A comparison of the development of audiovisual integration in children with autism spectrum disorders and typically developing children

This study aimed to investigate the development of audiovisual integration in children with Autism Spectrum Disorder (ASD). Audiovisual integration was measured using the McGurk effect in children with ASD aged 7–16 years and typically developing children (control group) matched approximately for age, sex, nonverbal ability and verbal ability. Results showed that the children with ASD were delayed in visual accuracy and audiovisual integration compared to the control group. However, in the audiovisual integration measure, children with ASD appeared to ‘catch-up’ with their typically developing peers at the older age ranges. The suggestion that children with ASD show a deficit in audiovisual integration which diminishes with age has clinical implications for those assessing and treating these children

A targeted decision aid for the elderly to decide whether to undergo colorectal cancer screening: development and results of an uncontrolled trial

Abstract: Background: Competing causes of mortality in the elderly decrease the potential net benefit from colorectal cancer screening and increase the likelihood of potential harms. Individualized decision making has been recommended, so that the elderly can decide whether or not to undergo colorectal cancer (CRC) screening. The objective is to develop and test a decision aid designed to promote individualized colorectal cancer screening decision making for adults age 75 and over. Methods: We used formative research and cognitive testing to develop and refine the decision aid. We then tested the decision aid in an uncontrolled trial. The primary outcome was the proportion of patients who were prepared to make an individualized decision, defined a priori as having adequate knowledge (10/15 questions correct) and clear values (25 or less on values clarity subscale of decisional conflict scale). Secondary outcomes included overall score on the decisional conflict scale, and preferences for undergoing screening. Results: We enrolled 46 adults in the trial. The decision aid increased the proportion of participants with adequate knowledge from 4% to 52% (p < 0.01) and the proportion prepared to make an individualized decision from 4% to 41% (p < 0.01). The proportion that preferred to undergo CRC screening decreased from 67% to 61% (p = 0. 76); 7 participants (15%) changed screening preference (5 against screening, 2 in favor of screening) Conclusion: In an uncontrolled trial, the elderly participants appeared better prepared to make an individualized decision about whether or not to undergo CRC screening after using the decision aid

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Hexamerization-enhanced CD20 antibody mediates complement-dependent cytotoxicity in serum genetically deficient in C9

We examined complement-dependent cytotoxicity (CDC) by hexamer formation-enhanced CD20 mAb Hx-7D8 of patient-derived chronic lymphocytic leukemia (CLL) cells that are relatively resistant to CDC. CDC was analyzed in normal human serum (NHS) and serum from an individual genetically deficient for C9. Hx-7D8 was able to kill up to 80% of CLL cells in complete absence of C9. We conclude that the narrow C5b-8 pores formed without C9 are sufficient for CDC due to efficient antibody-mediated hexamer formation. In the absence of C9, we observed transient intracellular increases of Ca2 + during CDC (as assessed with FLUO-4) that were extended in time. This suggests that small C5b-8 pores allow Ca2 + to enter the cell, while dissipation of the fluorescent signal accompanying cell disintegration is delayed. The Ca2 + signal is retained concomitantly with TOPRO-3 (viability dye) staining, thereby confirming that Ca2 + influx represents the most proximate mediator of cell death by CDC

Factors affecting medical students in formulating their specialty preferences in Jordan

<p>Abstract</p> <p>Background</p> <p>In recent years there has been a growing appreciation of the issues of career preference in medicine as it may affect student learning and academic performance. However, no such studies have been undertaken in medical schools in Jordan. Therefore, we carried out this study to investigate the career preferences of medical students at Jordan University of Science and Technology and determine factors that might influence their career decisions.</p> <p>Methods</p> <p>A cross-sectional questionnaire-based survey was carried out among second, fourth and sixth year medical students at the Jordan University of Science and Technology, Irbid, Jordan during the academic year 2006/2007. A total of 440 students answered the questionnaire which covered demographic characteristics, specialty preferences, and the factors that influenced these career preferences. Possible influences were selected on the basis of a literature review and discussions with groups of medical students and physicians. Students were asked to consider 14 specialty options and select the most preferred career preference.</p> <p>Results</p> <p>The most preferred specialty expressed by male students was surgery, followed by internal medicine and orthopaedics, while the specialty most preferred by female students was obstetrics and gynaecology, followed by pediatrics and surgery. Students showed little interest in orthopedics, ophthalmology, and dermatology. While 3.1% of females expressed interest in anesthesiology, no male students did. Other specialties were less attractive to most students.</p> <p>Intellectual content of the specialty and the individual's competencies were the most influential on their preference of specialty. Other influential factors were the "reputation of the specialty", "anticipated income", and "focus on urgent care".</p> <p>Conclusion</p> <p>Surgery, internal medicine, pediatrics, and obstetrics and gynaecology were the most preferred specialty preferences of medical students at Jordan University of Science and Technology.</p

Coulomb Interactions between Cytoplasmic Electric Fields and Phosphorylated Messenger Proteins Optimize Information Flow in Cells

Normal cell function requires timely and accurate transmission of information from receptors on the cell membrane (CM) to the nucleus. Movement of messenger proteins in the cytoplasm is thought to be dependent on random walk. However, Brownian motion will disperse messenger proteins throughout the cytosol resulting in slow and highly variable transit times. We propose that a critical component of information transfer is an intracellular electric field generated by distribution of charge on the nuclear membrane (NM). While the latter has been demonstrated experimentally for decades, the role of the consequent electric field has been assumed to be minimal due to a Debye length of about 1 nanometer that results from screening by intracellular Cl- and K+. We propose inclusion of these inorganic ions in the Debye-Huckel equation is incorrect because nuclear pores allow transit through the membrane at a rate far faster than the time to thermodynamic equilibrium. In our model, only the charged, mobile messenger proteins contribute to the Debye length.Using this revised model and published data, we estimate the NM possesses a Debye-Huckel length of a few microns and find this is consistent with recent measurement using intracellular nano-voltmeters. We demonstrate the field will accelerate isolated messenger proteins toward the nucleus through Coulomb interactions with negative charges added by phosphorylation. We calculate transit times as short as 0.01 sec. When large numbers of phosphorylated messenger proteins are generated by increasing concentrations of extracellular ligands, we demonstrate they generate a self-screening environment that regionally attenuates the cytoplasmic field, slowing movement but permitting greater cross talk among pathways. Preliminary experimental results with phosphorylated RAF are consistent with model predictions.This work demonstrates that previously unrecognized Coulomb interactions between phosphorylated messenger proteins and intracellular electric fields will optimize information transfer from the CM to the NM in cells

Effect of an antepartum Pap smear on the coverage of a cervical cancer screening programme: a population-based prospective study

BACKGROUND: Almost one-third of Norwegian women aged 25–69 years invited to have a Pap smear do not attend during the recommended period, and thus constitute a population with high-risk of cervical cancer (CC). Since the incidence of precancerous lesions of the cervix peak with occurrence of pregnancies within the same decade in women aged 25 to 35 years of age, antepartum care presents an opportunity to offer a Pap smear thereby increasing the coverage of the programme. The study objective was to describe the effect of the antepartum Pap smear on the coverage of a cytological CC screening programme. METHODS: Among 2 175 762 women resident in Norway in 31.12.1996, all women who gave birth in 1996–7 were identified from the Medical Birth Registry of Norway. Attendance to the cervical cancer screening was assessed by linkage to the Cytology Registry separately for the pregnant and non-pregnant women cohorts. The results were stratified by age, history of previous Pap smear and history of invitation to the CC screening programme. Logistic regression was used to estimate the relative probabilities of having a Pap smear adjusted for age, screening history, and time since invitation, for pregnant and non-pregnant women, respectively. RESULTS: 69% of the pregnant women had a Pap smear during one year of follow-up since beginning of the pregnancy with the majority taken during the antepartum period. Irrespectively of age or history of having a Pap smear, pregnant women were 4.3 times more likely to have a Pap smear during follow-up compared to non-pregnant women. 63.2% of the pregnant women had a smear as response to the invitation letter compared to 28.7% of the non-pregnant women, OR = 2.1 (95% CI 1.9 to 2.4). As an indication of "over-screening", 5397 pregnant women (57.8%) with a smear shortly before the start of follow-up also had a new Papsmear, compared to 83 023 (32.3%) in non-pregnant. CONCLUSION: Pap smear screening during pregnancy increases the coverage of the CC screening programme. The contribution of the antepartum Pap smear to "over-screening" exists but its effect is modest in countries where women on average become pregnant after the start of recommended age of screening

Regulation of signal duration and the statistical dynamics of kinase activation by scaffold proteins

Scaffolding proteins that direct the assembly of multiple kinases into a spatially localized signaling complex are often essential for the maintenance of an appropriate biological response. Although scaffolds are widely believed to have dramatic effects on the dynamics of signal propagation, the mechanisms that underlie these consequences are not well understood. Here, Monte Carlo simulations of a model kinase cascade are used to investigate how the temporal characteristics of signaling cascades can be influenced by the presence of scaffold proteins. Specifically, we examine the effects of spatially localizing kinase components on a scaffold on signaling dynamics. The simulations indicate that a major effect that scaffolds exert on the dynamics of cell signaling is to control how the activation of protein kinases is distributed over time. Scaffolds can influence the timing of kinase activation by allowing for kinases to become activated over a broad range of times, thus allowing for signaling at both early and late times. Scaffold concentrations that result in optimal signal amplitude also result in the broadest distributions of times over which kinases are activated. These calculations provide insights into one mechanism that describes how the duration of a signal can potentially be regulated in a scaffold mediated protein kinase cascade. Our results illustrate another complexity in the broad array of control properties that emerge from the physical effects of spatially localizing components of kinase cascades on scaffold proteins.Comment: 12 pages, 6 figure