The First Episode Rapid Early Intervention for Eating Disorders - Upscaled study: Clinical outcomes.

BACKGROUND: First Episode Rapid Early Intervention for Eating Disorders (FREED) is a service model and care pathway for emerging adults aged 16 to 25-years with a recent onset eating disorder (ED) of <3 years. A previous single-site study suggests that FREED significantly improves clinical outcomes compared to treatment-as-usual (TAU). The present study (FREED-Up) assessed the scalability of FREED. A multi-centre quasi-experimental pre-post design was used, comparing patient outcomes before and after implementation of FREED in participating services. METHODS: FREED patients (n = 278) were consecutive, prospectively ascertained referrals to four specialist ED services in England, assessed at four time points over 12 months on ED symptoms, mood, service utilization and cost. FREED patients were compared to a TAU cohort (n = 224) of similar patients, identified retrospectively from electronic patient records in participating services. All were emerging adults aged 16-25 experiencing a first episode ED of <3 years duration. RESULTS: Overall, FREED patients made significant and rapid clinical improvements over time. 53.2% of FREED patients with anorexia nervosa reached a healthy weight at the 12-month timepoint, compared to only 17.9% of TAU patients (X2 [1, N = 107] = 10.46, p < .001). Significantly fewer FREED patients required intensive (i.e., in-patient or day-patient) treatment (6.6%) compared to TAU patients (12.4%) across the follow-up period (X2 [1, N = 40] = 4.36, p = .037). This contributed to a trend in cost savings in FREED compared to TAU (-£4472, p = .06, CI -£9168, £233). DISCUSSION: FREED is robust and scalable and is associated with substantial improvements in clinical outcomes, reduction in inpatient or day-patient admissions, and cost-savings.

Anti-centrosome antibodies in breast cancer are the expression of autoimmunity.

Centrosome abnormalities have been observed in nearly all human solid tumors, but their role in tumorigenesis is unclear. We have demonstrated that autoantibodies reacting with antigens in centrosomes are frequently found in BC sera. In this work, we attempted to characterize the centrosome antigens associated with BC. We immunoscreened a T7 cDNA library of BC proteins with BC sera, and the autoantigens identified were printed as a microarray and hybridized with BC and control sera. We used immunohistochemistry (IHC) to investigate the expression of the cloned autoantigens in BC tissue. Immunoscreening with BC sera led to the cloning of autoantibodies recognizing epitopes developing in a family of proteins located on centrosomes such as peri-centriolar material-1, isomorph CRA, stathmin1, HS actin gamma1, SUMO/sentrin peptidase 2, and ubiquitin-conjugating enzyme E2 variant 1. Antibody reactivity to these proteins that are associated with centrosome assembly and/or microtubule function was highly associated with the diagnosis of BC. IHC staining of formalin-fixed paraffin-embedded sections with specific antibodies showed that aurora and stathmin are expressed in BC. The discovery of autoantibodies to important centrosome antigens associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our finding that some of these antibodies are also present in a group of healthy women suggests that breakdown of tolerance to centrosome proteins may occur early in breast carcinogenesis and that autoantibodies to centrosome antigens might be biomarkers of early BC.

A practical discussion of risk management for manufacturing of pharmaceutical products.

Quality risk management (QRM) is now a regulatory expectation, and it makes good business sense. The goal of the risk assessment is to increase process understanding and deliver safe and effective product to the patients. Risk analysis and management is an acceptable and effective way to minimize patient risk and determine the appropriate level of controls in manufacturing. While understanding the elements of QRM is important, knowing how to apply them in the manufacturing environment is essential for effective process performance and control. This article will preview application of QRM in pharmaceutical and biopharmaceutical manufacturing to illustrate how QRM can help the reader achieve that objective. There are several areas of risk that a drug company may encounter in pharmaceutical manufacturing, specifically addressing oral solid and liquid formulations. QRM tools can be used effectively to identify the risks and develop strategy to minimize or control them. Risks are associated throughout the biopharmaceutical manufacturing process-from raw material supply through manufacturing and filling operations to final distribution via a controlled cold chain process. Assessing relevant attributes and risks for biotechnology-derived products is more complicated and challenging for complex pharmaceuticals. This paper discusses key risk factors in biopharmaceutical manufacturing. LAY ABSTRACT: Successful development and commercialization of pharmaceutical products is all about managing risks. If a company was to take zero risk, most likely the path to commercialization would not be commercially viable. On the other hand, if the risk taken was too much, the product is likely to have a suboptimal safety and efficacy profile and thus is unlikely to be a successful product. This article addresses the topic of quality risk management with the key objective of minimizing patient risk while creating an optimal process and product. Various tools are presented to aid implementation of these concepts.

Binocular summation of second-order global motion signals in human vision.

Although many studies have examined the principles governing first-order global motion perception, the mechanisms that mediate second-order global motion perception remain unresolved. This study investigated the existence, nature and extent of the binocular advantage for encoding second-order (contrast-defined) global motion. Motion coherence thresholds (79.4% correct) were assessed for determining the direction of radial, rotational and translational second-order motion trajectories as a function of local element modulation depth (contrast) under monocular and binocular viewing conditions. We found a binocular advantage for second-order global motion processing for all motion types. This advantage was mainly one of enhanced modulation sensitivity, rather than of motion-integration. However, compared to findings for first-order motion where the binocular advantage was in the region of a factor of around 1.7 (Hess et al., 2007), the binocular advantage for second-order global motion was marginal, being in the region of around 1.2. This weak enhancement in sensitivity with binocular viewing is considerably less than would be predicted by conventional models of either probability summation or neural summation.

Visual discrimination in noise: behavioural correlates of age-related cortical decline.

Neurophysiological evidence has consistently shown that, compared to younger animals, single neurons in aged mammalian visual cortex exhibit reduced selectivity to stimulus direction and orientation. It has been suggested that this may be due, in part, to increased internal noise in the aged visual system. This study measured contrast thresholds for judging the motion direction (left vs. right) and spatial orientation (vertical vs. horizontal) of sinusoidal gratings presented alone and with additive noise in young (20-29 years) and older (65-79 years) adults. Compared to their young counterparts, older adults demonstrated reduced sensitivity to direction and orientation when no noise was present. However, when gratings were presented in conjunction with additive noise, older adults required a greater increase in external noise to elicit a corresponding reduction in sensitivity. Subsequent analysis assessing equivalent noise and sampling efficiency attributed performance differences to an increase in equivalent noise with age.