Presynaptic Rac1 in the hippocampus selectively regulates working memory.

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory is selectively impaired following the expression of a genetically encoded Rac1-inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

Rey-Osterrieth complex figure normative data for the psychiatric population.

Objective: Appropriate normative data are crucial for competent neuropsychological assessment. Although individuals with psychiatric illness often perform more poorly than healthy adults on neuropsychological testing, data that reflect the psychiatric population are often lacking. We present a normative dataset and calculation tools for the Rey-Osterrieth Complex Figure Test (RCFT) derived from the psychiatric inpatient population. Method: A sample of 301 psychiatric inpatients completed the RCFT and the Test of Memory Malingering (TOMM) between 1999 and 2018. Participants were 59.5% male, 82.1% Caucasian, 13.3% black, and 4.6% identified as another racial demographic, largely consistent with recent Substance Abuse and Mental Health Services Administration (2018) data for inpatients in U.S. psychiatric facilities. Scores for RCFT Copy, Short-Delay Free Recall, Long-Delay Free Recall, Total Recognition, and Percent Retained were modeled via multiple regression with age and education as predictors. Base rates were computed for subscores comprising Total Recognition to aid clinical decision making. Results: Age and education served as significant individual predictors for all models except one model predicting percent retained across delay that included only age. Regression equations and regression standard errors were used to produce a score calculator using a commonly available spreadsheet software package. Healthy adult norms under-estimated performance in our sample, underscoring the importance of these normative data. Conclusions: These normative data for the RCFT represent a large cohort of psychiatric inpatients. For clinical practice and research, both the data and the tools provided are likely to be of particular usefulness among individuals with serious mental illness.

Gender dynamics in the donation field: human tissue donation for research, therapy and feeding.

This paper examines how gender dynamics shape human tissue donation for research and for human health. Drawing on research investigating the donation of different types of bodily tissues including blood, plasma, breastmilk, cord blood, foetal tissue and placentae we consider how and why women and men are viewed as different kinds of donors. We situate these donation practices within a broader understanding of gender difference to explain why any sociology of donation needs to take account of gender. In so doing we explore how tissue derived from the bodies of women acquires value in distinctive ways and for distinctive purposes and reasons. Within these gendered bioeconomies of donation, the supply and demand for tissue is structured by social understandings of maternity, parental responsibility, and risk, which in turn affect the experiences of donors.

Cognitive functioning and adjudicative competence: defendants referred for neuropsychological evaluation in a psychiatric inpatient setting.

OBJECTIVE: A paucity of peer-reviewed research exists regarding the relation between cognitive functioning and adjudicative competence, despite increasing awareness of cognitive deficits associated with serious mental illness. This retrospective study sought to add to and expand upon existing research by considering performance validity and court determinations of competence, when available. METHOD: We compared demographic and cognitive variables of a group of defendants with presumed valid testing admitted to an inpatient psychiatric facility for evaluation of adjudicative competence and referred for neuropsychological evaluation (n = 45) and compared individuals determined by the evaluator and/or the court to be competent (n = 30) and incompetent (n = 15). RESULTS: Defendants who were incompetent were more likely to be diagnosed with a cognitive disorder, with a medium effect size. There was a difference in tests of immediate and delayed memory as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), with medium to large effects, and high delayed memory scores were helpful in ruling out incompetence (Negative predictive power = 85.71%). CONCLUSIONS: These results provide support for the relationship between cognitive functioning and trial competence, particularly at high and low levels of performance.

Risky Bodies in the Plasma Bioeconomy: A Feminist Analysis.

In 2003 the UK National Blood Service introduced a policy of 'male donor preference' which involved women's plasma being discarded following blood collection. The policy was based on the view that data relating to the incidence of Transfusion-Related Acute Lung Injury (TRALI) was linked to transfusion with women's plasma. While appearing to treat female donors as equal to male donors, exclusion criteria operate after donation at the stage of processing blood, thus perpetuating myths of universality even though only certain 'extractions' from women are retained for use in transfusion. Many women in the UK receive a plasma-derived product called Anti-D immunoglobulin which is manufactured from pooled male plasma. This article examines ways in which gender has significance for understanding blood relations, and how the blood economy is gendered. In our study of relations between blood donors and recipients, we explore how gendered bodies are produced through the discursive and material practices within blood services. We examine both how donation policies and the manufacturing and use of blood products produces gendered blood relations.

Origin stories from a regional placenta tissue collection.

Twenty-three years ago when women and their children were recruited to a longitudinal genetic epidemiological study during pregnancy, placentas were collected at birth. This paper explores the history of a regional placenta biobank and contemporary understandings of its value for the constitution of a research population. We draw on interviews with some of the mothers and those responsible for the establishment and curation of the placenta collection in order to explore the significance and meaning of the collection for them. Given its capacity to stand in for the study cohort of mothers and children, we argue that the material significance of the placenta biobank as a research tool seems far less important than the work it does in constituting a population. The stories about this collection may be understood within the wider context of developments in biobanking and the bioeconomy.

Clinical decision making in response to performance validity test failure in a psychiatric setting.

This study examined the clinical utility of a performance validity test (PVT) for screening consecutive referrals (N = 436) to a neuropsychology service at a state psychiatric hospital treating both civilly committed and forensic patients. We created a contingency table with Test of Memory Malingering (TOMM) pass/fail (355/81) and secondary gain present/absent (181/255) to examine pass rates associated with patient demographic, clinical and forensic status characteristics. Of the 81 failed PVTs, 48 had secondary gain defined as active criminal legal charges; 33 failed PVTs with no secondary gain. These individuals tended to be older, female, Caucasian, and civilly committed compared with the group with secondary gain who failed. From estimations of TOMM False Positive Rate and True Positive Rate we estimated base rates of neurocognitive malingering for our clinical population using the Test Validation Summary (TVS; Frederick & Bowden, 2009 ). Although PVT failure is clearly more common in a group with secondary gain (31%), there were a number of false positives (11%). Clinical ratings of patients without gain who failed suggested cognitive deficits, behavioral issues, and inattention. Low scores on PVTs in the absence of secondary gain provide useful information on test engagement and can inform clinical decisions about testing.

Routine administration of Anti-D: the ethical case for offering pregnant women fetal RHD genotyping and a review of policy and practice.

BACKGROUND: Since its introduction in the 1960s Anti-D immunoglobulin (Anti-D Ig) has been highly successful in reducing the incidence of haemolytic disease of the fetus and newborn (HDFN) and achieving improvements to maternal and fetal health. It has protected women from other invasive interventions during pregnancy and prevented deaths and damage amongst newborns and is a technology which has been adopted worldwide. Currently about one third of pregnant women with the blood group Rhesus D (RhD) negative in the UK (approximately 40,000 women per year in England and Wales), receive antenatal Anti-D Ig in pregnancy when they do not require it because they are carrying a RhD negative fetus. Since 1997, a test using cell free fetal DNA (cffDNA) in maternal blood has been developed to identify the genotype of the fetus and can be used to predict the fetal RhD blood group. DISCUSSION: This paper considers whether it is ethically acceptable to continue administering antenatal Anti-D Ig to all RhD negative women when fetal RHD genotyping using maternal blood could identify those women who do not need this product. SUMMARY: The antenatal administration of Anti-D Ig to a third of RhD negative pregnant women who carry a RhD negative fetus and therefore do not need it raises important ethical issues. If fetal RHD genotyping using maternal blood was offered to all RhD negative pregnant women it would assist them to make an informed choice about whether or not to have antenatal Anti-D Ig.

Revaluing donor and recipient bodies in the globalised blood economy: transitions in public policy on blood safety in the United Kingdom.

The clinical use of blood has a long history, but its apparent stability belies the complexity of contemporary practices in this field. In this article, we explore how the production, supply and deployment of blood products are socially mediated, drawing on theoretical perspectives from recent work on 'tissue economies'. We highlight the ways in which safety threats in the form of infections that might be transmitted through blood and plasma impact on this tissue economy and how these have led to a revaluation of donor bodies and restructuring of blood economies. Specifically, we consider these themes in relation to the management of recent threats to blood safety in the United Kingdom. We show that the tension between securing the supply of blood and its products and ensuring its safety may give rise to ethical concerns and reshape relations between donor and recipient bodies.

The fetal tissue economy: from the abortion clinic to the stem cell laboratory.

This paper examines the exchange relationships between women undergoing abortion, the clinicians who procure fetal tissue and stem cell scientists in Britain, and argues that the fetal tissue economy is an important dimension of the gendered bioeconomy that underpins stem cell science. In so doing it suggests that the path from the abortion clinic to the stem cell laboratory differs from the route taken by pre-implantation embryos from the in vitro fertilisation clinic in important ways. It reports on a study which included 29 in-depth, semi-structured interviews with stem cell scientists, policymakers, clinicians, activists and sponsors of stem cell research. The paper explores the meanings attached to aborted fetuses and how women's relationship to fetal tissue is constructed in the interviews, the law and official guidance on the use and disposal of fetal tissue. This is linked to variability in consent procedures and procurement practices.

Purity and the dangers of regenerative medicine: regulatory innovation of human tissue-engineered technology.

This paper examines the development of innovation in human tissue technologies as a form of regenerative medicine, firstly by applying 'pollution ideas' to contemporary trends in its risk regulation and to the processes of regulatory policy formation, and secondly by analysing the classificatory processes deployed in regulatory policy. The analysis draws upon data from fieldwork and documentary materials with a focus on the UK and EU (2002-05) and explores four arenas: governance and regulatory policy; commercialisation and the market; 'evidentiality' manifest in evidence-based policy; and publics' and technology users' values and ethics. The analysis suggests that there is a trend toward 'purification' across these arenas, both material and socio-political. A common process of partitioning is found in stakeholders' attempts to define a clear terrain, which the field of tissue-engineered technology might occupy. We conclude that pollution ideas and partitioning processes are useful in understanding regulatory ordering and innovation in the emerging technological zone of human tissue engineering.

Regulating Hybrids: 'Making a Mess' and 'Cleaning Up' in Tissue Engineering and Transpecies Transplantation.

This paper explores the institutional regulation of novel biosciences, hybrid technologies that often disturb and challenge existing regulatory frameworks. Developing a conceptual vocabulary for understanding the relationship between material and institutional hybrids, the paper compares human tissue engineering (TE) and xenotransplantation (XT), areas of innovation which regulators have sought to govern separately and in isolation from one another. Contrasting definitional boundaries and regulatory mechanisms partition them socio-institutionally. But despite these attempts at purification, TE and XT have proven increasingly difficult to tell apart in practical and material terms. Human and animal matters, cell cultures and tissue products have much greater corporeal connection than has been institutionally recognized, and are therefore a source of acute instability in the regulation of implants and transplants. This paper tells the story of how the messy worlds of TE and XT have leaked into one another, calling into question the abilities of regulation to adequately control hybrid innovations.

Lay experts and the politics of breast implants.

This paper discusses the controversy around breast implants in the United States and Europe. It focuses on the emergence of consumer and support groups for women and offers an analysis of the role they have played in recent policy developments in UK and Europe. The politics of breast implants is seen as a politics of knowledge in which scientific expertise has consistently been deployed in ways that minimize the credibility and legitimacy of women's accounts of their bodies and illness experiences. These women have been doubly disadvantaged in a policy debate that turns on scientific controversy and uncertainty. This implies a gendered dynamic to the changing relations of knowledge and expertise. The paper contributes to an understanding of the relations between regulators, manufacturers, users, and clinicians in the global medical device industry and to wider debates around the public understanding of science.