Desire for hastened death in patients with advanced disease and the evidence base of clinical guidelines:a systematic review

Patients' desire for hastened death within the context of advanced disease and palliative care is a controversial topic, frequently discussed in the international literature. Much of the discussion has focused on opinion and debate about ethical matters related to hastened death. Not many research studies seem to have specifically targeted why palliative care patients may desire hastened death, and few have focused on clinical guidelines for responding to such requests.

SAHA overcomes FLIP-mediated inhibition of SMAC mimetic-induced apoptosis in mesothelioma

Malignant pleural mesothelioma (MPM) is a highly pro-inflammatory malignancy that is rapidly fatal and increasing in incidence. Cytokine signaling within the pro-inflammatory tumor microenvironment makes a critical contribution to the development of MPM and its resistance to conventional chemotherapy approaches. SMAC mimetic compounds (SMCs) are a promising class of anticancer drug that are dependent on tumor necrosis factor alpha (TNFa) signaling for their activity. As circulating TNFa expression is significantly elevated in MPM patients, we examined the sensitivity of MPM cell line models to SMCs. Surprisingly, all MPM cell lines assessed were highly resistant to SMCs either alone or when incubated in the presence of clinically relevant levels of TNFa. Further analyses revealed that MPM cells were sensitized to SMC-induced apoptosis by siRNA-mediated downregulation of the caspase 8 inhibitor FLIP, an antiapoptotic protein overexpressed in several cancer types including MPM. We have previously reported that FLIP expression is potently downregulated in MPM cells in response to the histone deacetylase inhibitor (HDACi) Vorinostat (SAHA). In this study, we demonstrate that SAHA sensitizes MPM cells to SMCs in a manner dependent on its ability to downregulate FLIP. Although treatment with SMC in the presence of TNFa promoted interaction between caspase 8 and the necrosis-promoting RIPK1, the cell death induced by combined treatment with SAHA and SMC was apoptotic and mediated by caspase 8. These results indicate that FLIP is a major inhibitor of SMC-mediated apoptosis in MPM, but that this inhibition can be overcome by the HDACi SAHA. © 2013 Macmillan Publishers Limited All rights reserved.

Queer Spaces, Sexual Violence and the Desire for Safety

Queer politics and spaces have historically been associated with ideals of sexual liberation. They are conceptualised as spaces where sex, and its intersections with intimacy, friendship and love can be explored outside of normative frameworks which value monogamous reproductive heterosexuality at the expense of other non-normative sexual expressions. In recent years, however, autonomous queer spaces such as the global Queeruption gatherings and other queer community spaces in Australia have become increasingly concerned with the presence and danger of sexual violence in queer communities. Almost without exception, this danger has been responded to through the creation of ‘safe(r) spaces’ policies, generally consisting of a set of guidelines and proscribed behaviours which individuals must agree to in order to participate in or attend the event or space. The guidelines themselves tend to privilege of sexual politics of affirmative verbal consent, insisting that such consent should be sought prior to any physical or sexual contact, inferring that a failure to do so is ethically unacceptable within. This chapter reflects on the attempts to construct queer communities as ‘safer spaces,’ arguing that the concepts of consent and safety are inadequate to develop a queer response to sexual violence. Such a response, it argues, must be based on the openness to possibilities and refusal of sexual restrictions and regulations that have always been central elements of queer theory and politics.

Desire for fertility and associated factors among people living with HIV/AIDS (PLWHA) in selected antiretroviral therapy (ART) clinics of Horro Guduru Wollega Zone, North West Oromia, Ethiopia- A cross sectional study

Background: Most recently fertility issues in HIV positive men and women are becoming increasingly important. Because of ART access and its good life effect, it is expected that the need and desire to get married, to have children and to have sexual partners for PLWHA would change with the regard to reproductive health. In Ethiopia HIV positive individuals may or may not have desire to have children. And the extent of this desire and how it varies by individual, health and demographic characteristics is not well known.

Objective: the aim of the study was to assess desire for fertility and associated factors among PLWHA in selected ART clinics of Horro Guduru Wollega Zone, Oromia National Regional State, Ethiopia.

Methods: A cross-sectional, institutional-based study that employed quantitative and qualitative in-depth interviews was conducted. Three hundred twenty one study subjects were selected using systematic random sampling technique and the data was collected using interviewer administered structured questionnaire. Data entry and analysis were performed using EPI Info version 3.5.1 and SPSS version 16. P-value <0.05 was taken as statistically significant and logistic regression was used to control potential confounding factors.

Results: Seventy three (57.9%) of the males and seventy six (39%) of the females desired to have children, giving a total of 149(46.4%) of all study participants. PLWHA who desired children were younger (AOR:3.3, 95%CI: 1.3-8.9), married (AOR: 5.8, 95%CI: 2.7-12.8), had no children (AOR: 75, 95%CI: 20.1-273.3) and males (AOR; 1.9, 95%CI: 1.02-3.62) compared with their counter parts. The major reason for those people who did not desire children were having desired number of children 80 (46.5%) followed by fear of HIV transmission to child reported by 42 (24.4%) of them.

Conclusion: A considerable number of PLWHA wants to have a child currently or in the near future. Many variables like socio demography, partner related, number of alive children and HIV related disease condition were significantly associated with fertility desire.

β-Strand mimetic foldamers rigidified through dipolar repulsion

Many therapeutically relevant protein-protein interactions contain hot-spot regions on secondary structural elements, which contribute disproportionately to binding enthalpy. Mimicry of such α-helical regions has met with considerable success, however the analogous approach for the β-strand has received less attention. Presented herein is a foldamer for strand mimicry in which dipolar repulsion is a central determinant of conformation. Computation as well as solution- and solid-phase data are consistent with an ensemble weighted almost exclusively in favor of the desired conformation.

Desire and Divorce in Serglige Con Culainn

This paper examines the expression of ideas about love, marriage and divorce in Serglige Con Culainn. It is argued that the two versions of the tale, both of which are incomplete, exhibit distinctive approaches to love and the portrayal of the female characters. The earlier recension depicts male desire as a violent attack by Otherworld women that renders the man incapacitated. The later version provides a radically different view, offering a strikingly sympathetic portrait of the two female protagonists which may suggest a female audience. This version gives a remarkable insight into sexual mores and marital breakdown in a protracted and detailed negotiation involving the three main characters. It reveals tensions between male and female views of marriage and particularly of the practice of concubinage. It values loyalty between married partners over the fulfilment of desire and demonstrates the enduring and destructive effects of passion which are healed here only through magical interventions.

Do people with diabetes who need to talk want to talk?

Aim. To examine whether the people with diabetes who ask for psychological support are those who are experiencing clinically significant levels of psychological distress.
Method. In total 300 people with diabetes were asked to complete psychometrically validated questionnaires that assessed subjective need and objective psychological distress.
Results. High levels of psychological distress were reported: 25% of the sample reported depressive symptomatology, 41% reported clinically significant levels if anxiety and 51% reported a degree of binge eating behaviour. Participants also indicated a desire to talk to diabetes professionals about various problem areas in diabetes. Chi-square analysis demonstrated that those reporting psychological distress, especially depression, were most likely to indicate a desire to talk to somebody about living with diabetes.
Conclusions. Those who want to talk are those who need to talk. Future service development issues should acknowledge the needs and expressed wishes of service users.

'National Antiquities' and the Law

National museums, housing â??national antiquities', were a nineteenth-century cultural phenomenon throughout Europe. In the United Kingdom, they afforded the Treasury a means of preserving relics of antiquity claimed as treasure trove. While satisfying the desire of the scientific community for the preservation of archaeological finds, and national sentiment in Scotland and Ireland, Treasury practice undermined the British Museum's eponymous mission. This paper traces the development and legal consequences of the Treasury policy of national allocation of treasure trove, including the discussion in the Museums Committee of 1898â??99 of the â??nationality' of objects and artefacts, and considers the potential wider significance of â??national antiquity' in the context of changing constitutional arrangements in the United Kingdom in the 1920s, and in the future.