprising WO₃–0.5%NiO submicron powders, followed by H₂‐reduction and Ni‐activated sintering. The green bodies underwent isotropic linear shrinkage of ≈50% during the thermal treatment resulting in micro‐lattices, with overall 35–60% open‐porosity, consisting of 95–100% dense W–0.5%Ni struts having ≈80–300 μm diameter. Ball‐milling the powders and inks reduced the sintering temperature needed to achieve full densification from 1400 to 1200 °C and enabled the ink to be extruded through finer nozzles (200 μm). Partial sintering of the struts is achieved when NiO is omitted from the ink, with submicron interconnected‐porosity of ≈34%. Several tungsten micro‐lattices are infiltrated with molten copper at 1300 °C under vacuum, resulting in dense, anisotropic W–Cu composites with 40–65% tungsten volume fraction. Partially sintered struts (containing nickel) with submicron open porosity are also infiltrated with Cu, resulting in co‐continuous W–Cu composites with wide W struts/Cu channels at the lattice scale (hundreds of micrometers), and fine W–Cu interpenetrating network at the strut scale (hundreds of nanometers) allowing for the design of anisotropic mechanical and electrical properties.

     

Focus groups reveal perils and promises of managed care for nurse practitioners

Decades of practice and research suggest that nurse practitioners (NPs) provide cost-effective and high-quality care. Managed care's emphasis on prevention and cost savings led some policy makers to view NPs as a way to meet the need for primary care providers. However, access to and utilization of NPs has increasingly been controlled by managed care organizations (MCOs) through their selection of providers for primary care panels. This study employed qualitative methodology to examine NPs' experiences with MCOs. Three focus groups, comprising 27 NPs in New York and Connecticut, revealed NPs' mixed reactions to managed care and a range of sentiments regarding NPs' efforts to be listed as primary care providers. The results reflected NPs' concerns about their perceived "invisibility," as well as their sense of "invincibility" in the ways in which NPs are responding to the barriers posed by MCOs. They identified barriers to, as well as ways to facilitate, being listed by MCOs, and described the importance of NPs working individually and collectively in negotiating with MCOs.     

Staphylococcal enterotoxin B primes cytokine secretion and lytic activity in response to native bacterial antigens

Superantigens stimulate T-lymphocyte proliferation and cytokine production, but the effects of superantigen exposure on cell function within a complex, highly regulated immune response remain to be determined. In this study, we demonstrate that superantigen exposure significantly alters the murine host response to bacterial antigens in an in vitro coculture system. Two days after exposure to the superantigen staphylococcal enterotoxin B, splenocytes cultured with Streptococcus mutans produced significantly greater amounts of gamma interferon (IFN-gamma) and interleukin-12 than did sham-injected controls. The majority of IFN-gamma production appeared to be CD8(+) T-cell derived since depletion of this cell type dramatically reduced the levels of IFN-gamma. To study host cell damage that may occur following superantigen exposure, we analyzed cytotoxicity to "bystander" fibroblast cells cultured with splenocytes in the presence of bacterial antigens. Prior host exposure to staphylococcal enterotoxin B significantly enhanced fibroblast cytotoxicity in the presence of bacteria. Neutralization of IFN-gamma decreased the amount of cytotoxicity observed. However, a greater reduction was evident when splenocyte-bacterium cocultures were separated from the bystander cell monolayer via a permeable membrane support. Increased cytotoxicity appears to be primarily dependent upon cell-cell contact. Collectively, these data indicate that overproduction of inflammatory cytokines may alter the activity of cytotoxic immune cells. Superantigen exposure exacerbates cytokine production and lytic cell activity when immune cells encounter bacteria in vitro and comparable activities could possibly occur in vivo.     

Analysis of Gasolines by FT-IR Spectroscopy

An experimental and computational protocol was established for the simultaneous determination of several key gasoline properties from a single Fourier transform infrared (FT-IR) spectrum. The study has shown that midband FT-IR spectroscopy combined with multivariate calibration analysis is a versatile, efficient, and accurate technique for the simultaneous estimation of key gasoline properties within about 1 min with less than 2 mL of sample. The FT-IR-derived values of gasoline properties include research and motor octane numbers, aromatic, olefinic, and saturated hydrocarbon content, benzene content, and concentrations of ethanol, methyl tert-butyl ether, and total oxygen. Concentrations of other oxygenated compounds are expected to be equally predictable. However, since these oxygen-containing species have not been adequately represented among the currently commercially available gasoline samples, their calibration may only be achieved using laboratory fuel blends. Midrange boiling point data may also be estimated. Fuel properties determined by minor concentrations of fuel components, e.g., flash point, sulfur content, etc., may not be modeled because the corresponding FT-IR signals are below detection limits of presented experimental protocol. The precision of this procedure was shown to be comparable to reproducibility of the standard laboratory analyses used for direct measurement of specific fuel properties, with squared correlation coefficient (R(2)) ranging from 0.94 to 0.99 between the two sets of measurements. This new methodology could increase the corresponding output of the petroleum laboratories by a factor of over 200 to 1 while maintaining data integrity and minimizing sample requirements, environmental hazards, and cost.     

Development of a framework for truss-braced wing conceptual MDO

The paper describes the development of a multidisciplinary design optimization framework for conceptual design of truss-braced wing configurations. This unconventional configuration requires specialized analysis tools supported by a modular and flexible framework to accommodate different configurations. While the previous framework developed at Virginia Tech was a monolithic Fortran-77 code, the need for more flexibility for complex truss-braced wing configurations was addressed by the development of this new framework, which is based on Phoenix Integration ModelCenter^TM environment. The framework uses updated structural and aerodynamic design modules that enable a more general geometry definition. The new framework, thus, provides a foundation for future design concepts, especially multi-member truss-braced wing configurations. The fuel saving potential of these truss-braced wing configurations is presented by comparing different truss designs with gradually increased level of complexity.     

A survey of problems,solution techniques,and future challenges in scheduling semiconductor manufacturing operations

In this paper, we discuss scheduling problems in semiconductor manufacturing. Starting from describing the manufacturing process, we identify typical scheduling problems found in semiconductor manufacturing systems. We describe batch scheduling problems, parallel machine scheduling problems, job shop scheduling problems, scheduling problems with auxiliary resources, multiple orders per job scheduling problems, and scheduling problems related to cluster tools. We also present important solution techniques that are used to solve these scheduling problems by means of specific examples, and report on known implementations. Finally, we summarize some of the challenges in scheduling semiconductor manufacturing operations.     

SoundRiver: Semantically‐Rich Sound Illustration

Sound is an integral part of most movies and videos. In many situations, viewers of a video are unable to hear the sound track, for example, when watching it in a fast forward mode, viewing it by hearing‐impaired viewers or when the plot is given as a storyboard. In this paper, we present an automated visualization solution to such problems. The system first detects the common components (such as music, speech, rain, explosions, and so on) from a sound track, then maps them to a collection of programmable visual metaphors, and generates a composite visualization. This form of sound visualization, which is referred to as SoundRiver, can be also used to augment various forms of video abstraction and annotated key frames and to enhance graphical user interfaces for video handling software. The SoundRiver conveys more semantic information to the viewer than traditional graphical representations of sound illustration, such as phonoautographs, spectrograms or artistic audiovisual animations.