Evaluation of N (epsilon)-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy.

AIMS/HYPOTHESIS: Recent studies suggest that oxidative stress should be monitored alongside HbA(1c) to identify subgroups of diabetic patients at high risk of initiation or progression of retinopathy. The acrolein-derived advanced lipoxidation end-product (ALE), [Formula: see text]-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine), is a useful biomarker that reflects the cumulative burden of oxidative stress over long periods of time. The purpose of the present study was to investigate whether serum and haemoglobin levels of FDP-lysine are associated with the severity of diabetic retinopathy in type 1 and type 2 diabetic patients.

METHODS: Serum and haemoglobin levels of FDP-lysine were measured by competitive ELISA in 59 type 1 and 76 type 2 diabetic patients with no retinopathy, non-proliferative retinopathy or proliferative retinopathy (mean age [+/-SEM] 54.3 +/- 1.3 years), and in 47 non-diabetic control individuals (mean age 51.9 +/- 2.1 years).

RESULTS: Serum and haemoglobin levels of FDP-lysine were significantly increased in diabetic patients compared with control individuals (p = 0.04 and p = 0.002, respectively). However, no significant association was found between levels of serum FDP-lysine and the severity of diabetic retinopathy (p = 0.97). In contrast, increased haemoglobin FDP-lysine levels were observed in patients with proliferative retinopathy compared with patients without retinopathy and with non-proliferative retinopathy (p = 0.04). The relationship of FDP-lysine with proliferative retinopathy was unaltered after adjustment for HbA(1c), or other clinical parameters.

CONCLUSIONS/INTERPRETATION: Our data suggest that haemoglobin FDP-lysine may provide a useful risk marker for the development of proliferative diabetic retinopathy independently of HbA(1c), and that elevated intracellular ALE formation may be involved in the pathogenesis of this sight-threatening complication of diabetes.

Spatial attentional bias as a marker of genetic risk, symptom severity, and stimulant response in ADHD

Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (30 untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 30-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD.

Where there is smoke, there is (the potential for) fire: soft indicators of research and policy impact

There is a growing literature examining the impact of research on informing policy, and of research and policy on practice. Research and policy do not have the same types of impact on practice but can be evaluated using similar approaches. Sometimes the literature provides a platform for methodological debate but mostly it is concerned with how research can link to improvements in the process and outcomes of education, how it can promote innovative policies and practice, and how it may be successfully disseminated. Whether research-informed or research-based, policy and its implementation is often assessed on such 'hard' indicators of impact as changes in the number of students gaining five or more A to C grades in national examinations or a percentage fall in the number of exclusions in inner city schools. Such measures are necessarily crude, with large samples smoothing out errors and disguising instances of significant success or failure. Even when 'measurable' in such a fashion, however, the impact of any educational change or intervention may require a period of years to become observable. This paper considers circumstances in which short-term change may be implausible or difficult to observe. It explores how impact is currently theorized and researched and promotes the concept of 'soft' indicators of impact in circumstances in which the pursuit of conventional quantitative and qualitative evidence is rendered impractical within a reasonable cost and timeframe. Such indicators are characterized by their avowedly subjective, anecdotal and impressionistic provenance and have particular importance in the context of complex community education issues where the assessment of any impact often faces considerable problems of access. These indicators include the testimonies of those on whom the research intervention or policy focuses (for example, students, adult learners), the formative effects that are often reported (for example, by head teachers, community leaders) and media coverage. The collation and convergence of a wide variety of soft indicators (Where there is smoke …) is argued to offer a credible means of identifying subtle processes that are often neglected as evidence of potential and actual impact (… there is fire).