The development of path integration: combining estimations of distance and heading

Efficient daily navigation is underpinned by path integration, the mechanism by which we use self-movement information to update our position in space. This process is well-understood in adulthood, but there has been relatively little study of path integration in childhood, leading to an underrepresentation in accounts of navigational development. Previous research has shown that calculation of distance and heading both tend to be less accurate in children as they are in adults, although there have been no studies of the combined calculation of distance and heading that typifies naturalistic path integration. In the present study 5-year-olds and 7-year-olds took part in a triangle-completion task, where they were required to return to the startpoint of a multi-element path using only idiothetic information. Performance was compared to a sample of adult participants, who were found to be more accurate than children on measures of landing error, heading error, and distance error. 7-year-olds were significantly more accurate than 5-year-olds on measures of landing error and heading error, although the difference between groups was much smaller for distance error. All measures were reliably correlated with age, demonstrating a clear development of path integration abilities within the age range tested. Taken together, these data make a strong case for the inclusion of path integration within developmental models of spatial navigational processing

Route planning with transportation network maps: an eye-tracking study.

Planning routes using transportation network maps is a common task that has received little attention in the literature. Here, we present a novel eye-tracking paradigm to investigate psychological processes and mechanisms involved in such a route planning. In the experiment, participants were first presented with an origin and destination pair before we presented them with fictitious public transportation maps. Their task was to find the connecting route that required the minimum number of transfers. Based on participants' gaze behaviour, each trial was split into two phases: (1) the search for origin and destination phase, i.e., the initial phase of the trial until participants gazed at both origin and destination at least once and (2) the route planning and selection phase. Comparisons of other eye-tracking measures between these phases and the time to complete them, which depended on the complexity of the planning task, suggest that these two phases are indeed distinct and supported by different cognitive processes. For example, participants spent more time attending the centre of the map during the initial search phase, before directing their attention to connecting stations, where transitions between lines were possible. Our results provide novel insights into the psychological processes involved in route planning from maps. The findings are discussed in relation to the current theories of route planning

Meta-Analysis of the Association between Transforming Growth Factor-Beta Polymorphisms and Complications of Coronary Heart Disease

Objective: To investigate the association between common transforming growth factor beta (TGF-β) single nucleotide polymorphisms (SNP) and significant complications of coronary heart disease (CHD).\ud \ud Method: We performed a meta-analysis of published case-control studies assessing the association of TGF-β SNPs with a range of CHD complications. A random effects model was used to calculate odds ratios and confidence intervals. Analyses were conducted for additive, dominant and recessive modes of inheritance.\ud \ud Results: Six studies involving 5535 cases and 2970 controls examining the association of common SNPs in TGF-β1 with CHD were identified. Applying a dominant model of inheritance, three TGF-β1 SNPs were significantly associated with CHD complications: The T alleles of rs1800469 (OR = 1.125, 95% CI 1.016–1.247, p = 0.031) and rs1800470 (OR = 1.146, 95% CI 1.026–1.279, p = 0.021); and the C allele of rs1800471 (OR = 1.207, 95% CI 1.037–1.406, p = 0.021).\ud \ud Conclusion: This meta-analysis suggests that common genetic polymorphisms in TGF-β1 are associated with complications of CHD

Gene expression differences between stroke-associated and asymptomatic carotid plaques

Atherosclerotic carotid stenosis is an important risk factor for stroke. Carotid plaques (CPs) causing stroke may present a distinct type of molecular pathology compared with transient ischemic attack (TIA)-associated or asymptomatic plaques. We compared the gene expression profiles of CPs from stroke patients (n = 12) and asymptomatic patients (n = 9), both with similar risk factors and severity of carotid stenosis (>70%). Sixty probes showed over 1.5-fold expression difference at 5% false discovery rate. Functional clustering showed enrichment of genes in 51 GO categories and seven pathways, the most significant of which relate to extracellular-matrix interaction, PPAR gamma signaling, scavanger receptor activity, and lysosomal activity. Differential expression of ten genes was confirmed in an extended replication group (n = 43), where the most significant expression differences were found in CD36 (2.1-fold change, p = 0.005), CD163 (1.7-fold change, p = 0.007) and FABP4 (2.2-fold change, p = 0.015). These include four genes not previously linked to plaque destabilization: GLUL (2.2-fold change, p = 0.016), FUCA1 (2.2-fold change, p = 0.025), IL1RN (1.6-fold change, p = 0.034), and S100A8 (2.5-fold change, p = 0.047). Strong correlations were found to plaque ulceration, plaque hemorrhage, and markers of apoptosis and proliferation (activated caspase 3, TUNEL, and Ki67). Protein expression of these genes was confirmed by immunohistochemistry and was found in the atheromatous areas of CPs critical for plaque destabilization. This study presents a comprehensive transcriptional analysis of stroke-associated CPs and demonstrates a significant transcriptome difference between stroke-associated and asymptomatic CPs. Follow-up studies on the identified genes are needed to define whether they could be used as biomarkers of symptomatic CPs or have a role in plaque destabilization

Effects and feasibility of a standardised orientation and mobility training in using an identification cane for older adults with low vision: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Orientation and mobility training (O&M-training) in using an identification cane, also called symbol cane, is provided to people with low vision to facilitate independent participation in the community. In The Netherlands this training is mainly practice-based because a standardised and validly evaluated O&M-training in using the identification cane is lacking. Recently a standardised O&M-training in using the identification cane was developed. This training consists of two face-to-face sessions and one telephone session during which, in addition to usual care, the client's needs regarding mobility are prioritised, and cognitive restructuring techniques, action planning and contracting are applied to facilitate the use of the cane. This paper presents the design of a randomised controlled trial aimed to evaluate this standardised O&M-training in using the identification cane in older adults with low vision.</p> <p>Methods/design</p> <p>A parallel group randomised controlled trial was designed to compare the standardised O&M-training with usual care, i.e. the O&M-training commonly provided by the mobility trainer. Community-dwelling older people who ask for support at a rehabilitation centre for people with visual impairment and who are likely to receive an O&M-training in using the identification cane are included in the trial (N = 190). The primary outcomes of the effect evaluation are ADL self care and visual functioning with respect to distance activities and mobility. Secondary outcomes include quality of life, feelings of anxiety, symptoms of depression, fear of falling, and falls history. Data for the effect evaluation are collected by means of telephone interviews at baseline, and at 5 and 17 weeks after the start of the O&M-training. In addition to an effect evaluation, a process evaluation to study the feasibility of the O&M-training is carried out.</p> <p>Discussion</p> <p>The screening procedure for eligible participants started in November 2007 and will continue until October 2009. Preliminary findings regarding the evaluation are expected in the course of 2010. If the standardised O&M-training is more effective than the current O&M-training or, in case of equal effectiveness, is considered more feasible, the training will be embedded in the Dutch national instruction for mobility trainers.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00946062</p

The Role of Perfusion Computed Tomography in the Prediction of Cerebral Hyperperfusion Syndrome

Hyperperfusion syndrome (HPS) following carotid angioplasty with stenting (CAS) is associated with significant morbidity and mortality. At present, there are no reliable parameters to predict HPS. The aim of this study was to clarify whether perfusion computed tomography (CT) is a feasible and reliable tool in predicting HPS after CAS.We performed a retrospective case-control study of 54 patients (11 HPS patients and 43 non-HPS) with unilateral severe stenosis of the carotid artery who underwent CAS. We compared the prevalence of vascular risk factors and perfusion CT parameters including regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and time to peak (TTP) within seven days prior to CAS. Demographic information, risk factors for atherosclerosis, and perfusion CT parameters were evaluated by multivariable logistic regression analysis. The rCBV index was calculated as [(ipsilateral rCBV - contralateral rCBV)/contralateral rCBV], and indices of rCBF and TTP were similarly calculated. We found that eleven patients had HPS, including five with intracranial hemorrhages (ICHs) of whom three died. After a comparison with non-HPS control subjects, independent predictors of HPS included the severity of ipsilateral carotid artery stenosis, 3-hour mean systolic blood pressure (3 h SBP) after CAS, pre-stenting rCBV index >0.15 and TTP index >0.22.The combination of severe ipsilateral carotid stenosis, 3 h SBP after CAS, rCBV index and TTP index provides a potential screening tool for predicting HPS in patients with unilateral carotid stenosis receiving CAS. In addition, adequate management of post-stenting blood pressure is the most important treatable factor in preventing HPS in these high risk patients

Certification of breast centres in Germany: proof of concept for a prototypical example of quality assurance in multidisciplinary cancer care

<p>Abstract</p> <p>Background</p> <p>The main study objectives were: to develop a set of requirements of comprehensive breast centres; to establish a nationwide voluntary certification programme for breast centres based on such requirements, a certified quality management system (QMS), and scheduled independent, external audits and periodic recertification; and to demonstrate the general acceptance of such a certification programme with a view to introducing similar certification programmes for other major cancers.</p> <p>Methods</p> <p>Breast centres introduced a QMS and voluntarily participated in an external certification procedure based on guideline-derived Requirements of Breast Centres specifically developed for the application procedure, all subsequent audits and recertification. All data (numbers of pending and successful applications, sites/centre, etc.) were collected by a newly founded, independent organisation for certification of cancer services delivery. Data analysis was descriptive.</p> <p>Results</p> <p>Requirements of Breast Centres were developed by the German Cancer Society (DKG), the German Society of Senology (DGS) and other relevant specialist medical societies in the form of a questionnaire comprising 185 essential items based on evidence-based guidelines and the European Society of Breast Cancer Specialists' (EUSOMA) requirements of specialist breast units. From late 2002 to mid 2008, the number of participating breast centres rose from 1 to 175. As of mid 2008, 77% of an estimated 50,000 new breast cancers in Germany were diagnosed and treated at certified breast centres, 78% of which were single-site centres.</p> <p>Conclusion</p> <p>Nationwide voluntary certification of breast centres is feasible and well accepted in Germany. Dual certification of breast centres that involves certification of breast services to guideline-derived requirements in conjunction with independent certification of a mandatory QMS can serve as a model for other multidisciplinary site-specific cancer centres.</p

Multivariate Protein Signatures of Pre-Clinical Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Plasma Proteome Dataset

Background: Recent Alzheimer's disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. Methods and Findings: We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10−13). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. Conclusions: Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of plasma biomarkers for pre-clinical AD. While studies of independent test sets are required to validate the signatures, these analyses provide a starting point for developing a cost-effective and minimally invasive test capable of diagnosing AD in its pre-clinical stages