Using genetic algorithms to uncover individual differences in how humans represent facial emotion

Emotional facial expressions critically impact social interactions and cognition. However, emotion research to date has generally relied on the assumption that people represent categorical emotions in the same way, using standardized stimulus sets and overlooking important individual differences. To resolve this problem, we developed and tested a task using genetic algorithms to derive assumption-free, participant-generated emotional expressions. One hundred and five participants generated a subjective representation of happy, angry, fearful and sad faces. Population-level consistency was observed for happy faces, but fearful and sad faces showed a high degree of variability. High test-retest reliability was observed across all emotions. A separate group of 108 individuals accurately identified happy and angry faces from the first study, while fearful and sad faces were commonly misidentified. These findings are an important first step towards understanding individual differences in emotion representation, with the potential to reconceptualize the way we study atypical emotion processing in future research

A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC-derived microglia

Loss‐of‐function genetic variants of triggering receptor expressed on myeloid cells 2 (TREM2) are linked with an enhanced risk of developing dementias. Microglia, the resident immune cell of the brain, express TREM2, and microglial responses are implicated in dementia pathways. In a normal surveillance state, microglia use oxidative phosphorylation for their energy supply, but rely on the ability to undergo a metabolic switch to glycolysis to allow them to perform rapid plastic responses. We investigated the role of TREM2 on the microglial metabolic function in human patient iPSC‐derived microglia expressing loss of function variants in TREM2. We show that these TREM2 variant iPSC‐microglia, including the Alzheimer's disease R47H risk variant, exhibit significant metabolic deficits including a reduced mitochondrial respiratory capacity and an inability to perform a glycolytic immunometabolic switch. We determined that dysregulated PPARγ/p38MAPK signaling underlies the observed phenotypic deficits in TREM2 variants and that activation of these pathways can ameliorate the metabolic deficit in these cells and consequently rescue critical microglial cellular function such as β‐Amyloid phagocytosis. These findings have ramifications for microglial focussed‐treatments in AD

Microglial signalling pathway deficits associated with the patient derived R47H TREM2 variants linked to AD indicate inability to activate inflammasome

The R47H variant of the microglial membrane receptor TREM2 is linked to increased risk of late onset Alzheimer's disease. Human induced pluripotent stem cell derived microglia (iPS-Mg) from patient iPSC lines expressing the AD-linked R47Hhet TREM2 variant, common variant (Cv) or an R47Hhom CRISPR edited line and its isogeneic control, demonstrated that R47H-expressing iPS-Mg expressed a deficit in signal transduction in response to the TREM2 endogenous ligand phosphatidylserine with reduced pSYK-pERK1/2 signalling and a reduced NLRP3 inflammasome response, (including ASC speck formation, Caspase-1 activation and IL-1beta secretion). Apoptotic cell phagocytosis and soluble TREM2 shedding were unaltered, suggesting a disjoint between these pathways and the signalling cascades downstream of TREM2 in R47H-expressing iPS-Mg, whilst metabolic deficits in glycolytic capacity and maximum respiration were reversed when R47H expressing iPS-Mg were exposed to PS+ expressing cells. These findings suggest that R47H-expressing microglia are unable to respond fully to cell damage signals such as phosphatidylserine, which may contribute to the progression of neurodegeneration in late-onset AD

Liaison Old Age Psychiatry Service in a Medical Setting: Description of the Newcastle Clinical Service

Liaison Old Age Psychiatry services (LOAP) have begun to emerge in the UK and further development of the service is supported by the latest health policies. Since qualitative and quantitative studies in this area are lacking, we have undertaken a detailed quantitative prospective review of referrals to the Newcastle LOAP to evaluate the clinical activity of the service. We report high referral rates and turnover for the LOAP service. Reasons for referral are diverse, ranging from requests for level of care and capacity assessments and transfer to other clinical services to management of behaviour, diagnosis, and treatment. We outline the value of a multidisciplinary model of LOAP activity, including the important role of the liaison nursing team, in providing a rapid response, screening, and followup of high number of clinical referrals to the service

Liaison Old Age Psychiatry Service in a Medical Setting: Description of the Newcastle Clinical Service

Liaison Old Age Psychiatry services (LOAP) have begun to emerge in the UK and further development of the service is supported by the latest health policies. Since qualitative and quantitative studies in this area are lacking, we have undertaken a detailed quantitative prospective review of referrals to the Newcastle LOAP to evaluate the clinical activity of the service. We report high referral rates and turnover for the LOAP service. Reasons for referral are diverse, ranging from requests for level of care and capacity assessments and transfer to other clinical services to management of behaviour, diagnosis, and treatment. We outline the value of a multidisciplinary model of LOAP activity, including the important role of the liaison nursing team, in providing a rapid response, screening, and followup of high number of clinical referrals to the service

Implementation of a standardized protocol to manage elderly patients with low energy pelvic fractures: can service improvement be expected?

Purpose: The incidence of low energy pelvic fractures (FPFs) in the elderly is increasing. Comorbidities, decreased bone-quality, problematic fracture fixation and poor compliance represent some of their specific difficulties. In the absence of uniform management, a standard operating procedure (SOP) was introduced to our unit, aiming to improve the quality of services provided to these patients. Methods: A cohort study was contacted to test the impact of (1) using a specific clinical algorithm and (2) using different antiosteoporotic drugs. Multivariate regression analysis was used to determine prognostic factors. Study endpoints were the time-to-healing, length-of-stay, return to pre-injury mobility, union status, mortality and complications. Results: A total of 132 elderly patients (≥65 years) admitted during the period 2012–2014 with FPFs were enrolled. High-energy fractures, acetabular fractures, associated trauma affecting mobility, pathological pelvic lesions and operated FPFs were used as exclusion criteria. The majority of included patients were females (108/132; 81.8%), and the mean age was 85.8 years (range 67–108). Use of antiosteoporotics was associated with a shorter time of healing (p = 0.036). Patients treated according to the algorithm showed a significant protection against malunion (p < 0.001). Also, adherence to the algorithm allowed more patients to return to their pre-injury mobility status (p = 0.039). Conclusions: The use of antiosteoporotic medication in elderly patients with fragility pelvic fractures was associated with faster healing, whilst the adherence to a structured clinical pathway led to less malunions and non-unions and return to pre-injury mobility state

The PI3K p110δ regulates expression of CD38 on regulatory T cells.

The PI3K pathway has emerged as a key regulator of regulatory T cell (Treg) development and homeostasis and is required for full Treg-mediated suppression. To identify new genes involved in PI3K-dependent suppression, we compared the transcriptome of WT and p110δ(D910A) Tregs. Among the genes that were differentially expressed was the gene for the transmembrane cyclic ADP ribose hydrolase CD38. Here we show that CD38 is expressed mainly by a subset of Foxp3(+)CD25(+)CD4(+) T cells originating in the thymus and on Tregs in the spleen. CD38(high) WT Tregs showed superior suppressive activity to CD38(low) Tregs, which failed to upregulate CD73, a surface protein which is important for suppression. However, Tregs from heterozygous CD38(+/-) mice were unimpaired despite lower levels of CD38 expression. Therefore, CD38 can be used as a marker for Tregs with high suppressive activity and the impaired Treg function in p110δ(D910A) mice can in part be explained by the failure of CD38(high) cells to develop