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There has been a recent proposal by Gergel and Owen for introduction of legally enforceable self-binding directives for persons with bipolar affective disorder in the United Kingdom. The model is rooted in presence or absence of decision-making capacity, and the notion of capacity used is an expansion of the usual notion of capacity, in that it is individualized and diachronic. In this article, I argue that an individualized notion of capacity either lacks a coherent foundation or exposes itself to a situation where epistemological error results in a double standard or unjustified enforcement of the directive. I also raise concern that the diachronic notion of capacity leads to an authenticity type account, which fails to incorporate differences in individual prognosis. I then present a rough sketch of an alternative account, more in keeping with current mental health legislation, which uses an individualized notion of "risk to self" to justify self-binding directives in bipolar disorder.

Many layered crystal phases can be exfoliated or assembled into ultrathin two-dimensional (2D) nanosheets with novel properties not achievable by particulate or fibrous nanoforms. Among these 2D materials are manganese dioxide (MnO2) nanosheets, which have applications in batteries, catalysts, and biomedical probes. A novel feature of MnO2 is its sensitivity to chemical reduction leading to dissolution and Mn2+ release. Biodissolution is critical for nanosafety assessment of 2D materials, but the timing and location of MnO2 biodissolution in environmental or occupational exposure scenarios are poorly understood. This work investigates the chemical and colloidal dynamics of MnO2 nanosheets in biological media for environmental and human health risk assessment. MnO2 nanosheets are insoluble in most aqueous phases, but react with strong and weak reducing agents in biological fluid environments. In vitro, reductive dissolution can be slow enough in cell culture media for MnO2 internalization by cells in the form of intact nanosheets, which localize in vacuoles, react to deplete intracellular glutathione, and induce cytotoxicity that is likely mediated by intracellular Mn2+ release. The results are used to classify MnO2 nanosheets within a new hazard screening framework for 2D materials, and the implications of MnO2 transformations for nanotoxicity testing and nanosafety assessment are discussed.

Marriage is a social tie associated with health advantages for adults and their children, as lower rates of preterm birth and low birth weight are observed among married women. This study tests two competing hypotheses explaining these marriage advantages-marriage protection versus marriage selection-using a sample of recent births to single, cohabiting, and married women from the National Survey of Family Growth, 2006-10. Propensity score matching and fixed effects regression results demonstrate support for marriage selection, as a rich set of early life selection factors account for all of the cohabiting-married disparity and part of the single-married disparity. Subsequent analyses demonstrate prenatal smoking mediates the adjusted single-married disparity in birth weight, lending some support for the marriage protection perspective. Study findings sharpen our understanding of why and how marriage matters for child well-being, and provide insight into preconception and prenatal factors describing intergenerational transmissions of inequality via birth weight.

Two models seeking to explain the growth and decline of religious groups are prevalent in the literature. The religious market approach emphasizes the role of intergroup competition and in doing so focuses on religious switching. Another perspective emphasizes demographic mechanisms, particularly fertility. Research to date has not considered how switching and fertility interact as mechanisms of growth. Switching and fertility share a significant role in the growth trajectory of a religious group. Early success in gaining members through switching has an important long-term impact which fertility alone cannot produce. The age of those switching into a group can also have significant consequences for the effects of fertility.

We examined seven life-course pathways from adolescence through the early adult years and their links with general health and psychosocial adjustment among 2,290 women from the National Longitudinal Study of Adolescent Health. Young women who followed a pathway involving college attendance to full-time employment with no family-formation transitions were functioning comparatively well with respect to general health, depression, and self-esteem. In contrast, young women who followed pathways involving early motherhood were functioning less well. Fixed-effects models suggested that the differences were due to selection factors. Young women who followed the pathway of college to full-time employment exhibited an increase in heavy drinking, whereas women who became married mothers exhibited a decrease in the same. Involvement in illegal behavior declined for all groups but least so for women who attended college.

Human diseases associated with exposure to asbestos fibers include pleural fibrosis and plaques, pulmonary fibrosis (asbestosis), lung cancer, and diffuse malignant mesothelioma. The critical determinants of fiber bioactivity and toxicity include not only fiber dimensions, but also shape, surface reactivity, crystallinity, chemical composition, and presence of transition metals. Depending on their size and dimensions, inhaled fibers can penetrate the respiratory tract to the distal airways and into the alveolar spaces. Fibers can be cleared by several mechanisms, including the mucociliary escalator, engulfment, and removal by macrophages, or through splitting and chemical modification. Biopersistence of long asbestos fibers can lead to inflammation, granuloma formation, fibrosis, and cancer. Exposure to synthetic carbon nanomaterials, including carbon nanofibers and carbon nanotubes (CNTs), is considered a potential health hazard because of their physical similarities with asbestos fibers. Respiratory exposure to CNTs can produce an inflammatory response, diffuse interstitial fibrosis, and formation of fibrotic granulomas similar to that observed in asbestos-exposed animals and humans. Given the known cytotoxic and carcinogenic properties of asbestos fibers, toxicity of fibrous nanomaterials is a topic of intense study. The mechanisms of nanomaterial toxicity remain to be fully elucidated, but recent evidence suggests points of similarity with asbestos fibers, including a role for generation of reactive oxygen species, oxidative stress, and genotoxicity. Considering the rapid increase in production and use of fibrous nanomaterials, it is imperative to gain a thorough understanding of their biologic activity to avoid the human health catastrophe that has resulted from widespread use of asbestos fibers.

Nanotoxicology and nanomedicine make extensive use of in vitro cellular assays that were developed prior to the nanotechnology era. The introduction of nanomaterials to these standard assays causes problems that are currently limiting progress in the field.[1] Nanoparticles are often difficult to disperse;[2] they can interfere with optical measurements through light absorption, and they can interact with dyes used as molecular probes of cellular integrity.[3] In some cases the resulting artifacts can lead to gross misinterpretation of effects on cell viability and cytotoxicity.[4] Because sp2-hybridized carbon materials are near-universal sorbents for organic compounds in aqueous phases, and in light of a recent report of favorable noncovalent interactions between small-aromatic-molecule therapeutic agents and single-walled carbon nanotubes (SWNTs),[5] we hypothesize that SWNTs will adsorb a wide variety of small organic solutes from biological media, not limited to indicator dyes or their water-insoluble reduction products.

The world-wide nanotechnology movement is devoting a rapidly growing literature on biological interactions of carbon nanotubes (CNTs), however the conflicting data have emerged about the biocompatibility and toxicity of carbon nanotubes, and there is no consensus on the overall risk to human health (Hurt et al., 2006; Smart et al., 2006). To resolve this issue, further study is needed, with particular emphasis on understanding the material features of carbon nanotubes, such as size, shape, surface chemistry, and metals content, and we hypothesize that some of the conflicting toxicity data are due to real sample-to-sample variation in these material properties. It is also unclear whether carbon nanotube catalyst residues can trigger these toxicity mechanisms due to apparent encapsulation of the nickel within carbon shells. Nickel, the majority component in Ni-Y catalysts commonly used in the commercial synthesis of single-wall nanotubes (SWNTs) (Journet et al. 1997), is an established human carcinogen that induces gene silencing and hypoxia signaling through mechanisms involving intracellular nickel cation. The early toxicology literature includes nickle effects in SWNT by Lam et al, nickel nanoparticles and mostly nickel compounds such as nickel subsulfide (Lam et al. 2004; Zhang et al. 1998; Costa et al. 2005). Models of nickel induced respiratory tumors suggests that cellular bioavailability of nickel (the delivery of Ni (II) ions to the nucleus of target epithelial cells) is the major determinant for the carcinogenicity of nickel. A key material science question, therefore, is whether sufficient Ni (II) ion can be released from CNT samples. Moreover, the ability of various nickel compounds to be taken up by cells directly influences intracellular nickel levels, and their carcinogenic activity is proportional to cellular uptake(Oller et al., 1997; Costa et al., 1980). Soluble nickel ions can be transported directly, and insoluble or relatively insoluble nickel compounds can be taken up as particles by endocytosis or phagocytosis. Phagocytosis/endocytosis of poorly soluble nickel compounds such as Ni

Purpose: The purpose of this study was to evaluate if a commercial implementation of Knowledge Based Planning (KBP) software can be used to estimate Dose Volume Histogram (DVHs) on a comprehensive data set of Head and Neck (HN) patients. Methods: KBP is a tool capable of estimating DVHs for Organs At Risk (OARs) based on the DVHs of plans of similar patients treated in the past. This study used a newly developed commercial implementation of KBP to create a HN model. The model was trained using a database of retrospectively treated HN patients. This database covered the spectrum of cases expected to be found in the clinic, including multiple targets and 18 different dose prescription combinations. A set of independent validation patients was used to quantify the accuracy of DVHs estimated using the model and covered the same spectrum of HN cases. Results: The accuracy of the model was calculated by comparing the volumes of the estimated and clinical DVHs at doses equal to 50%, 85% and 99% of the maximum OAR dose. This allowed us to quantify the accuracy of the estimated DVHs even in cases when the OAR was receiving a low dose. The highest accuracy was obtained in the estimation of the DVHs for the Brain (

Silica particles are toxic to primary cultures of macrophages or the P388D1 cell line in vitro. Loss of viability in these model systems is accompanied by depletion of ATP content within 3 to 6 hours. The mechanisms responsible for ATP depletion will be explored in this paper. After prelabeling for 1 hour with 3H-adenine, silica-treated cells released 60-80% of their labeled acid-soluble pool into the culture medium. This release did not occur after phagocytosis of nontoxic titanium dioxide particles and was specific for purines. ATP depletion was accompanied by purine catabolism: inosine, hypoxanthine, xanthine, and uric acid were detected in the culture medium using thin layer or high-performance liquid chromatography. The final xanthine oxidase step in purine catabolism generates reactive oxygen metabolites. Silica toxicity was not prevented by the xanthine oxidase inhibitor allopurinol nor exogenous purines. It is concluded that adenine nucleotide depletion and purine catabolism are not solely responsible for irreversible injury in silica toxicity. It is hypothesized that purine catabolism and release from injured macrophages may lead to generation of reactive oxygen species, injury to surrounding tissue, and fibrosis.

Rat peritoneal macrophages were studied for their ability to undergo metabolic cooperation with rat fibroblasts or with other macrophages. In contrast, rat reticular cells, mesothelial cells, and fibroblasts were able to cooperate with human fibroblasts.