Choosing the number of doses and the cohort size for phase I dose-escalation studies

This paper reviews Bayesian procedures for phase 1 dose-escalation studies and compares different dose schedules and cohort sizes. The methodology described is motivated by the situation of phase 1 dose-escalation studiesin oncology, that is, a single dose administered to each patient, with a single binary response ("toxicity"' or "no toxicity") observed. It is likely that a wider range of applications of the methodology is possible. In this paper, results from 10000-fold simulation runs conducted using the software package Bayesian ADEPT are presented. Four designs were compared under six scenarios. The simulation results indicate that there are slight advantages of having more dose levels and smaller cohort sizes.

The severity of malarial anaemia in Plasmodium chabaudi infections of BALB/c mice is determined independently of the number of circulating parasites

Background: Severe malarial anaemia is a major complication of malaria infection and is multifactorial resulting from loss of circulating red blood cells (RBCs) from parasite replication, as well as immune-mediated mechanisms. An understanding of the causes of severe malarial anaemia is necessary to develop and implement new therapeutic strategies to tackle this syndrome of malaria infection. Methods: Using analysis of variance, this work investigated whether parasite-destruction of RBCs always accounts for the severity of malarial anaemia during infections of the rodent malaria model Plasmodium chabaudi in mice of a BALB/c background. Differences in anaemia between two different clones of P. chabaudi were also examined. Results: Circulating parasite numbers were not correlated with the severity of anaemia in either BALB/c mice or under more severe conditions of anaemia in BALB/c RAG2 deficient mice (lacking T and B cells). Mice infected with P. chabaudi clone CB suffered more severe anaemia than mice infected with clone AS, but this was not correlated with the number of parasites in the circulation. Instead, the peak percentage of parasitized RBCs was higher in CB-infected animals than in AS-infected animals, and was correlated with the severity of anaemia, suggesting that the availability of uninfected RBCs was impaired in CB-infected animals. Conclusion: This work shows that parasite numbers are a more relevant measure of parasite levels in P. chabaudi infection than % parasitaemia, a measure that does not take anaemia into account. The lack of correlation between parasite numbers and the drop in circulating RBCs in this experimental model of malaria support a role for the host response in the impairment or destruction of uninfected RBC in P. chabaudi infections, and thus development of acute anaemia in this malaria model.

Parents' cognitions and expectations about their pre-school children: the contribution of parental anxiety and child anxiety

This study investigated the relative associations between parent and child anxiety and parents' cognitions about their children. One hundred and four parents of children aged 3-5 years completed questionnaires regarding their own anxiety level, their child's anxiety level and their cognitions about the child, specifically parents' expectations about child distress and avoidance, and parents' perceived control over child mood and behaviour. Both parent anxiety and parent report of child anxiety were significantly associated with parents' cognitions. Specifically, parent report of child anxiety correlated significantly with parent locus of control generally and, more specifically, with parental expectations and perceived control of child anxious mood and behaviour. Parent anxiety correlated significantly with locus of control and parents' expectations of child anxious mood and behaviour. Furthermore, when both child and parent anxiety were taken into account, only parental anxiety remained significantly associated with parental locus of control and perceived control of child anxious behaviour. For parents' perceived control of child anxious mood, only child anxiety remained significantly associated. The results suggest that parents' perceived control over their children's behaviour may primarily reflect parental anxiety, rather than child anxiety. Parental anxiety may, therefore, present an important target for interventions that aim to change parent's cognitions and behaviour.

Detecting the number of signals using antenna array: a single threshold solution

A new approach is presented to identify the number of incoming signals in antenna array processing. The new method exploits the inherent properties existing in the noise eigenvalues of the covariance matrix of the array output. A single threshold has been established concerning information about the signal and noise strength, data length, and array size. When the subspace-based algorithms are adopted the computation cost of the signal number detector can almost be neglected. The performance of the threshold is robust against low SNR and short data length.

Olive oil increases the number of triacylglycerol-rich chylomicron particles compared with other oils: an effect retained when a second standard meal is fed

Background: Compared with the postprandial events after a single meal, different events occur when a second meal is ingested 4–6 h after a first meal. There is a rapid appearance of chylomicrons in the circulation carrying fat ingested with the first meal, with a peak 1 h after the second meal. Objective: Our goal was to examine whether different dietary oils have effects on the storage of triacylglycerol as a result of differences in their digestion, absorption, and incorporation into chylomicrons. Design: A single-blind, randomized, within-subject crossover design was used to study the effects of palm oil, safflower oil, a mixture of fish and safflower oil, and olive oil on postprandial apolipoprotein (apo) B-48, retinyl ester, and triacylglycerol in the Sf > 400 fraction with the use of a sequential meal protocol. Results: For triacylglycerol, retinyl ester, and apo B-48, the time to reach peak concentration was significantly earlier after the second meal than after the first meal (P < 0.005). This was apparent with each of the dietary oils. The pattern of the apo B-48 response differed significantly among the dietary oils, with olive oil resulting in higher concentrations after both meals (P = 0.003). The ratio of triacylglycerol to apo B-48 was significantly lower after olive oil feeding than after feeding with the other oils (P = 0.02). Conclusions: The rapid entry of chylomicrons after the ingestion of a second meal 5 h after a first meal was seen with all of the oils investigated. The short-term ingestion of olive oil produced more chylomicrons than did the other dietary oils, which may have been due to differences in the metabolic handling of olive oil within the gut.

Social equality in the number of choice options is represented in the ventromedial prefrontal cortex

A distinct aspect of the sense of fairness in humans is that we care not only about equality in material rewards but also about equality in non-material values. One such value is the opportunity to choose freely among many options, often regarded as a fundamental right to economic freedom. In modern developed societies, equal opportunities in work, living, and lifestyle are enforced by anti-discrimination laws. Despite the widespread endorsement of equal opportunity, no studies have explored how people assign value to it. We used functional magnetic resonance imaging to identify the neural substrates for subjective valuation of equality in choice opportunity. Participants performed a two-person choice task in which the number of choices available was varied across trials independently of choice outcomes. By using this procedure, we manipulated the degree of equality in choice opportunity between players and dissociated it from the value of reward outcomes and their equality. We found that activation in the ventromedial prefrontal cortex tracked the degree to which the number of options between the two players was equal. In contrast, activation in the ventral striatum tracked the number of options available to participants themselves but not the equality between players. Our results demonstrate that the vmPFC, a key brain region previously implicated in the processing of social values, is also involved in valuation of equality in choice opportunity between individuals. These findings may provide valuable insight into the human ability to value equal opportunity, a characteristic long emphasized in politics, economics, and philosophy.

Analysis of the distribution of the number of bidders in construction contract auctions

The number of bidders, N, involved in a construction procurement auction is known to have an important effect on the value of the lowest bid and the mark-up applied by bidders. In practice, for example, it is important for a bidder to have a good estimate of N when bidding for a current contract. One approach, instigated by Friedman in 1956, is to make such an estimate by statistical analysis and modelling. Since then, however, finding a suitable model for N has been an enduring problem for researchers and, despite intensive research activity in the subsequent 30 years, little progress has been made, due principally to the absence of new ideas and perspectives. The debate is resumed by checking old assumptions, providing new evidence relating to concomitant variables and proposing a new model. In doing this and in order to ensure universality, a novel approach is developed and tested by using a unique set of 12 construction tender databases from four continents. This shows the new model provides a significant advancement on previous versions. Several new research questions are also posed and other approaches identified for future study.

Rooting cuttings of Syringa vulgaris cv. Charles Joly and Corylus avellana cv. Aurea: the influence of stock plant pruning and shoot growth

The relationship between shoot growth and rooting was examined in two, 'difficult-to root' amenity trees, Syringa vulgaris L. cv. Charles Joly and Corylus avellana L. cv. Aurea. A range of treatments reflecting severity of pruning was imposed on field-grown stock prior to bud break. To minimise variation due to the numbers of buds that developed under different treatments, bud number was restricted to 30 per plant. Leafy cuttings were harvested at different stages of the active growth phase of each species. With Syringa, rooting decreased with later harvests, but loss of rooting potential was delayed in cuttings collected from the most severe pruning treatment. Rooting potential was associated with the extent of post-excision shoot growth on the cutting but regression analyses indicated that this relationship could not entirely explain the loss of rooting with time, nor the effects due to pruning. Similarly, in Corylus rooting was promoted by severe pruning, but the relationship between apical growth on the cutting and rooting was weaker than in Syringa, and only at the last harvest did growth play a critical role in determining rooting. Another unusual factor of the last harvest of Corylus was a bimodal distribution of roots per cutting, with very few rooted cuttings having less than five roots. This implies that, for this harvest at least, the potential of an individual cutting to root is probably not limited by the number of potential rooting sites.

Lock, stock, and barrel: a comprehensive assessment of the determinants of terror

We assess the robustness of previous findings on the determinants of terrorism. Using extreme bound analysis, the three most comprehensive terrorism datasets, and focusing on the three most commonly analyzed aspects of terrorist activity, i.e., location, victim, and perpetrator, we re-assess the effect of 65 proposed correlates. Evaluating around 13.4 million regressions, we find 18 variables to be robustly associated with the number of incidents occurring in a given country-year, 15 variables with attacks against citizens from a particular country in a given year, and six variables with attacks perpetrated by citizens of a particular country in a given year.

The development of anxiety disorders in childhood: an integrative review

We present an integrative review of the development of child anxiety, drawing on a number of strands of research. Family aggregation and genetic studies indicate raised vulnerability to anxiety in offspring of adults with the disorder (e.g. the temperamental style of behavioural inhibition, or information processing biases). Environmental factors are also important; these include adverse life events and exposure to negative information or modelling. Parents are likely to be key, although not unique, sources of such influences, particularly if they are anxious themselves. Some parenting behaviours associated with child anxiety, such as overprotection, may be elicited by child characteristics, especially in the context of parental anxiety, and these may serve to maintain child disorder. Emerging evidence emphasizes the importance of taking the nature of child and parental anxiety into account, of constructing assessments and interventions that are both disorder specific, and of considering bidirectional influences.

The effects of maternal depression and parental conflict on children's peer play

Background Little is known about the relative effects of exposure to postnatal depression and parental conflict on the social functioning of school-aged children. This is, in part, because of a lack of specificity in the measurement of child and parental behaviour and a reliance on children's reports of their hypothetical responses to conflict in play. Methods In the course of a prospective longitudinal study of children of postnatally depressed and well women, 5-year-old children were videotaped at home with a friend in a naturalistic dressing-up play setting. As well as examining possible associations between the occurrence of postnatal depression and the quality of the children's interactions, we investigated the influence of parental conflict and co-operation, and the continuity of maternal depression. The quality of the current mother-child relationship was considered as a possible mediating factor. Results Exposure to postnatal depression was associated with increased likelihood, among boys, of displaying physical aggression in play with their friend. However, parental conflict mediated the effects of postnatal depression on active aggression during play, and was also associated with displays of autonomy and intense conflict. While there were no gender effects in terms of the degree or intensity of aggressive behaviours, girls were more likely to express aggression verbally using denigration and gloating whereas boys were more likely to display physical aggression via interpersonal and object struggles. Conclusions The study provided evidence for the specificity of effects, with strong links between parental and child peer conflict. These effects appear to arise from direct exposure to parental conflict, rather than indirectly, through mother-child interactions.