Fear and fitness: An evolutionary analysis of anxiety disorders

This article reviews the evolutionary origins and functions of the capacity for anxiety, and relevant clinical and research issues. Normal anxiety is an emotion that helps organisms defend against a wide variety of threats. There is a general capacity for normal defensive arousal, and subtypes of normal anxiety protect against particular kinds of threats. These normal subtypes correspond somewhat to mild forms of various anxiety disorders. Anxiety disorders arise from dysregulation of normal defensive responses, raising the possibility of a hypophobic disorder (too little anxiety). If a drug were discovered that abolished all defensive anxiety, it could do harm as well as good. Factors that have shaped anxiety-regulation mechanisms can explain prepotent and prepared tendencies to associate anxiety more quickly with certain cues than with others. These tendencies lead to excess fear of largely archaic dangers, like snakes, and too little fear of new threats, like cars. An understanding of the evolutionary origins, functions, and mechanisms of anxiety suggests new questions about anxiety disorders.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31354/1/0000265.pd

Integrated analysis of the molecular action of Vorinostat identifies epi-sensitised targets for combination therapy

Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment. Direct targeting of the SHH pathway with SANT-1, following Vorinostat induced epi-sensitisation, resulted in synergistic cell death of AML cells. In addition, xenograft studies demonstrated that combination therapy induced a marked reduction in leukemic burden compared to control or single agents. Together, the data supports epi-sensitisation as a potential component of the strategy for the rational development of combination therapies in AML

Ages of onset of DSM-III anxiety disorders

The Diagnostic and Statistical Manual (DSM-III) contains little specific information pertaining to the ages of onset of anxiety disorders. Such information is of clinical and research value in understanding the natural history of mental illnesses, in determining which of several possible etiologies for a given diagnosis may be relevant for a particular patient, and in testing theories of psychopathology or pathophysiology. Age-of-onset data is presented for 423 psychiatric outpatients seen at a University Hospital--based anxiety disorders program. All adult anxiety disorders are represented except posttraumatic stress disorder. The relevance of this information is discussed in terms of past research on ages of onset of the anxiety disorders, and in its bearing on the psychiatric diagnosis of these conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25743/1/0000303.pd

An evolutionary perspective on substance abuse

This article describes how recent advances in understanding the evolutionary functions of emotions can help to reconcile diverse approaches to substance abuse. Emotions can be understood as specialized states that prepare individuals to cope with opportunities and threats. Drugs that artificially induce pleasure or block normal suffering disrupt these evolved mechanisms, and thus should tend to interfere with adaptive behavior, even if the drugs are medically safe. Nonetheless, we routinely use drugs quite safely to block defenses like pain, cough, and anxiety. This apparent contradiction is explained by the relatively small costs of defenses compared to the potentially huge costs of not expressing a defensive response when it is needed. An evolutionary perspective has implications for substance abuse research, treatment, and social policy. This perspective suggests that the search for etiology needs to address the human tendency to abuse drugs separately from individual differences in these tendencies, that clinical treatments that take account of the broad range of patients' emotional life are well justified, and that social policies need to address substance use and abuse not as diseases to be cured but as human tendencies that need to be managed. To prepare for future drugs that will likely alter emotions safely, we urgently need a better understanding of the adaptive function of the emotions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31367/1/0000279.pd

Male gays in the female gaze: women who watch m/m pornography

This paper draws on a piece of wide-scale mixed-methods research that examines the motivations behind women who watch gay male pornography. To date there has been very little interdisciplinary research investigating this phenomenon, despite a recent survey by PornHub (one of the largest online porn sites in the world) showing that gay male porn is the second most popular choice for women porn users out of 25+ possible genre choices. While both academic literature and popular culture have looked at the interest that (heterosexual) men have in lesbian pornography, considerably less attention has been paid to the consumption of gay male pornography by women. Research looking at women's consumption of pornography from within the Social Sciences is very focused around heterosexual (and, to a lesser extent, lesbian) pornography. Research looking more generally at gay pornography/erotica (and the subversion of the ‘male gaze’/concept of ‘male as erotic object’) often makes mention of female interest in this area, but only briefly, and often relies on anecdotal or observational evidence. Research looking at women's involvement in slashfic (primarily from within media studies), while very thorough and rich, tends to view slash writing as a somewhat isolated phenomenon (indeed, in her influential article on women's involvement in slash, Bacon-Smith talks about how ‘only a small number’ of female slash writers and readers have any interest in gay literature or pornography more generally, and this phenomenon is not often discussed in more recent analyses of slash); so while there has been a great deal of very interesting research done in this field, little attempt has been made to couch it more generally within women's consumption and use of pornography and erotica or to explore what women enjoy about watching gay male pornography. Through a series of focus groups, interviews, and an online questionnaire (n = 275), this exploratory piece of work looks at what women enjoy about gay male pornography, and how it sits within their consumption of erotica/pornography more generally. The article investigates what this has to say about the existence and nature of a ‘female gaze’

Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4 <sup>+</sup> T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity

Sleeping sickness and its relationship with development and biodiversity conservation in the Luangwa valley, Zambia

The Luangwa Valley has a long historical association with Human African trypanosomiasis (HAT) and is a recognised geographical focus of this disease. It is also internationally acclaimed for its high biodiversity and contains many valuable habitats. Local inhabitants of the valley have developed sustainable land use systems in co-existence with wildlife over centuries, based on non-livestock keeping practices largely due to the threat from African Animal Trypanosomiasis. Historical epidemics of human sleeping sickness have influenced how and where communities have settled and have had a profound impact on development in the Valley. Historical attempts to control trypanosomiasis have also had a negative impact on conservation of biodiversity. Centralised control over wildlife utilisation has marginalised local communities from managing the wildlife resource. To some extent this has been reversed by the implementation of community based natural resource management programmes in the latter half of the 20th century and the Luangwa Valley provides some of the earliest examples of such programmes. More recently, there has been significant uncontrolled migration of people into the mid-Luangwa Valley driven by pressure on resources in the eastern plateau region, encouragement from local chiefs and economic development in the tourist centre of Mfuwe. This has brought changing land-use patterns, most notably agricultural development through livestock keeping and cotton production. These changes threaten to alter the endemically stable patterns of HAT transmission and could have significant impacts on ecosystem health and ecosystem services. In this paper we review the history of HAT in the context of conservation and development and consider the impacts current changes may have on this complex social-ecological system. We conclude that improved understanding is required to identify specific circumstances where win-win trade-offs can be achieved between the conservation of biodiversity and the reduction of disease in the human population.Ecosystem Services for Poverty Alleviation (ESPA