A new mathematical model for the homeostatic effects of sleep loss on neurobehavioral performance

The two-process model of sleep regulation makes accurate predictions of sleep timing and duration for a variety of experimental sleep deprivation and nap sleep scenarios. Upon extending its application to waking neurobehavioral performance, however, the model fails to predict the effects of chronic sleep restriction. Here we show that the two-process model belongs to a broader class of models formulated in terms of coupled non-homogeneous first-order ordinary differential equations, which have a dynamic repertoire capturing waking neurobehavioral functions across a wide range of wake/sleep schedules. We examine a specific case of this new model class, and demonstrate the existence of a bifurcation: for daily amounts of wakefulness less than a critical threshold, neurobehavioral performance is predicted to converge to an asymptotically stable state of equilibrium; whereas for daily wakefulness extended beyond the critical threshold, neurobehavioral performance is predicted to diverge from an unstable state of equilibrium. Comparison of model simulations to laboratory observations of lapses of attention on a psychomotor vigilance test (PVT), in experiments on the effects of chronic sleep restriction and acute total sleep deprivation, suggests that this bifurcation is an essential feature of performance impairment due to sleep loss. We present three new predictions that may be experimentally verified to validate the model. These predictions, if confirmed, challenge conventional notions about the effects of sleep and sleep loss on neurobehavioral performance. The new model class implicates a biological system analogous to two connected compartments containing interacting compounds with time-varying concentrations as being a key mechanism for the regulation of psychomotor vigilance as a function of sleep loss. We suggest that the adenosinergic neuromodulator/receptor system may provide the underlying neurobiology.     

Carotid artery stenting: a single center "real world" experience

Background

Percutaneous carotid artery stenting (CAS) became a widely used procedure in patients with symptomatic and asymptomatic carotid artery stenosis. However its role compared to carotid endarterectomy (CAD) remains questioned. We analysed the safety of carotid artery stenting program of a prospective CAS register program of a tertiary teaching hospital.

Method

Between July 2003 and December 2010, 208 patients underwent CAS procedure. Baseline, procedural and follow-up data were prospectively collected. Primary peri-interventional outcome was defined as 30-day major adverse events (MAE), including death, stroke or myocardial infarction, and mid- to long-term follow-up outcome included ipsilateral stroke, myocardial infarction or death. Secondary outcome was restenosis rate ≥50% per lesion.

Results

Unilateral carotid artery interventions were performed in 186 patients. In 22 patients CAS was performed bilaterally as stages procedures. The 30-day MAE rate was 1.9% consisting of two contralateral strokes and two ipsilateral stroke. Mean clinically follow-up was 22 months. Mid- to long-term MAE was 8.1% with 6.3% (n = 13) deaths, 1.9% (n = 4) myocardial infarctions and 0.9% (n = 2) ipsilateral stroke. The restenosis rate ≥50% per lesion was 4.3% at a mean follow-up of 22 months. Target lesion revascularization was performed in one patient, because of restenosis at 9 months follow-up after first CAS.

Conclusion

Implementation of a carotid artery stenting program at a tertiary, teaching hospital is a safe method for treatment of carotid artery stenosis. The adverse event rate during mid-to-long-term follow-up suggests an appropriate patient selection.     

Malaria parasites in mosquitoes: laboratory models, evolutionary temptation and the real world

A recent study describing the effect of Plasmodium berghei infection on some Anopheles gambiae immune genes demonstrates that P. berghei is responsible for the upregulation of several genes involved in the immune response that affect parasitic development differently during the ookinete-to-oocyst developmental transition. It is important to question the relevance of such results, which are based on a laboratory model system, when discussing host-parasite interactions and, especially, the development of novel control strategies for malaria.     

Circadian biology: clocks for the real world.

The circadian system of Neurospora crassa includes a molecular feedback loop that is entrainable by light. A recent study has shown that a second, elusive oscillator interacts with the feedback loop to drive output rhythms.     

Commentary: future considerations for models of human neurobehavioral function

Modeling human neurobehavioral functions has the goal of identifying work-rest schedules that are safer and more productive. The models of Folkard et al. and of Jewett and Kronauer illustrate excellent progress toward this goal. Examination of these models reveals four additional areas that need to be addressed to facilitate continued development of accurate models of neurobehavioral functions. (1) The choice of neurobehavioral metrics may have a significant influence on model development. The lack of correlation among different neurobehavioral measures may make comparisons of models difficult. Many neurobehavioral measures are confounded by secondary and random error variance that can lead to model distortion. Although different models may ultimately be required for different neurobehavioral functions, measures that have been extensively validated to be sensitive to circadian variation and sleep loss should take priority in model development. (2) Because error variance in neurobehavioral outcomes can be substantial in uncontrolled environments, model validation should proceed from controlled laboratory protocols to real-world scenarios. Once validated, the ability of a model to predict field data can be tested. (3) While neurobehavioral models have been developed to predict behavior over time (i.e., within-subjects), to be useful in the real world, models will also ultimately have to provide estimates of between-subject variation in vulnerability to neurobehavioral dysfunction during night work or sleep loss (e.g., younger versus older workers). (4) Finally, to be theoretically accurate and practically useful, models of human neurobehavioral functions should be able to predict both cumulative effects (i.e., across days or weeks) and the influence of countermeasures (e.g., light, naps, caffeine).     

Model phylogenies to explain the real world

Phylogenetic trees based on gene sequence data contain information about the evolutionary processes responsible for their genesis. Methods have now been developed which help to reveal those processes. The methods are based on simple models of evolutionary change but, when applied across individuals in a population, rather than across species in a higher-level taxon, they can reveal the past history of population change. Examples from salamanders and viruses are used to illustrate how the past history of changes in speciation rate and the origin of epidemics can be inferred in the absence of fossil material or historical documentation.     

Bringing the real world into the biology curriculum

This study followed a small but diverse group of biology teachers through the first two years of the pilot for a new Advanced Level Biology course - Salters-Nuffield Advanced Biology. SNAB aims to modernise A-level Biology using real world contexts and examples as the starting point, promoting conceptual understanding rather than factual recall, encouraging active learning and developing a capacity for critical thinking and reflection. If the teachers were to implement this new curriculum as intended they would have to change some of their usual practices. The challenges which they encountered and the ways in which they responded were identified through a series of semi-structured interviews with each teacher, supported by lesson observations and interviews with students and technicians. A major constraint on changing practice was uncertainty about how to manage new approaches effectively.     

Critical evaluation of mathematical models for the amplification of chirality

The main types of models related to the origin of biological asymmetry are reviewed and new models are proposed. It is shown that in polymerization (in contrast to Yamagata's hypothesis) only a temporary amplification of asymmetry occurs. Models have been constructed in which always the same enantiomer survives, independently of any fluctuations or asymmetric initial conditions. Therefore, the question of the by chance or the causal origin of biological asymmetry remains still open, although with a slight preference for a causal origin.     

Scale and conservation planning in the real world

Conservation planning is carried out on a variety of geopolitical and biogeographical scales. Whereas considerable consensus is emerging about the most appropriate procedures for identifying conservation areas, the spatial implications of conducting conservation planning at divergent scales have received little attention. Here we explore the consequences of planning at different geopolitical scales, using a database of the mammalian fauna from the Northern Provinces of South Africa. The conservation network resulting from treating the region as one unit is compared with networks generated separately for the provinces nested in that region. These outcomes are evaluated in terms of (i) their land use efficiencies, (ii) their spatial overlap, and (iii) the impact of algorithm attributes. Although land use efficiencies are greater on broader scales, on average the spatial congruence between the broad-scale regional network and fine-scale provincial networks was less than 14%. Algorithms using different selection rules fail to improve this disturbing outcome. Consequently, scale has an overwhelming influence on areas identified as conservation networks in geopolitical units. This should be recognized in conservation planning.     

Integrated mathematical models for describing complex biological processes

This review describes integrated mathematical models of processes, such as calcium homeostasis, pathogen–host interaction (with hepatitis C virus as a pathogen), and the response of the human brain to a stimulating event. It is shown that integrated mathematical models provide a deeper insight into the mechanisms and conditions that lead to the development of diseases of different natures (musculoskeletal disorders, viral infections, and various impairments in brain function) and aid identification of the key targets and conditions for a directed effect of new generation drugs, as well as the interpretation of the results of state-of-theart CT imaging.