Similar or Different? The Role of the Ventrolateral Prefrontal Cortex in Similarity Detection

Patients with frontal lobe syndrome can exhibit two types of abnormal behaviour when asked to place a banana and an orange in a single category: some patients categorize them at a concrete level (e.g., “both have peel”), while others continue to look for differences between these objects (e.g., “one is yellow, the other is orange”). These observations raise the question of whether abstraction and similarity detection are distinct processes involved in abstract categorization, and that depend on separate areas of the prefrontal cortex (PFC). We designed an original experimental paradigm for a functional magnetic resonance imaging (fMRI) study involving healthy subjects, confirming the existence of two distinct processes relying on different prefrontal areas, and thus explaining the behavioural dissociation in frontal lesion patients. We showed that: 1) Similarity detection involves the anterior ventrolateral PFC bilaterally with a right-left asymmetry: the right anterior ventrolateral PFC is only engaged in detecting physical similarities; 2) Abstraction per se activates the left dorsolateral PFC

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Obstetric and perinatal factors as predictors of child behaviour at 5 years

Objective To identify whether obstetric and perinatal factors are independent predictors of child behaviour at 5 years. Methodology The Mater University Study of Pregnancy (MUSP) is a prospective cohort study of 8556 mothers enrolled in early pregnancy. The relationship of obstetric and perinatal factors, maternal lifestyle, age and gender of the child, and social disadvantage were examined as predictors of child behaviour in 5005 children completing a modified child behaviour checklist at 5 years. This checklist contained three independent groups of behaviour: externalizng, internalizing and SAT (social, attentional and thought problems). Results In the initial analysis a limited number of associations were present. After adjusting for measures of social disadvantage, only number of antenatal admissions was associated with child behaviour in all three scales, while maternal cigarette smoking in pregnancy and male gender were associated with externalising and SAT behaviours. Conclusions Most common epidemiologic obstetric and perinatal risk factors were not independent predictors of behaviour problems in children at 5 years

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study

<p>Abstract</p> <p>Background</p> <p>To better characterize the value of cerebrospinal fluid (CSF) proteins as diagnostic markers in a clinical population of subacute encephalopathy patients with relatively low prevalence of sporadic Creutzfeldt-Jakob disease (sCJD), we studied the diagnostic accuracies of several such markers (14-3-3, tau and S100B) in 1000 prospectively and sequentially recruited Canadian patients with clinically suspected sCJD.</p> <p>Methods</p> <p>The study included 127 patients with autopsy-confirmed sCJD (prevalence = 12.7%) and 873 with probable non-CJD diagnoses. Standard statistical measures of diagnostic accuracy were employed, including sensitivity (Se), specificity (Sp), predictive values (PVs), likelihood ratios (LRs), and Receiver Operating Characteristic (ROC) analysis.</p> <p>Results</p> <p>At optimal cutoff thresholds (empirically selected for 14-3-3, assayed by immunoblot; 976 pg/mL for tau and 2.5 ng/mL for S100B, both assayed by ELISA), Se and Sp respectively were 0.88 (95% CI, 0.81-0.93) and 0.72 (0.69-0.75) for 14-3-3; 0.91 (0.84-0.95) and 0.88 (0.85-0.90) for tau; and 0.87 (0.80-0.92) and 0.87 (0.84-0.89) for S100B. The observed differences in Sp between 14-3-3 and either of the other 2 markers were statistically significant. Positive LRs were 3.1 (2.8-3.6) for 14-3-3; 7.4 (6.9-7.8) for tau; and 6.6 (6.1-7.1) for S100B. Negative LRs were 0.16 (0.10-0.26) for 14-3-3; 0.10 (0.06-0.20) for tau; and 0.15 (0.09-0.20) for S100B. Estimates of areas under ROC curves were 0.947 (0.931-0.961) for tau and 0.908 (0.888-0.926) for S100B. Use of interval LRs (iLRs) significantly enhanced accuracy for patient subsets [<it>e.g</it>., 41/120 (34.2%) of tested sCJD patients displayed tau levels > 10,000 pg/mL, with an iLR of 56.4 (22.8-140.0)], as did combining tau and S100B [<it>e.g</it>., for tau > 976 pg/mL and S100B > 2.5 ng/mL, positive LR = 18.0 (12.9-25.0) and negative LR = 0.02 (0.01-0.09)].</p> <p>Conclusions</p> <p>CSF 14-3-3, tau and S100B proteins are useful diagnostic markers of sCJD even in a low-prevalence clinical population. CSF tau showed better overall diagnostic accuracy than 14-3-3 or S100B. Reporting of quantitative assay results and combining tau with S100B could enhance case definitions used in diagnosis and surveillance of sCJD.</p

The potential monetary benefits of reclaiming hazardous waste sites in the Campania region: an economic evaluation

BACKGROUND: Evaluating the economic benefit of reducing negative health outcomes resulting from waste management is of pivotal importance for designing an effective waste policy that takes into account the health consequences for the populations exposed to environmental hazards. Despite the high level of Italian and international media interest in the problem of hazardous waste in Campania little has been done to reclaim the land and the waterways contaminated by hazardous waste. OBJECTIVE: This study aims to reduce the uncertainty about health damage due to waste exposure by providing for the first time a monetary valuation of health benefits arising from the reclamation of hazardous waste dumps in Campania. METHODS: First the criteria by which the landfills in the Campania region, in particular in the two provinces of Naples and Caserta, have been classified are described. Then, the annual cases of premature death and fatal cases of cancers attributable to waste exposure are quantified. Finally, the present value of the health benefits from the reclamation of polluted land is estimated for each of the health outcomes (premature mortality, fatal cancer and premature mortality adjusted for the cancer premium). Due to the uncertainty about the time frame of the benefits arising from reclamation, the latency of the effects of toxic waste on human health and the lack of context specific estimates of the Value of Preventing a Fatality (VPF), extensive sensitivity analyses are performed. RESULTS: There are estimated to be 848 cases of premature mortality and 403 cases of fatal cancer per year as a consequence of exposure to toxic waste. The present value of the benefit of reducing the number of waste associated deaths after adjusting for a cancer premium is euro11.6 billion. This value ranges from euro5.4 to euro20.0 billion assuming a time frame for benefits of 10 and 50 years respectively. CONCLUSION: This study suggests that there is a strong economic argument for both reclaiming the land contaminated with hazardous waste in the two provinces of Naples and Caserta and increasing the control of the territory in order to avoid the creation of new illegal dump sites

Left−Right Asymmetry Defect in the Hippocampal Circuitry Impairs Spatial Learning and Working Memory in iv Mice

Although left-right (L−R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv) mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness) in the synaptic distribution of theε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L−R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory

Molecular basis of structure and function of the microvillus membrane of intestinal epithelial cells

Correlation of molecular structure with biochemical functions of the plasma membrane of the microvilli of intestinal epithelial cells has been investigated by biochemical and electron microscopic procedures. Repeating particles, measuring approximately 60 &#197;in diameter, were found on the surface of the microvilli membrane which had been isolated or purified from rabbit intestinal epithelial cells and negatively stained with phosphotungstic acid. These particles were proved to be inherent components of the microvillus membrane, attached to the outer surface of its trilaminar structure, and were designated as the elementary particles of the microvilli of intestinal epithelial cells. Biochemical and electron microscopic identification of these elementary particles has been carried out by isolation of the elementary particles with papain from the isolated microvillus membrane, followed by purification of the particles by chromatographies on DEAE-cellulose and Sephadex columns. The partially purified particles containing invertase and leucine aminopeptidase are similar in size and structure to those of the elementary particles in the microvillus membrane. Evidence indicates that each of the elementary particles coincide with or include an enzyme molecule such as disaccharidase or peptidase, which carry out the terminal hydrolytic digestion of carbohydrates and proteins, respectively, on the surface of the microvillus membrane. Magnesium ionactivated adenosine triphosphatase and alkaline phosphatase cannot be solubilized with papain but remains in the smooth-surface membrane after the elementary particles have been removed. Cytochemical electron microscopic observation revealed that the active site of magnesium ion-activated adenosine triphosphatase is localized predominantly in the inner surface of the trilaminar structure of the microvillus membrane.</p

Comparison of Bayesian and frequentist approaches in modelling risk of preterm birth near the Sydney Tar Ponds, Nova Scotia, Canada

<p>Abstract</p> <p>Background</p> <p>This study compares the Bayesian and frequentist (non-Bayesian) approaches in the modelling of the association between the risk of preterm birth and maternal proximity to hazardous waste and pollution from the Sydney Tar Pond site in Nova Scotia, Canada.</p> <p>Methods</p> <p>The data includes 1604 observed cases of preterm birth out of a total population of 17559 at risk of preterm birth from 144 enumeration districts in the Cape Breton Regional Municipality. Other covariates include the distance from the Tar Pond; the rate of unemployment to population; the proportion of persons who are separated, divorced or widowed; the proportion of persons who have no high school diploma; the proportion of persons living alone; the proportion of single parent families and average income. Bayesian hierarchical Poisson regression, quasi-likelihood Poisson regression and weighted linear regression models were fitted to the data.</p> <p>Results</p> <p>The results of the analyses were compared together with their limitations.</p> <p>Conclusion</p> <p>The results of the weighted linear regression and the quasi-likelihood Poisson regression agrees with the result from the Bayesian hierarchical modelling which incorporates the spatial effects.</p

Rapid automatized naming as an index of genetic liability to autism

This study investigated rapid automatized naming (RAN) ability in high functioning individuals with autism and parents of individuals with autism. Findings revealed parallel patterns of performance in parents and individuals with autism, where both groups had longer naming times than controls. Significant parent-child correlations were also detected, along with associations with language and personality features of the broad autism phenotype (retrospective reports of early language delay, socially reticent personality). Together, findings point towards RAN as a potential marker of genetic liability to autism