A Bayesian Filtering Algorithm for Gaussian Mixture Models

A Bayesian filtering algorithm is developed for a class of state-space systems that can be modelled via Gaussian mixtures. In general, the exact solution to this filtering problem involves an exponential growth in the number of mixture terms and this is handled here by utilising a Gaussian mixture reduction step after both the time and measurement updates. In addition, a square-root implementation of the unified algorithm is presented and this algorithm is profiled on several simulated systems. This includes the state estimation for two non-linear systems that are strictly outside the class considered in this paper

An Independent Audit of Pharma Influence in Public Mental Health Trusts in England

Without data, many people still think pharmaceutical companies’ influence is negligible, even benevolent. We audited their marketing activities, alongside simple financials. 43/53 Trusts responded to Freedom-of-Information-Act requests. Trusts’ policies varied in prohibiting seven activities: 86% (gifts) to 37% (leaflets). In practice, industry-sponsored training events (51%)/ direct talks (40%) were common (averaging 36 sponsored events/talks per Trust that year). Only 8/36 (22.2%) Trusts provided legally-required Conflicts-of-Interests registers; 5 (14%) had none. The top training-provider/sponsor received almost double where they trained most, and the largest share (average 33.6%) of the whole psychiatric-medications budget everywhere. Two most expensive medications (branded, “Long-Acting-Injectables”) were prescribed very differently (0%-77%). Independent post-qualification medical education/ marketing-bans are needed to avoid extremely over-medicalised practice. 5 Trusts already ban Pharma marketing

Toll-like Receptor-4 Regulation of Hepatic Cyp3a11 Metabolism in a Mouse Model of LPS-induced CNS Inflammation

Central nervous system (CNS) infection and inflammation severely reduce the capacity of cytochrome P-450 metabolism in the liver. We developed a mouse model to examine the effects of CNS inflammation on hepatic cytochrome P-450 metabolism. FVB, C57BL/6, and C3H/HeouJ mice were given Escherichia coli LPS (2.5 μg) by intracerebroventricular (ICV) injection. The CNS inflammatory response was confirmed by the elevation of TNF-α and/or IL-1β proteins in the brain. In all mouse strains, LPS produced a 60–70% loss in hepatic Cyp3a11 expression and activity compared with saline-injected controls. Adrenalectomy did not prevent the loss in Cyp3a11 expression or activity, thereby precluding the involvement of the hypothalamic-adrenal-pituitary axis. Endotoxin was detectable (1–10 ng/ml) in serum between 15 and 120 min after ICV dosing of 2.5 μg LPS. Peripheral administration of 2.5 μg LPS by intraperitoneal injection produced similar serum endotoxin levels and a similar loss (60%) in Cyp3a11 expression and activity in the liver. The loss of Cyp3a11 in response to centrally or peripherally administered LPS could not be evoked in Toll-like receptor-4 (TLR4)-mutant (C3H/ HeJ) mice, indicating that TLR4 signaling pathways are directly involved in the enzyme loss. In summary, we conclude that LPS is transferred from the brain to the circulation in significant quantities in a model of CNS infection or inflammation. Subsequently, LPS that has reached the circulation stimulates a TLR4-dependent mechanism in the periphery, evoking a reduction in Cyp3a11 expression and metabolism in the liver

Do English mental health services know whether they followed N.I.C.E. guidelines with patients who killed themselves?

Summary Freedom of Information Act requests sent to 51 NHS mental health providers in England showed an average of 20.5 suicides per organisation. Only one provider, however, could report how many people that had killed themselves had been offered N.I.C.E. recommended psychological therapy. Information that might prevent suicides is being ignored. Practitioner Points • Mental health services need, urgently, to develop data systems that can inform clinical team leaders about gaps in their services to suicidal people in their care • Clinical psychologists have a particular responsibility to pressure managers to effectively monitor the provision of evidence-based treatments to suicidal people • Trusts and commissioners must be aware of, and rectify, any failings of their services in relation to the prevention of suicide Ke