Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach

The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders.

Pilot study on the comprehensive economic costs of major trauma: Consequential costs are well in excess of medical costs

BACKGROUND: Trauma care is expensive. However, reliable data on the exact lifelong costs incurred by a major trauma patient are lacking. Discussion usually focuses on direct medical costs--underestimating consequential costs resulting from absence from work and permanent disability. METHODS: Direct medical costs and consequential costs of 63 major trauma survivors (ISS >13) at a Swiss trauma center from 1995 to 1996 were assessed 5 years posttrauma. The following cost evaluation methods were used: correction cost method (direct cost of restoring an original state), human capital method (indirect cost of lost productivity), contingent valuation method (human cost as the lost quality of life), and macroeconomic estimates. RESULTS: Mean ISS (Injury Severity Score) was 26.8 +/- 9.5 (mean +/- SD). In all, 22 patients (35%) were disabled, causing discounted average lifelong total costs of USD 1,293,800, compared with 41 patients (65%) who recovered without any disabilities with incurred costs of USD 147,200 (average of both groups USD 547,800). Two thirds of these costs were attributable to a loss of production whereas only one third was a result of the cost of correction. Primary hospital treatment (USD 27,800 +/- 37,800) was only a minor fraction of the total cost--less than the estimated cost of police and the judiciary. Loss of quality of life led to considerable intangible human costs similar to real costs. CONCLUSIONS: Trauma costs are commonly underestimated. Direct medical costs make up only a small part of the total costs. Consequential costs, such as lost productivity, are well in excess of the usual medical costs. Mere cost averages give a false estimate of the costs incurred by patients with/without disabilities.

More than a surprise: The bivalency effect in task switching

When switching tasks, if stimuli are presented that contain features that cue two of the tasks in the set (i.e., bivalent stimuli), performance slowing is observed on all tasks. This generalized slowing extends to tasks in the set which have no features in common with the bivalent stimulus and is referred to as the bivalency effect. In previous work, the bivalency effect was invoked by presenting occasionally occurring bivalent stimuli; therefore, the possibility that the generalized slowing is simply due to surprise (as opposed to bivalency) has not yet been discounted. This question was addressed in two task switching experiments where the occasionally occurring stimuli were either bivalent (bivalent version) or merely surprising (surprising version). The results confirmed that the generalized slowing was much greater in the bivalent version of both experiments, demonstrating that the magnitude of this effect is greater than can be accounted for by simple surprise. This set of results confirms that slowing task execution when encountering bivalent stimuli may be fundamental for efficient task switching, as adaptive tuning of response style may serve to prepare the cognitive system for possible future high conflict trials.

Static replications with traffic light options

It is well known that sufficiently regular, one-dimensional payoff functions have an explicit static hedge by bonds, forward contracts, and options in a continuum of strikes. An easy and natural extension of the corresponding representation leads to static hedges based on the same instruments along with traffic light options, which have recently been introduced in the market. It is well known that the second strike derivative of non-discounted prices of vanilla options is related to the risk-neutral density of the underlying asset price in the corresponding absolutely continuous settings. Similar statements hold for traffic light options in sufficiently regular, bivariate settings.

Ancient History as a Means of Transforming Colonial India in the Late-Eighteenth and Early-Nineteenth Centuries

This article focuses on the studies and discourses of mostly British scholars of the early colonial period belonging to two schools of thought. It shows how the studies of both schools – European orientalism and utilitarianism – were intricately connected to the political development of the emerging British paramountcy over the South Asian sub-continent, as both were looking for means of establishing and/or strengthening colonial rule. Nevertheless, the debate was not just a continuation of discussions in Europe. Whereas the ideas of the European Enlightenment had some influence, the transformation of the Mughal Empire and especially the idea of a decline of Muslim rule offered ample opportunities for understanding the early history of India either as some sort of “Golden Age,” as the orientalists and their indigenous supporters did, or as something static and degenerate, as the utilitarians did, and from which the population of sub-continent had to be saved by colonial rule and colonial values. Fearing the spread of the ideas of the French Revolution, the first group of British scholars sought to persuade the native elites of South Asia to take the lessons of their past for the future development of their homeland. Just as the classicists back in Europe, these scholars were convinced that large-scale explanations of the past could also teach political and moral lessons for the present although it was important to deal with the distant past in an empirical manner. The utilitarians on the other hand believed that India had to be saved from its own depravity through the English language and Western values, which amounted to nothing less than the modern transformation of the true Classical Age.

Zum Einfluss vorschulischer Kinderbetreuung auf den Bildungsweg und den erwarteten Erfolg am Arbeitsmarkt

In dem Beitrag wird der Frage nachgegangen, welchen Einfluss die Inanspruchnahme frühkindlicher Bildungs- und Betreuungsangebote auf den späteren Schulbesuch von Kindern hat und wie sich dies längerfristig auf die zu erwartenden Lebenseinkommen und damit einhergehend den langfristigen volkswirtschaftlichen Nutzen auswirkt. Untersucht werden Kinder in Deutschland der Jahrgänge 1990 bis 1995. Die Datengrundlage liefert das Sozio-oekonomische Panel (SOEP). Der Schwerpunkt der Analysen liegt auf der Bestimmung des Effekts des Krippenbesuchs auf die spätere Einstufung in die verschiedenen Schultypen in Abhängigkeit der sozialen Herkunft und des Migrationshintergrunds der Kinder. Ausgehend von diesen Schätzungen werden dann die zu erwartenden, über den Bildungsabschluss vermittelten Auswirkungen des Krippenbesuchs auf das spätere Lebenseinkommen bestimmt, um einen Eindruck der langfristigen volkswirtschaftlichen Folgen vorschulischer Kinderbetreuung zu erhalten. Der Beitrag zeigt, dass der Krippenbesuch die Wahrscheinlichkeit einer Einstufung ins Gymnasium nach Kontrolle relevanter Drittvariablen im Schnitt um rund 14 Prozentpunkte erhöht. Dieser Einfluss entspricht einem erwarteten Lebenseinkommenszuwachs von rund 27000 Euro. Wird dieser Ertrag auf den Zeitpunkt des Krippenbesuchs abdiskontiert und den Kosten eines durchschnittlichen Krippenbesuchs in der Höhe von rund 8000 Euro gegenübergestellt, so ergibt sich ein Kosten-Nutzen-Verhältnis von 1 zu 2.7. (DIPF/Orig.).