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As a cellular signaling program, apoptosis is a highly controlled and complex process that depends on the orchestrated interactions of multiple soluble factors: ions (e.g., Ca2+), proteins (e.g., caspases, Bcl-2 family members), and nonprotein substrates (e.g., DNA). Equally important, although less well characterized, is signaling through cellular membranes and the lipids and proteins contained therein. Lipids are the primary constituents of biological membranes and thus play a structural role in defining cellular and organellar boundaries. However, lipids are not merely passive molecules serving inert, structural functions in these membranes. Many lipids are now appreciated as signaling molecules, capable of influencing diverse cellular processes and exerting powerful influence over many physiologic and pathophysiologic processes, such as programmed cell death. Sphingolipids represent one class of bioactive lipid mediators that are now recognized as key determinants of cell fate. This chapter discusses the regulated generation of bioactive sphingolipids (e.g., ceramide) and how sphingolipid signaling impacts the regulation of programmed cell death.
Mental health clinicians are frequently asked to assess the risks presented by patients making threats to kill, but there are almost no data to guide such an evaluation.
This data linkage study examined serious violence following making threats to kill and the potential role of mental disorder. A total of 613 individuals convicted of threats to kill had their prior contact with public mental health services established at the time of the index offence. The group's subsequent criminal convictions were established 10 years later using the police database. Death from suicidal or homicidal violence was also established.
Within 10 years, 44% of threateners were convicted of further violent offending, including 19 (3%) homicides. Those with histories of psychiatric contact (40%) had a higher rate (58%) of subsequent violence. The highest risks were in substance misusers, mentally disordered, young, and those without prior criminal convictions. Homicidal violence was most frequent among threateners with a schizophrenic illness. Sixteen threateners (2.6%) killed themselves, and three were murdered.
In contrast to the claims in the literature that threats are not predictive of subsequent violence, this study revealed high rates of assault and even homicide following threats to kill. The mentally disordered were over-represented among threat offenders and among those at high risk of subsequent violence. The mentally disordered threateners at highest risk of violence were young, substance abusing, but not necessarily with prior convictions. Those who threaten others were also found to be at greater risk of killing themselves or being killed.
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