Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.

Acetaminophen (APAP)-induced liver injury is clinically significant, and APAP overdose in mice often serves as a model for drug-induced liver injury in humans. By specifying that APAP metabolism, reactive metabolite formation, glutathione depletion, and mitigation of mitochondrial damage within individual hepatocytes are functions of intralobular location, an earlier virtual model mechanism provided the first concrete multiattribute explanation for how and why early necrosis occurs close to the central vein (CV). However, two characteristic features could not be simulated consistently: necrosis occurring first adjacent to the CV, and subsequent necrosis occurring primarily adjacent to hepatocytes that have already initiated necrosis. We sought parsimonious model mechanism enhancements that would manage spatiotemporal heterogeneity sufficiently to enable meeting two new target attributes and conducted virtual experiments to explore different ideas for model mechanism improvement at intrahepatocyte and multihepatocyte levels. For the latter, evidence supports intercellular communication via exosomes, gap junctions, and connexin hemichannels playing essential roles in the toxic effects of chemicals, including facilitating or counteracting cell death processes. Logic requiring hepatocytes to obtain current information about whether downstream and lateral neighbors have triggered necrosis enabled virtual hepatocytes to achieve both new target attributes. A virtual hepatocyte that is glutathione-depleted uses that information to determine if it will initiate necrosis. When a less-stressed hepatocyte is flanked by at least two neighbors that have triggered necrosis, it too will initiate necrosis. We hypothesize that the resulting intercellular communication-enabled model mechanism is analogous to the actual explanation for APAP-induced hepatotoxicity at comparable levels of granularity

The Many Faces of Risk: A Qualitative Study of Risk in Outpatient Involuntary Treatment.

Objective: This study aimed to derive a conceptualisation of risk in outpatient involuntary psychiatric treatment that has utility and meaning for stakeholders. Methods: Thirty-eight participants –patients, caregivers, clinicians and legal decision makers – participated in qualitative interviews about their experiences of outpatient involuntary psychiatric treatment. Interview data was analysed using a general inductive method. Results: Six types of risk were identified: ‘actual harm’, ‘social adversity’, ‘therapeutic outcome/compromised treatment’, ‘the system’, ‘interpersonal distress’, and ‘epistemic’. There were overlaps between the discourses on risk, but variation in how different aspects of risk were emphasised. Conclusions: Based on the findings, a comprehensive model of “risk” contextualized to outpatient involuntary treatment is proposed. It incorporates the domains of “risk of harm to self or others”; “risk of social adversity”; “risk of excess distress”; and, “risk of compromised treatment”. This model may have instrumental value in the implementation and the scrutiny of risk-based mental health laws.funded by a discretionary grant from the Mental Health, Drug and Alcohol Office of NSW Healt

The lived experience of involuntary community treatment: a qualitative study of mental health consumers and carers

Objective: To describe the lived experiences of people subject to community treatment orders (CTOs) and their carers. Method: We recruited 11 participants (five mental health consumers and six carers) through consumer and carer networks in NSW, Australia, to take part in interviews about their experiences. We analysed the interview data set using established qualitative methodologies. Results: The lived experiences were characterised by ‘access’ concerns, ‘isolation’, ‘loss and trauma’, ‘resistance and resignation’ and ‘vulnerability and distress’. The extent and impact of these experiences related to the severity of mental illness, the support available for people with mental illnesses and their carers, the social compromises associated with living with mental illness, and the challenges of managing the relationships necessitated by these processes. Conclusions: The lived experience of CTOs is complex: it is one of distress and profound ambivalence. The distress is an intrinsic aspect of the experience of severe mental illness, but it also emerges from communication gaps, difficulty obtaining optimal care and accessing mental health services. The ambivalence arises from an acknowledgement that while CTOs are coercive and constrain autonomy, they may also be beneficial. These findings can inform improvements to the implementation of CTOs and the consequent experiences. Keywords: carer, community treatment order, interview, involuntary treatment, mental health, patient experience, qualitative researchsupported by the Mental Health, Drug and Alcohol Office (MHDAO) of NSW Health of Australia

Research encounters, reflexivity and supervision

Reflexivity in qualitative and ethnographic social science research can provide a rich source of data, especially regarding the affective, performative and relational aspects of interviews with research subjects. This paper explores by means of three case examples different ways of accessing and using such reflexivity. The examples are drawn from an empirical psycho-social study into the identity transitions of first-time mothers in an inner-city multicultural environment. Fieldnotes and supervision were used to engage with researcher subjectivity, to enhance the productive use of reflexivity and to address the emotional work of research. The methodology of the supervision was psychoanalytic, in its use of a boundaried frame and of psychoanalytic forms of noticing oneself, of staying engaged emotionally as well as creating a reflective distance. The examples illustrate how this can enhance the knowledge gained about the research subjects

V1647 Orionis: Reinvigorated Accretion and the Re-Appearance of McNeil's Nebula

In late 2003, the young eruptive variable star V1647 Orionis optically brightened by over 5 magnitudes, stayed bright for around 26 months, and then decline to its pre-outburst level. In August 2008 the star was reported to have unexpectedly brightened yet again and we herein present the first detailed observations of this new outburst. Photometrically, the star is now as bright as it ever was following the 2003 eruption. Spectroscopically, a pronounced P Cygni profile is again seen in Halpha with an absorption trough extending to -700 km/s. In the near-infrared, the spectrum now possesses very weak CO overtone bandhead absorption in contrast to the strong bandhead emission seen soon after the 2003 event. Water vapor absorption is also much stronger than previously seen. We discuss the current outburst below and relate it to the earlier event.Comment: 6 pages, 3 figure

Temperature Dependence of Radiation Induced Conductivity in Insulators

We report on measurements of Radiation Induced Conductivity (RIC) of thin film Low Density Polyethylene (LDPE) samples. RIC occurs when incident ionizing radiation deposits energy in a material and excites electrons into conduction states. RIC is calculated as the difference in sample conductivity under an incident flux and “dark current” conductivity under no incident radiation. The primary focus of this study is the temperature dependence of the steady state RIC over a wide range of absorbed dose rates, from cryogenic temperatures to well above room temperature. The measured RIC values are compared to theoretical predictions of dose rate and temperature dependence based on photoconductivity models developed for localized trap states in disordered semiconductors. We also investigated the variation of RIC as a function of material, applied electric field, and incident beam energy parameters