Inflammatory biomarkers in Alzheimer's disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

Wide Variation in the Use of Radiotherapy in the Management of Surgically Treated Rectal Cancer Across the English National Health Service

Aims: Radiotherapy is an important treatment modality in the multidisciplinary management of rectal cancer. It is delivered both in the neoadjuvant setting and postoperatively, but, although it reduces local recurrence, it does not influence overall survival and increases the risk of long-term complications. This has led to a variety of international practice patterns. These variations can have a significant effect on commissioning, but also future clinical research. This study explores its use within the large English National Health Service (NHS). Materials and methods: Information on all individuals diagnosed with a surgically treated rectal cancer between April 2009 and December 2010 were extracted from the Radiotherapy Dataset linked to the National Cancer Data Repository. Individuals were grouped into those receiving no radiotherapy, short-course radiotherapy with immediate surgery (SCRT-I), short-course radiotherapy with delayed surgery (SCRT-D), long-course chemoradiotherapy (LCCRT), other radiotherapy (ORT) and postoperative radiotherapy (PORT). Patterns of use were then investigated. Results: The study consisted of 9201 individuals; 4585 (49.3%) received some form of radiotherapy. SCRT-I was used in 12.1%, SCRT-D in 1.2%, LCCRT in 29.5%, ORT in 4.7% and PORT in 2.3%. Radiotherapy was used more commonly in men and in those receiving an abdominoperineal excision and less commonly in the elderly and those with comorbidity. Significant and substantial variations were also seen in its use across all the multidisciplinary teams managing this disease. Conclusion: Despite the same evidence base, wide variation exists in both the use of and type of radiotherapy delivered in the management of rectal cancer across the English NHS. Prospective population-based collection of local recurrence and patient-reported early and late toxicity information is required to further improve patient selection for preoperative radiotherapy

Developing our understanding of the language of extremism and its potential for predicting risk

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Developing our understanding of the language of extremism and its potential for predicting risk

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Adults with late diagnosed PKU and severe challenging behaviour: a randomised placebo-controlled trial of phenylolanine-restricted diet.

BACKGROUND: Although early diagnosis and treatment in phenylketonuria (PKU) leads to excellent outcomes, a population of adults born before the introduction of newborn screening exists. They can have severe intellectual disabilities and behavioural problems, and are often dependent on full-time carers. Anecdotal evidence suggests that a diet that lowers blood phenylalanine concentration can have significant benefits upon behaviour. METHODS: A prospective double-blind randomised placebo-controlled crossover trial of phenylalanine-restricted diet was performed in a group of 34 adults (aged 21-61 years, median 49) with late diagnosed PKU with severe challenging behaviour. RESULTS: Only 17 completed the 60 week study: seven withdrew before the end of the baseline period; five withdrew during the first diet period; five withdrew during the second diet period (after moving into placebo phase). The mean (SD) blood phenylalanine was 1570 (222) micromol/l during baseline, 553(158) mumol/l during the active phase and 1444 (255) micromol/l during the placebo phase. In the 22 participants exposed to both active and placebo phases, no differences were demonstrated in behaviour assessed by the Aberrant Behavior Checklist and Vineland Adaptive Behavior Scales, behaviour diaries or on video analysis of direct observations. However, 76% of carers' comments were scored as positive during the active phase, compared with 54% during the placebo phase (chi(2) = 38.06, p<0.001). CONCLUSIONS: There are significant challenges in studying people with intellectual disabilities and considerable difficulties in instituting phenylalanine-restricted diet in this population. However, if attempted, there are potential benefits to quality of life for the individuals with PKU and their carers

Quantification of condition monitoring benefit for offshore wind turbines

Condition monitoring (CM) systems are increasingly installed in wind turbines with the goal of providing component-specific information to wind farm operators, theoretically increasing equipment availability via maintenance and operating actions based on this information. In the offshore case, economic benefits of CM systems are often assumed to be substantial, as compared with experience of onshore systems. Quantifying this economic benefit is non-trivial, especially considering the general lack of utility experience with large offshore wind farms. A quantitative measure of these benefits is therefore of value to utilities and operations and maintenance (O & M) groups involved in planning and operating future offshore wind farms. The probabilistic models presented in this paper employ a variety of methods including discrete-time Markov Chains, Monte Carlo methods and time series modelling. The flexibility and insight provided by this framework captures the necessary operational nuances of this complex problem, thus enabling evaluation of wind turbine CM offshore. The paper concludes with a study of baseline CM benefit, sensitivity to O & M costs and finally effectiveness of the CM system itself