Teasing Apart the Impact of Illness and IQ on Functional Neuroimaging Findings in Schizophrenia

Schizophrenia is a major psychiatric disorder associated with cognitive impairment. Functional brain imaging (fMRI) studies of schizophrenia patients reveal a complex pattern of brain differences in the prefrontal cortex. Both decreased (hypofrontality) and increased (hyperfrontality) activity have been reported in patients – inconsistencies that this paper argues could be explained by differences in IQ between patients and healthy controls. This study demonstrates a novel method to tease apart IQ and schizophrenia effects on brain activity. Twelve schizophrenia patients were matched to twelve healthy controls matched to patients’ estimated (premorbid) IQ before their illness, and twelve healthy controls matched to patients’ measured current IQ. All participants performed an executive function event-related fMRI task. Schizophrenia patients’ mean behavioral scores fell numerically between those of both control groups, and did not differ significantly from either group. Two distinct patterns of brain activity were found that were consistent with an effect due to either IQ impairment or schizophrenia diagnosis. Schizophrenia patients’ relatively reduced activity in middle/superior frontal (BA6/BA8) regions was related to their schizophrenia diagnosis, whereas their relatively increased activity in inferior frontal (BA44/45) and left middle frontal (BA8/9) regionsrelated instead to their current IQ impairment. These findings indicate that some fMRI differences reported in schizophrenia patients are artefacts of IQ matching. After removing the IQ confounds, schizophrenia was associated with lateral frontal hypoactivations and medial frontal failure of deactivation. This paper proposes a method to address IQ matching-related issues when studying populations where their illness involves cognitive deterioration

The effects of supernovae on the dynamical evolution of binary stars and star clusters

In this chapter I review the effects of supernovae explosions on the dynamical evolution of (1) binary stars and (2) star clusters. (1) Supernovae in binaries can drastically alter the orbit of the system, sometimes disrupting it entirely, and are thought to be partially responsible for `runaway' massive stars - stars in the Galaxy with large peculiar velocities. The ejection of the lower-mass secondary component of a binary occurs often in the event of the more massive primary star exploding as a supernova. The orbital properties of binaries that contain massive stars mean that the observed velocities of runaway stars (10s - 100s km s$^{-1}$) are consistent with this scenario. (2) Star formation is an inherently inefficient process, and much of the potential in young star clusters remains in the form of gas. Supernovae can in principle expel this gas, which would drastically alter the dynamics of the cluster by unbinding the stars from the potential. However, recent numerical simulations, and observational evidence that gas-free clusters are observed to be bound, suggest that the effects of supernova explosions on the dynamics of star clusters are likely to be minimal.Comment: 16 pages, to appear in the 'Handbook of Supernovae', eds. Paul Murdin and Athem Alsabti. This version replaces an earlier version that contained several typo

‘Do I have the capacity to make capacity judgements?’ Researcher reflections from a person-centred dementia support study

Background and purpose Adults lacking capacity are under-represented in research; therefore, the evidence-base surrounding their support needs is inferior compared to other populations. Involving this group in research is fraught with challenges, including researcher uncertainties about how to carry out capacity judgements. Whilst ethical guidelines and principles provide overarching guidance, there is a lack of detailed guidance and evidence-based training, incorporating practical ‘on the ground’ strategies and advice on communication practices. Experiences and reflections on research procedures used to gauge and address capacity are under reported, resulting in a lack of shared knowledge within the field. Design To help address this, we engaged in researcher (co)meta-reflection on the informed capacity judgement procedure for initial consent, within our current, person-centred dementia intervention feasibility study. Our objective was to identify areas to improve our approach, but to also put forward suggestions for wider change within ethical research practice. Results Findings reveal challenges and facilitators relating to six areas: ‘Conducting time sensitive research whilst remaining person-centred and building relationships’; ‘Information sharing and supporting communication’; ‘Applying the process flexibly’; ‘The role of the carer and the consultee process’; ‘Judging assent and dissent’ and ‘Researcher related factors’. We questioned our ‘capacity to make capacity judgements’ in terms of both our skills and research time constraints. Conclusions Based on our experiences, we argue for greater open discussion between researchers, Patient and Public Involvement contributors and Research Ethics Committees at initial project planning stages. We recommend training and guidance focuses on building researcher skills in applying a standard process flexibly, emphasising naturalistic, conversational approaches to capacity judgement. A crucial consideration for funders is how this time-intensive and sensitive work should be factored into bid application templates and funding grants. Learnings from this article have potential to inform evidence-based guidance and training for researchers, consultees, funders, reviewers and ethics committees. </jats:sec

Fear and Courage in Children: Two Sides of the Same Coin?

This study further investigated the construct of courage in children. Children aged 8–13 years (n = 51) were interviewed about the most courageous action that they had ever performed during their life, and to retrospectively rate their level of fear and courage experienced during that event. On a separate occasion, children also completed the Courage Measure for Children (CM-C) as an index of children’s general level of personal courage, as well as scales for assessing anxiety symptoms and sensation seeking. Results indicated that almost all children (i.e., 94%) indicated that they had carried out a courageous action at some point during their life, although the levels of fear and courage associated with these acts varied considerably. Further, there was no relation between fear and courage reported for the courageous action, but these variables were significantly correlated with respectively anxiety symptoms and personal courage as indexed by the CM-C. Finally, a significant positive correlation was observed between sensation seeking and personal courage, indicating that children who are more thrill and adventure seeking are generally also more courageous. It is concluded that fear and courage in children are largely unrelated and not just two sides of the same coin. The implications of these results for the etiology and treatment of childhood anxiety problems are discussed

Synchronous bursts on scale-free neuronal networks with attractive and repulsive coupling

This paper investigates the dependence of synchronization transitions of bursting oscillations on the information transmission delay over scale-free neuronal networks with attractive and repulsive coupling. It is shown that for both types of coupling, the delay always plays a subtle role in either promoting or impairing synchronization. In particular, depending on the inherent oscillation period of individual neurons, regions of irregular and regular propagating excitatory fronts appear intermittently as the delay increases. These delay-induced synchronization transitions are manifested as well-expressed minima in the measure for spatiotemporal synchrony. For attractive coupling, the minima appear at every integer multiple of the average oscillation period, while for the repulsive coupling, they appear at every odd multiple of the half of the average oscillation period. The obtained results are robust to the variations of the dynamics of individual neurons, the system size, and the neuronal firing type. Hence, they can be used to characterize attractively or repulsively coupled scale-free neuronal networks with delays.Comment: 15 pages, 9 figures; accepted for publication in PLoS ONE [related work available at http://arxiv.org/abs/0907.4961 and http://www.matjazperc.com/

“You Might Belong in Gryffindor”: Children’s Courage and Its Relationships to Anxiety Symptoms, Big Five Personality Traits, and Sex Roles

This study describes a first exploration of the construct of courage in youths. Children aged 8–13 years were invited to report on the most courageous action that they had ever performed during their life. In addition, the Courage Measure for Children (CM-C) was construed as an index of children’s level of personal courage, and this scale was administered in two samples of school children (Ns being 168 and 159) along with a number of other questionnaires. Results indicated that children were familiar with the concept of courage as more than 70% reported to have carried out a courageous action during their life. In addition, self-reported courage as indexed by the CM-C was positively correlated with scores on a vignette measure of courage, parent ratings of children’s courage, extraversion, openness/intellect, and a masculine sex role, whereas a negative correlation was observed with anxiety symptoms. The implications of these findings and potential directions for future research are briefly discussed

Car make and model recognition under limited lighting conditions at night

Car make and model recognition (CMMR) has become an important part of intelligent transport systems. Information provided by CMMR can be utilized when license plate numbers cannot be identified or fake number plates are used. CMMR can also be used when a certain model of a vehicle is required to be automatically identified by cameras. The majority of existing CMMR methods are designed to be used only in daytime when most of the car features can be easily seen. Few methods have been developed to cope with limited lighting conditions at night where many vehicle features cannot be detected. The aim of this work was to identify car make and model at night by using available rear view features. This paper presents a one-class classifier ensemble designed to identify a particular car model of interest from other models. The combination of salient geographical and shape features of taillights and license plates from the rear view is extracted and used in the recognition process. The majority vote from support vector machine, decision tree, and k-nearest neighbors is applied to verify a target model in the classification process. The experiments on 421 car makes and models captured under limited lighting conditions at night show the classification accuracy rate at about 93 %

Antiproliferative effect of immunoliposomes containing 5-fluorodeoxyuridine-dipalmitate on colon cancer cells

We have investigated the antiproliferative action towards CC531 colon adenocarcinoma cells of target cell-specific immunoliposomes containing the amphiphilic dipalmitoyl derivative of 5-fluorodeoxyuridine (FUdR-dP). FUdR-dP incorporated in immunoliposomes caused a 13-fold stronger inhibition of CC531 cell growth in vitro, during a 72-h treatment, than FUdR-dP in liposomes without antibody, demonstrating that the prodrug is efficiently hydrolysed to yield the active drug, FUdR, intracellularly. The intracellular release of active FUdR was confirmed by determining the fate of H-3-labelled immunoliposomal FUdR-dP. Treatments shorter than 72 h with FUdR-dP in immunoliposomes resulted in anti-tumour activities comparable to, or even higher than, that of free FUdR. The shorter treatments reflect more closely the in vivo situation and illustrate the potential advantage of the use of immunoliposomes over non-targeted liposomal FUdR-dP or free FUdR. Association of tumour cell-specific immunoliposomes with CC531 cells was up to tenfold higher than that of liposomes without antibody or with irrelevant IgG coupled, demonstrating a specific interaction between liposomes and target cells which causes an efficient intracellular delivery of the drug. Since biochemical evidence indicates a lack of internalization or degradation of the liposomes as such; we postulate that entry of the drug most likely involves the direct transfer of the prodrug from the immunoliposome to the cell membrane during its antigen-specific interaction with the cells. followed by hydrolysis of FUdR-dP leading to relatively high intracellular FUdR-levels. In conclusion, we describe a targeted liposomal formulation for the anticancer drug FUdR, which is able to deliver the active drug to colon carcinoma cells with high efficiency, without the need for the cells to internalize the liposomes as such

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph