10 research outputs found
Spatial Learning and Action Planning in a Prefrontal Cortical Network Model
The interplay between hippocampus and prefrontal cortex (PFC) is fundamental to
spatial cognition. Complementing hippocampal place coding, prefrontal
representations provide more abstract and hierarchically organized memories
suitable for decision making. We model a prefrontal network mediating
distributed information processing for spatial learning and action planning.
Specific connectivity and synaptic adaptation principles shape the recurrent
dynamics of the network arranged in cortical minicolumns. We show how the PFC
columnar organization is suitable for learning sparse topological-metrical
representations from redundant hippocampal inputs. The recurrent nature of the
network supports multilevel spatial processing, allowing structural features of
the environment to be encoded. An activation diffusion mechanism spreads the
neural activity through the column population leading to trajectory planning.
The model provides a functional framework for interpreting the activity of PFC
neurons recorded during navigation tasks. We illustrate the link from single
unit activity to behavioral responses. The results suggest plausible neural
mechanisms subserving the cognitive “insight” capability originally
attributed to rodents by Tolman & Honzik. Our time course analysis of neural
responses shows how the interaction between hippocampus and PFC can yield the
encoding of manifold information pertinent to spatial planning, including
prospective coding and distance-to-goal correlates
WSES guidelines for management of Clostridium difficile infection in surgical patients
In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe
Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus
Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P-combined = 4.09 x 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P-combined = 2.74 x 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus
Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus
Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined = 4.09 × 10−9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13–1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined = 2.74 × 10−10; OR = 1.14, 95% CI = 1.10–1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus