How reliable are self-report measures of mileage, violations and crashes?

The use of self-reported driver mileage, violations and crashes is very popular in traffic safety research, but their validity has been questioned. One way of testing validity is with an analysis of test–retest reliability. Three mechanisms might influence reliability in self report; actual changes in the variable over time, stable systematic reporting bias, and random error. Four samples of drivers who had responded twice to an online questionnaire asking them to report their mileage, violations and crashes were used and correlations between self reports for this data were calculated. The results for crashes were compared to expected correlations, calculated from the error introduced by the non-overlapping periods and the variable means. Reliability was fairly low, and controlling for mileage in the violations and crashes calculations did not strengthen the associations. The correlation between self reports of crashes in different time periods was found to be much larger than expected in one case, indicating a report bias, while the other correlation agreed with the predicted value. The correlations for overlapping time periods were much smaller than expected. These results indicate that drivers’ self reports about their mileage, violations and crashes are very unreliable, but also that several different mechanisms are operating. It is uncertain exactly under what circumstances different types of self report bias is operating. Traffic safety researchers should treat the use of self-reported mileage, violations and crashes with extreme caution and preferably investigate these variables with the use of objective data

Experience as a safety factor in driving; Methodological considerations in a sample of bus drivers

Experience is generally seen as an important factor for safe driving, but the exact size and details of this effect has never been meta-analytically described, despite a fair number of published results. However, the available data is heterogeneous concerning the methods used, which could lead to very different results. Such method effects can be difficult to identify in meta-analysis, and a within-study comparison might yield more reliable results. To test for the difference in effects between some different analytical methods, analyses of data on bus driver experience and crash involvement from a British company were conducted. Effects of within- and between-subjects analysis, non-linearity of effects, and direct and induced exposure methods were compared. Furthermore, changes in the environmental risk were investigated. Between-subject designs yielded smaller effects as compared to within-subjects designs, while non-linearity was not found. The type of exposure control applied had a strong influence on effects, as did differences in overall environmental risk between years. Apparently, “the effect of driving experience” means different things depending upon how calculations have been undertaken, at least for bus drivers. A full meta-analysis, taking several effects of methodology into account, is needed before it can be said that the effect of driving experience on crash involvement is well understood

Behavioural culpability for traffic accidents

This study presents a description of the concept of behavioural culpability, a step-by-step manual for using it, and an empirical test of a suspected mis-classification of culpability. Behavioural culpability is defined as whether the driver’s actions contributed to a crash and that non-culpable crashes are not caused by any specific behaviour and can only be predicted from exposure. Drivers with non-culpable crashes are therefore a random sample of the population. However, if the criteria for culpability and/or the individual judgements are not reflective of the principle of behavioural culpability, no fault drivers will not be a random sample of the driving population. To test the predictions from the definition of randomness in a sample assumed to have sub-optimal coding, the categorization of crash involvement undertaken by a British bus company was tested for associations between at fault and no fault crashes, age and experience. As predicted from the low percentage of at fault accidents in the sample, correlations between the variables indicated that a fair percentage of at fault crashes had been coded as no fault of the bus driver, suggesting a too lenient criterion. These results show that within fleet-based companies, culpability for a crash is probably allocated for legal reasons, which means that the predictability of accident involvement taking into account individual differences is not fully utilized. The aim of behavioural culpability coding is to increase effect sizes in individual differences in safety research and to improve our capability of predicting accident involvement

Bus driver accident record; stability over time, exposure and culpability

The tendency for drivers to have a stable accident record over time was tested in a population of bus drivers. Analyses included investigations of the effects of responsibility for the crash, exposure and length of time period, on stability. All associations between numbers of accidents for individuals in different short time periods were found to be weak, but longer time periods increased the size of the correlations. Restricting the analyses to include only those crashes for which the drivers were deemed responsible had a slightly negative effect on correlations. However, this was due to lower means (and thus variance) in these calculations. Similarly, controlling for hours worked decreased the correlations somewhat, but this was due to an outlier problem. The results are consistent with previous research and indicate that stability of accident involvement exists and that the effects can be reliably found under certain methodological circumstances. The sizes of coefficients are determined mainly by the restriction of variance, not by any underlying lack of stability. The stable tendency to cause mishaps within the same environment is a strong factor in traffic safety although this is not apparent when variance in the data is low

Accident proneness of bus drivers; controlling for exposure

It is argued that the reason that previous evidence apparently did not support the accident proneness hypothesis was faulty methodology and erroneous interpretations of results. Between time periods correlations of traffic accident records actually show an impressive stability over time when restriction of variance is controlled for. However, stability can be caused by stable differences in exposure. Correlations of accident records between time periods were analysed comparing full time and part-time bus drivers. For drivers who worked full time, the amount of exposure was held semi-constant while part-time drivers could be expected to work differing hours. If differential exposure causes stability in crash record, then part-time drivers should yield stronger correlations between time periods for crashes compared with full-time drivers. Between time periods accident correlations for part-time drivers were weaker than the corresponding ones for full time drivers. Correlations increased with increasing variance in the data. Results for all crashes fit in well with other meta-data, while culpable crashes did not, probably due to faulty coding. The current results support the notion of the tendency to cause traffic accidents as a stable trait within individuals as this is apparently not caused by stable differences in exposure

Correcting Glucose-6-Phosphate Dehydrogenase Deficiency with a Small-Molecule Activator

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the Canton mutant and several other common G6PD mutants. AG1 reduces oxidative stress in cells and zebrafish. Furthermore, AG1 decreases chloroquine- or diamide-induced oxidative stress in human erythrocytes. Our study suggests that a pharmacological agent, of which AG1 may be a lead, will likely alleviate the challenges associated with G6PD deficiency

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind

PurposeRetinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation.DesignThe study is a multicenter, single-arm, prospective clinical trial.ParticipantsThere were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision).MethodsThe Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina.Main Outcome MeasuresThe primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests.ResultsA total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments.ConclusionsThe 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals

Monoamine oxidase-dependent endoplasmic reticulum-mitochondria dysfunction and mast cell degranulation lead to adverse cardiac remodeling in diabetes.

Monoamine oxidase (MAO) inhibitors ameliorate contractile function in diabetic animals, but the mechanisms remain unknown. Equally elusive is the interplay between the cardiomyocyte alterations induced by hyperglycemia and the accompanying inflammation. Here we show that exposure of primary cardiomyocytes to high glucose and pro-inflammatory stimuli leads to MAO-dependent increase in reactive oxygen species that causes permeability transition pore opening and mitochondrial dysfunction. These events occur upstream of endoplasmic reticulum (ER) stress and are abolished by the MAO inhibitor pargyline, highlighting the role of these flavoenzymes in the ER/mitochondria cross-talk. In vivo, streptozotocin administration to mice induced oxidative changes and ER stress in the heart, events that were abolished by pargyline. Moreover, MAO inhibition prevented both mast cell degranulation and altered collagen deposition, thereby normalizing diastolic function. Taken together, these results elucidate the mechanisms underlying MAO-induced damage in diabetic cardiomyopathy and provide novel evidence for the role of MAOs in inflammation and inter-organelle communication. MAO inhibitors may be considered as a therapeutic option for diabetic complications as well as for other disorders in which mast cell degranulation is a dominant phenomenon

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure