Historical overview of development in methods to estimate burden of disease due to congenital disorders.

Congenital disorders (often also called birth defects) are an important cause of mortality and disability. They encompass a wide range of disorders with differing severity that can affect any aspect of structure or function. Understanding their epidemiology is important in developing appropriate services both for their prevention and treatment. The need for epidemiological data on congenital disorders has been recognised for many decades. Here, we provide a historical overview of work that has led to the development of the Modell Global Database of Congenital Disorders (MGDb)-a tool that can be used to generate evidence-based country, regional and global estimates of the birth prevalence and outcomes of congenital disorders

The Influence of Fallback Foods on Great Ape Tooth Enamel

Lucas and colleagues recently proposed a model based on fracture and deformation concepts to describe how mammalian tooth enamel may be adapted to the mechanical demands of diet (Lucas et al.: Bioessays 30[2008] 374-385). Here we review the applicability of that model by examining existing data on the food mechanical properties and enamel morphology of great apes (Pan, Pongo, and Gorilla). Particular attention is paid to whether the consumption of fallback foods is likely to play a key role in influencing great ape enamel morphology. Our results suggest that this is indeed the case. We also consider the implications of this conclusion on the evolution of the dentition of extinct hominins

Fracture in teeth—a diagnostic for inferring bite force and tooth function

Teeth are brittle and highly susceptible to cracking. We propose that observations of such cracking can be used as a diagnostic tool for predicting bite force and inferring tooth function in living and fossil mammals. Laboratory tests on model tooth structures and extracted human teeth in simulated biting identify the principal fracture modes in enamel. Examination of museum specimens reveals the presence of similar fractures in a wide range of vertebrates, suggesting that cracks extended during ingestion or mastication. The use of ‘fracture mechanics’ from materials engineering provides elegant relations for quantifying critical bite forces in terms of characteristic tooth size and enamel thickness. The role of enamel microstructure in determining how cracks initiate and propagate within the enamel (and beyond) is discussed. The picture emerges of teeth as damage-tolerant structures, full of internal weaknesses and defects and yet able to contain the expansion of seemingly precarious cracks and fissures within the enamel shell. How the findings impact on dietary pressures forms an undercurrent of the study

Improved memory for information learnt before alcohol use in social drinkers tested in a naturalistic setting

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.Alcohol is known to facilitate memory if given after learning information in the laboratory; we aimed to investigate whether this effect can be found when alcohol is consumed in a naturalistic setting. Eighty-eight social drinkers were randomly allocated to either an alcohol self-dosing or a sober condition. The study assessed both retrograde facilitation and alcohol induced memory impairment using two independent tasks. In the retrograde task, participants learnt information in their own homes, and then consumed alcohol ad libitum. Participants then undertook an anterograde memory task, of alcohol impairment when intoxicated. Both memory tasks were completed again the following day. Mean amount of alcohol consumed was 82.59 grams over the evening. For the retrograde task, as predicted, both conditions exhibited similar performance on the memory task immediately following learning (before intoxication) yet performance was better when tested the morning after encoding in the alcohol condition only. The anterograde task did not reveal significant differences in memory performance post-drinking. Units of alcohol drunk were positively correlated with the amount of retrograde facilitation the following morning. These findings demonstrate the retrograde facilitation effect in a naturalistic setting, and found it to be related to the self-administered grams of alcohol.The study was funded by an MRC grant to CJAM (MR/L023032/1), we would like to thank all the participants for their time

Phase Transition in a Random Fragmentation Problem with Applications to Computer Science

We study a fragmentation problem where an initial object of size x is broken into m random pieces provided x>x_0 where x_0 is an atomic cut-off. Subsequently the fragmentation process continues for each of those daughter pieces whose sizes are bigger than x_0. The process stops when all the fragments have sizes smaller than x_0. We show that the fluctuation of the total number of splitting events, characterized by the variance, generically undergoes a nontrivial phase transition as one tunes the branching number m through a critical value m=m_c. For m<m_c, the fluctuations are Gaussian where as for m>m_c they are anomalously large and non-Gaussian. We apply this general result to analyze two different search algorithms in computer science.Comment: 5 pages RevTeX, 3 figures (.eps

The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for Cigarettes in Dependent and Occasional Cigarette Smokers

Background: Dopaminergic functioning is thought to play critical roles in both motivation and addiction. There is preliminary evidence that dopamine agonists reduce the motivation for cigarettes in smokers. However, the effects of pramipexole, a dopamine D3 receptor preferring agonist, have not been investigated. The aim of this study was to examine the effects of an acute dose of pramipexole on the motivation to earn cigarettes and nondrug rewards. Methods: Twenty dependent and 20 occasional smokers received 0.5 mg pramipexole using a double-blind, placebo-controlled crossover design. Motivation for cigarettes and consummatory nondrug rewards was measured using the DReaM-Choice task, in which participants earned, and later "consumed," cigarettes, music, and chocolate. Demand for cigarettes was measured using the Cigarette Purchase Task (CPT). Self-reported craving, withdrawal, and drug effects were also recorded. Results: Dependent smokers chose (p < .001) and button-pressed for (p < .001) cigarettes more, and chose chocolate less (p < .001), than occasional smokers. Pramipexole did not affect the number of choices for or amount of button-pressing for any reward including cigarettes, which was supported by a Bayesian analysis. The dependent smokers had greater demand for cigarettes than occasional smokers across all CPT outcomes (ps < .021), apart from elasticity. Pramipexole did not affect demand for cigarettes, and this was supported by Bayesian analyses. Pramipexole produced greater subjective "feel drug" and "dislike drug" effects than placebo. Conclusions: Dependent and occasional cigarette smokers differed in their motivation for cigarettes but not for the nondrug rewards. Pramipexole did not acutely alter motivation for cigarettes. These findings question the role of dopamine D3 receptors in cigarette-seeking behavior in dependent and occasional smokers. Implications: This study adds to the growing literature about cigarette versus nondrug reward processing in nicotine dependence and the role of dopamine in cigarette-seeking behavior. Our results suggest nicotine dependence is associated with a hypersensitivity to cigarette rewards but not a hyposensitivity to nondrug rewards. Furthermore, our results question the importance of dopamine D3 receptors in motivational processing of cigarettes in occasional and dependent smokers

Pattern formation and selection in quasi-static fracture

Fracture in quasi-statically driven systems is studied by means of a discrete spring-block model. Developed from close comparison with desiccation experiments, it describes crack formation induced by friction on a substrate. The model produces cellular, hierarchical patterns of cracks, characterized by a mean fragment size linear in the layer thickness, in agreement with experiments. The selection of a stationary fragment size is explained by exploiting the correlations prior to cracking. A scaling behavior associated with the thickness and substrate coupling, derived and confirmed by simulations, suggests why patterns have similar morphology despite their disparity in scales.Comment: 4 pages, RevTeX, two-column, 5 PS figures include

Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

Making stillbirths count, making numbers talk - issues in data collection for stillbirths.

BACKGROUND: Stillbirths need to count. They constitute the majority of the world's perinatal deaths and yet, they are largely invisible. Simply counting stillbirths is only the first step in analysis and prevention. From a public health perspective, there is a need for information on timing and circumstances of death, associated conditions and underlying causes, and availability and quality of care. This information will guide efforts to prevent stillbirths and improve quality of care. DISCUSSION: In this report, we assess how different definitions and limits in registration affect data capture, and we discuss the specific challenges of stillbirth registration, with emphasis on implementation. We identify what data need to be captured, we suggest a dataset to cover core needs in registration and analysis of the different categories of stillbirths with causes and quality indicators, and we illustrate the experience in stillbirth registration from different cultural settings. Finally, we point out gaps that need attention in the International Classification of Diseases and review the qualities of alternative systems that have been tested in low- and middle-income settings. SUMMARY: Obtaining high-quality data will require consistent definitions for stillbirths, systematic population-based registration, better tools for surveys and verbal autopsies, capacity building and training in procedures to identify causes of death, locally adapted quality indicators, improved classification systems, and effective registration and reporting systems

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses

Rationale: Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. Objectives: The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. Methods: In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. Results: Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). Conclusions: Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC