Multiple Effects of Prefrontal Lesions on Task-Switching

This study examined the performance of 41 patients with focal prefrontal cortical lesions and 38 healthy controls on a task-switching procedure. Three different conditions were evaluated: single tasks without switches and two switching tasks with the currently relevant task signalled either 1500 ms (Long Cue) or 200 ms (Short Cue) before the stimulus. Patients with Superior Medial lesions showed both a general slowing of reaction time (RT) and a significantly increased switch cost as measured by RT. No other prefrontal group showed this increased reaction time switch cost. Increased error rates in the switching conditions, on the other hand, were observed in patients with Inferior Medial lesions and, to a lesser extent, ones with Superior Medial lesions. Patients with left dorsolateral lesions (9/46v) showed slower learning of the task as indicated by a high error rate early on. Several different processes are involved in task-switching and these are selectively disrupted by lesions to specific areas of the frontal lobes

Modelling and simulation of a stationary high-rise elevator system to predict the dynamic interactions between its components

In a high-rise elevator system lateral vibrations of the suspension and compensating ropes, coupled with vertical motions of the car and counterweight are induced by the building structure motions. When the frequency of the building coincides with the fundamental natural frequency of the ropes, large resonance whirling motions of the ropes result. This phenomenon leads to impacts of the ropes on the elevator walls, large displacements of the car and counterweight making the building and elevator system unsafe. This paper presents a comprehensive mathematical model of a high-rise elevator system taking into account the combined lateral stiffness of the roller guides and guide rails. The results and analysis presented in the paper demonstrate frequency curve veering phenomena and a wide range of resonances that occur in the system. A case study is presented when the car is parked at a landing level where the fundamental natural frequencies of the car, suspension and compensating rope system coincide with one of the natural frequencies of the high-rise building. The results show a range of nonlinear dynamic interactions between the components of the elevator system that play a significant role in the operation of the entire installation

No Evidence That Gratitude Enhances Neural Performance Monitoring or Conflict-Driven Control

It has recently been suggested that gratitude can benefit self-regulation by reducing impulsivity during economic decision making. We tested if comparable benefits of gratitude are observed for neural performance monitoring and conflict-driven self-control. In a pre-post design, 61 participants were randomly assigned to either a gratitude or happiness condition, and then performed a pre-induction flanker task. Subsequently, participants recalled an autobiographical event where they had felt grateful or happy, followed by a post-induction flanker task. Despite closely following existing protocols, participants in the gratitude condition did not report elevated gratefulness compared to the happy group. In regard to self-control, we found no association between gratitude--operationalized by experimental condition or as a continuous predictor--and any control metric, including flanker interference, post-error adjustments, or neural monitoring (the error-related negativity, ERN). Thus, while gratitude might increase economic patience, such benefits may not generalize to conflict-driven control processes

Effects of noise exposure on young adults with normal audiograms II: Behavioral measures

An estimate of lifetime noise exposure was used as the primary predictor of performance on a range of behavioral tasks: frequency and intensity difference limens, amplitude modulation detection, interaural phase discrimination, the digit triplet speech test, the co-ordinate response speech measure, an auditory localization task, a musical consonance task and a subjective report of hearing ability. One hundred and thirty-eight participants (81 females) aged 18–36 years were tested, with a wide range of self-reported noise exposure. All had normal pure-tone audiograms up to 8 kHz. It was predicted that increased lifetime noise exposure, which we assume to be concordant with noise-induced cochlear synaptopathy, would elevate behavioral thresholds, in particular for stimuli with high levels in a high spectral region. However, the results showed little effect of noise exposure on performance. There were a number of weak relations with noise exposure across the test battery, although many of these were in the opposite direction to the predictions, and none were statistically significant after correction for multiple comparisons. There were also no strong correlations between electrophysiological measures of synaptopathy published previously and the behavioral measures reported here. Consistent with our previous electrophysiological results, the present results provide no evidence that noise exposure is related to significant perceptual deficits in young listeners with normal audiometric hearing. It is possible that the effects of noise-induced cochlear synaptopathy are only measurable in humans with extreme noise exposures, and that these effects always co-occur with a loss of audiometric sensitivity

An investigation of EPO as a tissue protective agent in human kidney transplantation

Ischaemia-reperfusion injury (IRI) has been identified as a major contributor to both short and long term kidney transplant failure. Experimental evidence from the literature suggests that Erythropoietin (EPO) is tissue protective, reducing both inflammation and apoptosis following IRI. We performed a randomised, double blind, placebo controlled trial examining the tissue protective effect of high dose EPO (100,000iu over 3 days) in 39 recipients of an extended criteria donor kidney or a non-heart-beating donor kidney. The primary endpoints of the study were difference in plasma and urinary biomarker levels (NGAL, IL-18 and KIM-1) in addition to changes in gene expression. Secondary endpoints included safety, clinical data and differences in metabolomics profiles. There was no difference detected between the treatment groups in terms of biomarkers, gene expression, metabolomics profiling or clinical parameters. No adverse events related to EPO therapy were recorded. In addition, we developed a cell model of kidney transplantation using primary tubulo-epithelial cells and HMEC-1 cells, with which to confirm the protective effects of EPO. Treatment with 50U/ml one hour prior to undergoing cold hypoxia resulted in the maximum degree of tissue protection, as measured using an MTT and an LDH assay. No evidence of EPO toxicity was demonstrated. Tubulo-epithelial cells expressed EPOR mRNA and protein. No CD131 receptor could be demonstrated. In summary, EPO confers tissue protection in a cell model of kidney transplantation but this has not been shown to occur in a clinical trial using high dose EPO in recipients of marginal donor kidneys.EThOS - Electronic Theses Online ServiceDepartment of Renal Medicine, Manchester Royal InfirmaryGBUnited Kingdo

Reconstruction of Family-Level Phylogenetic Relationships within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes

Background: Demosponges are challenging for phylogenetic systematics because of their plastic and relatively simple morphologies and many deep divergences between major clades. To improve understanding of the phylogenetic relationships within Demospongiae, we sequenced and analyzed seven nuclear housekeeping genes involved in a variety of cellular functions from a diverse group of sponges. Methodology/Principal Findings: We generated data from each of the four sponge classes (i.e., Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha), but focused on family-level relationships within demosponges. With data for 21 newly sampled families, our Maximum Likelihood and Bayesian-based approaches recovered previously phylogenetically defined taxa: Keratosap, Myxospongiaep, Spongillidap, Haploscleromorphap (the marine haplosclerids) and Democlaviap. We found conflicting results concerning the relationships of Keratosap and Myxospongiaep to the remaining demosponges, but our results strongly supported a clade of Haploscleromorphap+Spongillidap+Democlaviap. In contrast to hypotheses based on mitochondrial genome and ribosomal data, nuclear housekeeping gene data suggested that freshwater sponges (Spongillidap) are sister to Haploscleromorphap rather than part of Democlaviap. Within Keratosap, we found equivocal results as to the monophyly of Dictyoceratida. Within Myxospongiaep, Chondrosida and Verongida were monophyletic. A well supported clade within Democlaviap, Tetractinellidap, composed of all sampled members of Astrophorina and Spirophorina (including the only lithistid in our analysis), was consistently revealed as the sister group to all other members of Democlaviap. Within Tetractinellidap, we did not recover monophyletic Astrophorina or Spirophorina. Our results also reaffirmed the monophyly of order Poecilosclerida (excluding Desmacellidae and Raspailiidae), and polyphyly of Hadromerida and Halichondrida. Conclusions/Significance: These results, using an independent nuclear gene set, confirmed many hypotheses based on ribosomal and/or mitochondrial genes, and they also identified clades with low statistical support or clades that conflicted with traditional morphological classification. Our results will serve as a basis for future exploration of these outstanding questions using more taxon- and gene-rich datasets

Epidemiology of posttransplantation lymphoproliferative disorder in adult renal transplant recipients.

Background. There is little information in the literature describing the relationship between posttransplantation lym- phoproliferative disorder (PTLD) incidence and presentation with both recipient Epstein-Barr virus (EBV) serostatus and EBV status of PTLD histology, particularly in the late posttransplantation period. Methods. This study reports the largestUK single-center, single-organ analysis of PTLD to date in a retrospective cohort study of 80 cases occurring in 4189 adult renal transplant recipients. Results. The incidence rate was 2.6 cases per 1000 patient-years (95%confidence interval [95% CI], 2.1Y3.2) for PTLD, 1.8 (95% CI, 1.4Y2.4) for non-Hodgkin’s lymphoma, and 0.2 (95% CI, 0.07Y4.2) for Hodgkin’s lymphoma. Non- Hodgkin’s lymphoma occurred at a rate 7.6 times that of the adult general population in England, whereas the rate for Hodgkin’s lymphoma was 5.9 times. The incidence of PTLD was highest during the 10th to 14th posttransplantation years. Early-onset disease was associated with EBV-seronegative recipient status, EBV-positive histology, and the in- volvement of extranodal sites. PTLD occurring in EBV-seronegative recipients was associated with EBV nuclear antigen antibody deficiency, polymorphic disease, and the involvement of extranodal sites. EBV-negative histology occurred in 32%of cases at amedian time to presentation of 109months. PTLD involving the allograft, central nervous system, and skin was uncommon and occurred late. Conclusion. The incidence of PTLD is highest in the late posttransplantation period. Close clinical surveillance and education for transplant recipients is required for the duration of time while immunosuppressed. Failure to detect EBV DNA in blood should not reassure, particularly in patients with symptoms such as abdominal pain, oropharyngeal complaints, neck lumps, and B-symptoms

Distinct and dissociable EEG networks are associated with recovery of cognitive function following anesthesia-induced unconsciousness

The temporal trajectories and neural mechanisms of recovery of cognitive function after a major perturbation of consciousness is of both clinical and neuroscientific interest. The purpose of the present study was to investigate network-level changes in functional brain connectivity associated with the recovery and return of six cognitive functions after general anesthesia. High-density electroencephalograms (EEG) were recorded from healthy volunteers undergoing a clinically relevant anesthesia protocol (propofol induction and isoflurane maintenance), and age-matched healthy controls. A battery of cognitive tests (motor praxis, visual object learning test, fractal-2-back, abstract matching, psychomotor vigilance test, digital symbol substitution test) was administered at baseline, upon recovery of consciousness (ROC), and at half-hour intervals up to 3 h following ROC. EEG networks were derived using the strength of functional connectivity measured through the weighted phase lag index (wPLI). A partial least squares (PLS) analysis was conducted to assess changes in these networks: (1) between anesthesia and control groups; (2) during the 3-h recovery from anesthesia; and (3) for each cognitive test during recovery from anesthesia. Networks were maximally perturbed upon ROC but returned to baseline 30-60 min following ROC, despite deficits in cognitive performance that persisted up to 3 h following ROC. Additionally, during recovery from anesthesia, cognitive tests conducted at the same time-point activated distinct and dissociable functional connectivity networks across all frequency bands. The results highlight that the return of cognitive function after anesthetic-induced unconsciousness is task-specific, with unique behavioral and brain network trajectories of recovery