The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular Disease

Cardiovascular disease is the leading cause of death. The disease is due to atherosclerosis which is characterized by lipid and fat accumulation in arterial blood vessel walls. A key causative event is the accumulation of oxidised low density lipoprotein particles within vascular cells, and this is mediated by scavenger receptors. One such molecule is the LOX-1 scavenger receptor that is expressed on endothelial, vascular smooth muscle, and lymphoid cells including macrophages. LOX-1 interaction with OxLDL particles stimulates atherosclerosis. LOX-1 mediates OxLDL endocytosis via a clathrin-independent internalization pathway. Transgenic animal model studies show that LOX-1 plays a significant role in atherosclerotic plaque initiation and progression. Administration of LOX-1 antibodies in cellular and animal models suggest that such intervention inhibits atherosclerosis. Antiatherogenic strategies that target LOX-1 function using gene therapy or small molecule inhibitors would be new ways to address the increasing incidence of vascular disease in many countries

Authors' Response to Peer Reviews of “Using Structural Equation Modelling in Routine Clinical Data on Diabetes and Depression: Observational Cohort Study”

Background: Large data sets comprising routine clinical data are becoming increasingly available for use in health research. These data sets contain many clinical variables that might not lend themselves to use in research. Structural equation modelling (SEM) is a statistical technique that might allow for the creation of “research-friendly” clinical constructs from these routine clinical variables and therefore could be an appropriate analytic method to apply more widely to routine clinical data. Objective: SEM was applied to a large data set of routine clinical data developed in East London to model well-established clinical associations. Depression is common among patients with type 2 diabetes, and is associated with poor diabetic control, increased diabetic complications, increased health service utilization, and increased health care costs. Evidence from trial data suggests that integrating psychological treatment into diabetes care can improve health status and reduce costs. Attempting to model these known associations using SEM will test the utility of this technique in routine clinical data sets. Methods: Data were cleaned extensively prior to analysis. SEM was used to investigate associations between depression, diabetic control, diabetic care, mental health treatment, and Accident & Emergency (A&E) use in patients with type 2 diabetes. The creation of the latent variables and the direction of association between latent variables in the model was based upon established clinical knowledge. Results: The results provided partial support for the application of SEM to routine clinical data. Overall, 19% (3106/16,353) of patients with type 2 diabetes had received a diagnosis of depression. In line with known clinical associations, depression was associated with worse diabetic control (β=.034, P<.001) and increased A&E use (β=.071, P<.001). However, contrary to expectation, worse diabetic control was associated with lower A&E use (β=–.055, P<.001) and receipt of mental health treatment did not impact upon diabetic control (P=.39). Receipt of diabetes care was associated with better diabetic control (β=–.072, P<.001), having depression (β=.018, P=.007), and receiving mental health treatment (β=.046, P<.001), which might suggest that comprehensive integrated care packages are being delivered in East London. Conclusions: Some established clinical associations were successfully modelled in a sample of patients with type 2 diabetes in a way that made clinical sense, providing partial evidence for the utility of SEM in routine clinical data. Several issues relating to data quality emerged. Data improvement would have likely enhanced the utility of SEM in this data set

A data-driven framework for neural field modeling

This paper presents a framework for creating neural field models from electrophysiological data. The Wilson and Cowan or Amari style neural field equations are used to form a parametric model, where the parameters are estimated from data. To illustrate the estimation framework, data is generated using the neural field equations incorporating modeled sensors enabling a comparison between the estimated and true parameters. To facilitate state and parameter estimation, we introduce a method to reduce the continuum neural field model using a basis function decomposition to form a finite-dimensional state-space model. Spatial frequency analysis methods are introduced that systematically specify the basis function configuration required to capture the dominant characteristics of the neural field. The estimation procedure consists of a two-stage iterative algorithm incorporating the unscented Rauch–Tung–Striebel smoother for state estimation and a least squares algorithm for parameter estimation. The results show that it is theoretically possible to reconstruct the neural field and estimate intracortical connectivity structure and synaptic dynamics with the proposed framework

Late Byzantine Mineral Soda High Alumina Glasses from Asia Minor: A New Primary Glass Production Group

The chemical characterisation of archaeological glass allows the discrimination between different glass groups and the identification of raw materials and technological traditions of their production. Several lines of evidence point towards the large-scale production of first millennium CE glass in a limited number of glass making factories from a mixture of Egyptian mineral soda and a locally available silica source. Fundamental changes in the manufacturing processes occurred from the eight/ninth century CE onwards, when Egyptian mineral soda was gradually replaced by soda-rich plant ash in Egypt as well as the Islamic Middle East. In order to elucidate the supply and consumption of glass during this transitional period, 31 glass samples from the assemblage found at Pergamon (Turkey) that date to the fourth to fourteenth centuries CE were analysed by electron microprobe analysis (EPMA) and by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The statistical evaluation of the data revealed that the Byzantine glasses from Pergamon represent at least three different glass production technologies, one of which had not previously been recognised in the glass making traditions of the Mediterranean. While the chemical characteristics of the late antique and early medieval fragments confirm the current model of glass production and distribution at the time, the elemental make-up of the majority of the eighth- to fourteenth-century glasses from Pergamon indicate the existence of a late Byzantine glass type that is characterised by high alumina levels. Judging from the trace element patterns and elevated boron and lithium concentrations, these glasses were produced with a mineral soda different to the Egyptian natron from the Wadi Natrun, suggesting a possible regional Byzantine primary glass production in Asia Minor

Controlling for pleasure and risk: The experiences of sexuality and gender diverse people who use GHB

Background: GHB is used among some sexuality and gender diverse populations at elevated rates, however little qualitative research has explored GHB use among these populations with regards to diverse contexts, settings, practices, and experiences of use. Internationally, harms relating to GHB overdose appear to be increasing. Research outlining consumers’ experiences of GHB-related pleasures and their strategies to reduce harms may inform GHB education and intervention responses. Methods: N = 31 participants reporting three or more occasions of GHB use within the previous 12 months were recruited via digital advertising and snowball methods. Semi-structured interviews were conducted, data were transcribed and analysed in NVivo using a thematic framework analysis. Emergent themes were charted, and divergences and convergences were considered with regards to the sexuality and gender identities of participants. Results: Pleasures associated with GHB were described in relation to the sensation of the GHB high and experiences of intimacy, and connection. GHB was used to enhance socialising and sex in domestic, private, and commercial venues. Participants prioritised terminology of ‘control’ when describing their practices associated with GHB dosing, measuring, timing and peer moderation. Most participants reported personal experience of GHB overdose with loss of consciousness. Conclusion: Participants’ near-ubiquitous experience of GHB overdose highlights ongoing education needs around overdose prevention. Efforts must target people new to GHB use who appeared particularly susceptible to overdose. Inconsistencies in understandings around GHB overdose, the perceived severity of overdose and the differences between GHB and its precursors GBL and 1,4-BD, highlight potential focus areas of future education responses. Further research is required to better understand consumers’ experiences of sexual violence in the context of GHB use

Extremism and common mental illness: cross-sectional community survey of White British and Pakistani men and women living in England.

BACKGROUND: Mental illnesses may explain vulnerability to develop extremist beliefs that can lead to violent protest and terrorism. Yet there is little evidence.AimsTo investigate the relationship between mental illnesses and extremist beliefs. METHOD: Population survey of 618 White British and Pakistani people in England. Extremism was assessed by an established measure of sympathies for violent protest and terrorism (SVPT). Respondents with any positive scores (showing sympathies) were compared with those with all negative scores. We calculated associations between extremist sympathies and ICD-10 diagnoses of depression and dysthymia, and symptoms of anxiety, personality difficulties, autism and post-traumatic stress. Also considered were demographics, life events, social assets, political engagement and criminal convictions. RESULTS: SVPT were more common in those with major depression with dysthymia (risk ratio 4.07, 95% CI 1.37-12.05, P = 0.01), symptoms of anxiety (risk ratio 1.09, 95% CI 1.03-1.15, P = 0.002) or post-traumatic stress (risk ratio 1.03, 95% CI 1.01-1.05, P = 0.003). At greater risk of SVPT were: young adults (&lt;21 versus ≥21: risk ratio 3.05, 95% CI 1.31-7.06, P = 0.01), White British people (versus Pakistani people: risk ratio 2.24, 95% CI 1.25-4.02, P = 0.007) and those with criminal convictions (risk ratio 2.23, 95% CI 1.01-4.95, P = 0.048). No associations were found with life events, social assets and political engagement. CONCLUSION: Depression, dysthymia and symptoms of anxiety and post-traumatic stress are associated with extremist sympathies.Declaration of interestK.B. is editor-in-chief of British Journal of Psychiatry but played no part in review and decision processes.National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care North Thames at Bart's Health NHS Trust (NIHR CLAHRC North Thame

Дослідження «великого терору» у науково-документальній серії книг «Реабілітовані історією»

У статті автор аналізує результати дослідження «великого терору» 1937–1938 рр. у контексті реалізації Державної програми науково-документальної серії книг «Реабілітовані історією».В статье автор анализирует результаты исследования «большого террора» 1937–1938 гг. в контексте реализации Государственной программы научно-документальной серии книг «Реабилитированные историей».The author analyzes the results of a study of the «great terror» 1937–1938 in the context of implementing the State Program for Research, a documentary series of books «Rehabilitated history»

Composition of Byzantine glasses from Umm el-Jimal, northeast Jordan: Insights into glass origins and recycling

Twenty glass samples collected from four structures at Umm el-Jimal, northeast Jordan were analysed using the Electron Probe Micro-Analysis (EPMA). Except one ash-soda-lime-silica glass, all were natron-soda-lime-silica glasses of Levantine origin. Most of the glasses compositionally resemble glass from the Byzantine tank furnaces at Apollonia-Arsuf (Arsuf), but four with lower lime are closer to Umayyad period production at Bet Eli’ezer (Hadera). The paper presents diagnostic information indicating recycling in a Diagnostic Recycling Table (DRT) in which the analyses are ranked in a descending order of K2O, a key contaminant in the recycling process. This allows the comparison of a range of contaminant elements and it is observed that in general glass contaminated with fuel ash components K2O, P2O5 and CaO are also richer in transition metal oxides CuO, PbO, FeO and MnO, confirming that both sets of elements are important in identifying recycled glass. Chlorine is also identified as a component modified by recycling. The results ascertain that Umm el-Jimal was part of a major system of glass recycling in the Byzantine period, and emphasise the importance of recycled glass in its supply, in spite of its relative proximity to the location of raw glass production on the Syro-Palestinian coast