Systemic recruitment of osteoblastic cells in fracture healing

We hypothesise that following a bone fracture there is systemic recruitment of bone forming cells to a fracture site. A rabbit ulnar osteotomy model was adapted to trace the movement of osteogenic cells. Bone marrow mesenchymal stem cells from 41 NZW rabbits were isolated, culture-expanded and fluorescently labelled. The labelled cells were either re-implanted into the fracture gap (Group A); into a vein (Group B); or into a remote tibial bone marrow cavity 48 h after the osteotomy (Group C) or 4 weeks before the osteotomy was established (Group D), and a control group (Group E) had no labelled cells given. To quantify passive leakage of cells to an injury site, inert beads were also co-delivered in Group B. Samples of the fracture callus tissue and various organs were harvested at discrete sacrifice time-points to trace and quantify the labelled cells. At 3 weeks following osteotomy, the number of labelled cells identified in the callus of Group C, was significantly greater than following IV delivery, Group B, and there was no difference in the number of labelled cells in the callus tissues, between Groups C and A, indicating the labelled bone marrow cells were capable of migrating to the fracture sites from the remote bone marrow cavity. Significantly fewer inert beads than labelled cells were identified in Group B callus, suggesting some of the bone-forming cells were actively recruited and selectively chosen to the fracture site, rather than passively leaked into the circulation and to bone injury site. This investigation supports the hypothesis that some osteoblasts involved in fracture healing were systemically mobilised and recruited to the fracture from remote bone marrow sites. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Microcomputed tomography imaging in a rat model of delayed union/non-union fracture

We aimed to develop a clinically relevant delayed union/non-union fracture model to evaluate a cell therapy intervention repair strategy. Histology, three-dimensional (3D) micro-computed tomography (micro-CT) imaging and mechanical testing were utilized to develop an analytical protocol for qualitative and quantitative assessment of fracture repair. An open femoral diaphyseal osteotomy, combined with periosteal diathermy and endosteal excision, was held in compression by a four pin unilateral external fixator. Three delayed union/non-union fracture groups established at 6 weeks-(a) a control group, (b) a cell therapy group, and (c) a group receiving phosphate-buffered saline (PBS) injection alone-were examined subsequently at 8 and 14 weeks. The histological response was combined fibrous and cartilaginous non-unions in groups A and B with fibrous non-unions in group C. Mineralized callus volume/total volume percentage showed no statistically significant differences between groups. Endosteal calcified tissue volume/endosteal tissue volume, at the center of the fracture site, displayed statistically significant differences between 8 and 14 weeks for cell and PBS intervention groups but not for the control group. The percentage load to failure was significantly lower in the control and cell treatment groups than in the PBS alone group. High-resolution micro-CT imaging provides a powerful tool to augment characterization of repair in delayed union/non-union fractures together with outcomes such as histology and mechanical strength measurement. Accurate, nondestructive, 3D identification of mineralization progression in repairing fractures is enabled in the presence or absence of intervention strategies. (c) 2007 Orthopaedic Research Society.

Cross-Cultural Patterns in Dynamic Ratings of Positive and Negative Natural Emotional Behaviour

Background: Studies of cross-cultural variations in the perception of emotion have typically compared rates of recognition of static posed stimulus photographs. That research has provided evidence for universality in the recognition of a range of emotions but also for some systematic cross-cultural variation in the interpretation of emotional expression. However, questions remain about how widely such findings can be generalised to real life emotional situations. The present study provides the first evidence that the previously reported interplay between universal and cultural influences extends to ratings of natural, dynamic emotional stimuli.

Methodology/Principal Findings: Participants from Northern Ireland, Serbia, Guatemala and Peru used a computer based tool to continuously rate the strength of positive and negative emotion being displayed in twelve short video sequences by people from the United Kingdom engaged in emotional conversations. Generalized additive mixed models were developed to assess the differences in perception of emotion between countries and sexes. Our results indicate that the temporal pattern of ratings is similar across cultures for a range of emotions and social contexts. However, there are systematic differences in intensity ratings between the countries, with participants from Northern Ireland making the most extreme ratings in the majority of the clips.

Conclusions/Significance: The results indicate that there is strong agreement across cultures in the valence and patterns of ratings of natural emotional situations but that participants from different cultures show systematic variation in the intensity with which they rate emotion. Results are discussed in terms of both ‘in-group advantage’ and ‘display rules’ approaches. This study indicates that examples of natural spontaneous emotional behaviour can be used to study cross-cultural variations in the perception of emotion.

Kinship, parentage and temporal stability in nursery colonies of Leisler’s bat (Nyctalus leisleri)

Levels of genetic relatedness within bat colonies are often unknown, and consequently the reasons for group formation and social organization are unclear. The Leisler's bat (Nyctalus leisleri), like most temperate bat species, forms nursery colonies in summer. We used microsatellite markers to examine identity and to attempt to estimate relatedness among females within a nursery colony, over 2 consecutive years, to ascertain whether females show kinship and natal philopatry, testing the hypothesis that this is the basis of colony formation. Parentage and relatedness of young born within a colony was assessed to investigate mating patterns via male reproductive skew and whether males achieve mating success within their natal colony. While there was evidence for female philopatry, levels of genetic relatedness within colonies were low. This suggests that kinship is not a major determinant in group formation, as roosts also comprise a large number of distant relatives or non-kin. Roost switching and gene flow are likely to be high. Both sexes reproduced in their first year, whereas males appear to be the more dispersive sex. We argue that the physical environment as well as information sharing provided by communal roosting are likely to be important factors for the formation of these large natal colonies in N. leisleri and possibly other lineages of bats. © 2012 The Author.

Animal group forces resulting from predator avoidance and competition minimization

A new model to explain animal spacing, based on a trade-off between foraging efficiency and predation risk, is derived from biological principles. The model is able to explain not only the general tendency for animal groups to form, but some of the attributes of real groups. These include the independence of mean animal spacing from group population, the observed variation of animal spacing with resource availability and also with the probability of predation, and the decline in group stability with group size. The appearance of "neutral zones" within which animals are not motivated to adjust their relative positions is also explained. The model assumes that animals try to minimize a cost potential combining the loss of intake rate due to foraging interference and the risk from exposure to predators. The cost potential describes a hypothetical field giving rise to apparent attractive and repulsive forces between animals. Biologically based functions are given for the decline in interference cost and increase in the cost of predation risk with increasing animal separation. Predation risk is calculated from the probabilities of predator attack and predator detection as they vary with distance. Using example functions for these probabilities and foraging interference, we calculate the minimum cost potential for regular lattice arrangements of animals before generalizing to finite-sized groups and random arrangements of animals, showing optimal geometries in each case and describing how potentials vary with animal spacing. (C) 1999 Academic Press.</p>

Steps to a better Belfast: physical activity assessment and promotion in primary care

BACKGROUND: Low physical activity (PA) levels which increase the risk of chronic disease are reported by two-thirds of the general UK population. Promotion of PA by primary healthcare professionals is advocated but more evidence is needed regarding effective ways of integrating this within everyday practice. This study aims to explore the feasibility of a randomised trial of a pedometer-based intervention, using step-count goals, recruiting patients from primary care. METHOD: Patients, aged 35-75, attending four practices in socioeconomically deprived areas, were invited to complete a General Practice PA Questionnaire during routine consultations. Health professionals invited 'inactive' individuals to a pedometer-based intervention and were randomly allocated to group 1 (prescribed a self-determined goal) or group 2 (prescribed a specific goal of 2500 steps/day above baseline). Both groups kept step-count diaries and received telephone follow-up at 1, 2, 6 and 11 weeks. Step counts were reassessed after 12 weeks. RESULTS: Of the 2154 patients attending, 192 questionnaires were completed (8.9%). Of these, 83 were classified as 'inactive'; 41(10 men; 31 women) completed baseline assessments, with the mean age of participants being 51 years. Mean baseline step counts were similar in group 1 (5685, SD 2945) and group 2 (6513, SD 3350). The mean increase in steps/day was greater in groups 1 than 2 ((2602, SD 1957) vs (748, SD 1997) p=0.005). CONCLUSIONS: A trial of a pedometer-based intervention using self-determined step counts appears feasible in primary care. Pedometers appear acceptable to women, particularly at a perimenopausal age, when it is important to engage in impact loading activities such as walking to maintain bone mineral density. An increase of 2500 steps/day is achievable for inactive patients, but the effectiveness of different approaches to realistic goal-setting warrants further study.

Assessing synchrony in groups:Are you measuring what you think you are measuring?

Behavioural synchrony has been a popular topic of research in group living animals, but has so far lacked a standard approach. Previous studies have varied greatly in the number of behavioural states they have considered and the size of groups investigated. Here, a model of behavioural synchrony was used to test four measures of synchrony commonly used (proportion observations 100% conforming, mean proportion of conforming individuals, Ruckstuhl's group mean and the kappa coefficient). The model used scan samples of the behaviour of laying hens, originally categorised in 10 different behavioural states, as a basis for determining the agents' probability of performing behaviour states. We systematically varied the group size and the number of behavioural states in the model. The measures calculated from the behaviour of the model agents were compared against a synchrony factor that determined the 'motivation' of agents in the model to conform to the behaviour of other agents, for model runs with different group sizes and behavioural categories. The results of the model suggest that, of the measures considered, the kappa coefficient is the most suitable measure of synchrony. The kappa coefficient was the only measure of the four tested to control for expected levels of synchrony. Expected levels of synchrony are sensitive to both the number of behaviour states being examined and the size of the group, therefore observed levels of synchrony should be compared against expected levels to provide meaningful standardised measures. © 2012 Elsevier B.V.

Progression of retinal pigment epithelial atrophy in stargardt disease

• PURPOSE: To evaluate retinal pigment epithelial (RPE) atrophy in patients with Stargardt disease using autofluorescence imaging (AF). • DESIGN: Retrospective observational case series. • METHODS: Demographics, best-corrected visual acuity (BCVA), AF images, and electrophysiology responses (group 1, macular dysfunction; group 2, macula + cone dysfunction; group 3, macula + cone-rod dysfunction) were evaluated at presentation and follow-up in a group of 12 patients (24 eyes) with Stargardt disease. The existence, development, and rate of enlargement of areas of RPE atrophy over time were evaluated using AF imaging. A linear regression model was used to investigate the effects of AF and electrophysiology on rate of atrophy enlargement and BCVA, adjusting for age of onset and duration of disease. • RESULTS: Eight male and 4 female patients (median age 42 years; range 24-69 years) were followed for a median of 41.5 months (range 13-66 months). All 12 patients had reduced AF compatible with RPE atrophy at presentation and in all patients the atrophy enlarged during follow-up. The mean rate of atrophy enlargement for all patients was 1.58 mm /y (SD 1.25 mm /y; range 0.13-5.27 mm /y). Only the pattern of functional loss present as detected by electrophysiology was statistically significantly associated with the rate of atrophy enlargement when correcting for other variables (P <.001), with patients in group 3 (macula + cone-rod dysfunction) having the fastest rate of atrophy enlargement (1.97 mm /y, SD 0.70 mm /y) (group 1 [macula] 1.09 mm /y, SD 0.53 mm /y; group 2 [macula + cone] 1.89 mm /y, SD 2.27 mm /y). • CONCLUSION: Variable rates of atrophy enlargement were observed in patients with Stargardt disease. The pattern of functional loss detected on electrophysiology was strongly associated with the rate of atrophy enlargement over time, thus serving as the best prognostic indicator for patients with this inherited retinal disease. © 2012 Elsevier Inc. All rights reserved.

Freshwater pearl mussels show plasticity of responses to different predation risks but also show consistent individual differences in responsiveness

Animals often show behavioural plasticity with respect to predation risk but also show behavioural syndromes in terms of consistency of responses to different stimuli. We examine these features in the freshwater pearl mussel. These bivalves often aggregate presumably to reduce predation risk to each individual. Predation risk, however, will be higher in the presence of predator cues. Here we use dimming light, vibration and touch as novel stimuli to examine the trade-off between motivation to feed and motivation to avoid predation. We present two experiments that each use three sequential novel stimuli to cause the mussels to close their valves and hence cease feeding. We find that mussels within a group showed shorter closure times than solitary mussels, consistent with decreased vulnerability to predation in group-living individuals. Mussels exposed to the odour of a predatory crayfish showed longer closures than control mussels, highlighting the predator assessment abilities of this species. However, individuals showed significant consistency in their closure responses across the trial series, in line with behavioural syndrome theory. Our results show that bivalves trade-off feeding and predator avoidance according to predation risk but the degree to which this is achieved is constrained by behavioural consistency. © 2011 Elsevier B.V.

Social Identity and Youth Aggressive and Delinquent Behaviors in a Context of Political Violence

The goal of the current study was to examine the moderating role of in-group social identity on relations between youth exposure to sectarian antisocial behavior in the community and aggressive behaviors. Participants included 770 mother-child dyads living in interfaced neighborhoods of Belfast. Youth answered questions about aggressive and delinquent behaviors as well as the extent to which they targeted their behaviors toward members of the other group. Structural equation modeling results show that youth exposure to sectarian antisocial behavior is linked with increases in both general and sectarian aggression and delinquency over one year. Reflecting the positive and negative effects of social identity, in-group social identity moderated this link, strengthening the relationship between exposure to sectarian antisocial behavior in the community and aggression and delinquency towards the out-group. However, social identity weakened the effect for exposure to sectarian antisocial behavior in the community on general aggressive behaviors. Gender differences also emerged; the relation between exposure to sectarian antisocial behavior and sectarian aggression was stronger for boys. The results have implications for understanding the complex role of social identity in intergroup relations for youth in post-accord societies.

Social effects of collaborative learning in primary schools

There is conflicting evidence on whether collaborative group work leads to improved classroom relations, and if so how. A before and after design was used to measure the impact on work and play relations of a collaborative learning programme involving 575 students 9e12 years old in single- and mixed-age classes across urban and rural schools. Data were also collected on student interactions and teacher ratings of their group-work skills. Analysis of variance revealed significant gains for both types of relation. Multilevel modelling indicated that better work relations were the product of improving group skills, which offset tensions produced by transactive dialogue, and this effect fed through in turn to play relations. Although before intervention rural children were familiar with each other neither this nor age mix affected outcomes. The results suggest the social benefits of collaborative learning are a separate outcome of group work, rather than being either a pre-condition for, or a direct consequence of successful activity, but that initial training in group skills may serve to enhance these benefits.

Supernatural Beliefs, Unconscious Threat and Judgment Bias in Tibetan Buddhists

Individuals who have been subtly reminded of death display heightened in-group favouritism, or “worldview defense.” Terror management theory argues (i) that death cues engender worldview defense via psychological mechanisms specifically evolved to suppress death anxiety, and (ii) that the core function of religiosity is to suppress death anxiety. Thus, terror management theory predicts that extremely religious individuals will not evince worldview defense. Here, two studies are presented in support of an alternative perspective. According to the unconscious vigilance hypothesis, subtly processed threats (which need not pertain to death) heighten sensitivity to affectively valenced stimuli (which need not pertain to cultural attitudes). From this perspective, religiosity mitigates the influence of mortality-salience only insofar as afterlife doctrines reduce the perceived threat posed by death. Tibetan Buddhism portrays death as a perilous gateway to rebirth rather than an end to suffering; faith in this doctrine should therefore not be expected to nullify mortality-salience effects. In Study 1, devout Tibetan Buddhists who were subtly reminded of death produced exaggerated aesthetic ratings unrelated to cultural worldviews. In Study 2, devout Tibetan Buddhists produced worldview defense following subliminal exposure to non-death cues of threat. The results demonstrate both the domain-generality of the process underlying worldview defense and the importance of religious doctrinal content in moderating mortality-salience effects.

Utilising a computer game as a therapeutic intervention for youth in residential care: Some preliminary findings on use and acceptability

Mental illness is common amongst young people living in residential care, many of whom are reluctant to avail of therapeutic help. The potential value of computer games as therapeutic tools for these young people has received very little attention, despite indications of their potential for promoting engagement in therapeutic work and improving mental health outcomes. This study aimed to fill this research gap through the development, introduction, and preliminary evaluation of a therapeutic intervention in group care settings. The intervention incorporated a commercially available computer game (The SIMS Life Stories™) and emotion regulation skill coaching. Qualified residential social workers were trained to deliver it to young people in three children's homes in Northern Ireland, where therapeutic approaches to social work had been introduced. The research was framed as an exploratory case study which aimed to determine the acceptability and potential therapeutic value of this intervention. The evidence suggests that computer-game based interventions of this type may have value as therapeutic tools in group care settings and deserve further development and empirical investigation to determine their effectiveness in improving mental health outcomes.

DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach

BACKGROUND: Methylation-induced silencing of promoter CpG islands in tumor suppressor genes plays an important role in human carcinogenesis. In colorectal cancer, the CpG island methylator phenotype (CIMP) is defined as widespread and elevated levels of DNA methylation and CIMP+ tumors have distinctive clinicopathological and molecular features. In contrast, the existence of a comparable CIMP subtype in gastric cancer (GC) has not been clearly established. To further investigate this issue, in the present study we performed comprehensive DNA methylation profiling of a well-characterised series of primary GC.

METHODS: The methylation status of 1,421 autosomal CpG sites located within 768 cancer-related genes was investigated using the Illumina GoldenGate Methylation Panel I assay on DNA extracted from 60 gastric tumors and matched tumor-adjacent gastric tissue pairs. Methylation data was analysed using a recursively partitioned mixture model and investigated for associations with clinicopathological and molecular features including age, Helicobacter pylori status, tumor site, patient survival, microsatellite instability and BRAF and KRAS mutations.

RESULTS: A total of 147 genes were differentially methylated between tumor and matched tumor-adjacent gastric tissue, with HOXA5 and hedgehog signalling being the top-ranked gene and signalling pathway, respectively. Unsupervised clustering of methylation data revealed the existence of 6 subgroups under two main clusters, referred to as L (low methylation; 28% of cases) and H (high methylation; 72%). Female patients were over-represented in the H tumor group compared to L group (36% vs 6%; P = 0.024), however no other significant differences in clinicopathological or molecular features were apparent. CpG sites that were hypermethylated in group H were more frequently located in CpG islands and marked for polycomb occupancy.

CONCLUSIONS: High-throughput methylation analysis implicates genes involved in embryonic development and hedgehog signaling in gastric tumorigenesis. GC is comprised of two major methylation subtypes, with the highly methylated group showing some features consistent with a CpG island methylator phenotype.

Evolution of Hot Loops in an Active Region Core Observed with the SDO Atmospheric Image Assembly

Evidence has accumulated of high temperature (> 4 MK) coronal emission in active region cores that corresponds to structures in equilibrium. Other studies have found evidence of evolving loops. We investigate the EUV intensity and temperature variations of short coronal loops observed in the core of NOAA Active Region 11250 on 13 July 2011. The loops, which run directly between the AR opposite polarities, are first detectable in the 94Å band of Fe XVIII, implying an effective temperature ~ 7 MK. The low temperature component of the 94 Å signal is modeled in terms of a linear superposition of the 193 Å and 171 Å signals in order to separate the hot component. After identifying the loops we have used contemporaneous HMI observations to identify the corresponding inter-moss regions, and we have investigated their time evolution in six AIA EUV channels. The results can be separated into two classes. Group 1 (94Å, 335Å, 211Å) is characterized by hotter temperatures (~2-7 MK), and Group 2 (193Å, 171Å, 131Å) by cooler temperatures (0.4 - 1.6 MK). For Group 1 the intensity peaks in the 94Å channel are followed by maxima in the 335 Å channel with a time lag of ~8 min, suggestive of a cooling pattern with an exponential decay. While the 211Å maxima follow those in the 335 Å channel, there is no systematic relation which would indicate a progressive cooling process through the lower temperatures, as has been observed in other investigations. In Group 2 the signals in the 171 and 131Å channels track each other closely, and lag behind the 193Å. In the inter-moss region of the loop the peak temperature and peak emission measure have opposite trends. The hot 94Å brightenings occur in the central part of the loops with maximum temperatures ~7 MK. Subsequently the loops appear to fill with plasma with an emission measure compatible with the 193 Å signal and temperature in the range ~ 1.5-2 MK. Although the exact details of the time evolution are still under investigation, these non static loops show high levels of intermittency in the 94Å signal (please see poster "Intermittent and Scale-Invariant Intensity Fluctuations in Hot Coronal Loops," by Lawrence et al. in this session).