Temporally correlated fluctuations drive epileptiform dynamics

Published onlineJournal ArticleMacroscopic models of brain networks typically incorporate assumptions regarding the characteristics of afferent noise, which is used to represent input from distal brain regions or ongoing fluctuations in non-modelled parts of the brain. Such inputs are often modelled by Gaussian white noise which has a flat power spectrum. In contrast, macroscopic fluctuations in the brain typically follow a 1/f(b) spectrum. It is therefore important to understand the effect on brain dynamics of deviations from the assumption of white noise. In particular, we wish to understand the role that noise might play in eliciting aberrant rhythms in the epileptic brain. To address this question we study the response of a neural mass model to driving by stochastic, temporally correlated input. We characterise the model in terms of whether it generates "healthy" or "epileptiform" dynamics and observe which of these dynamics predominate under different choices of temporal correlation and amplitude of an Ornstein-Uhlenbeck process. We find that certain temporal correlations are prone to eliciting epileptiform dynamics, and that these correlations produce noise with maximal power in the δ and θ bands. Crucially, these are rhythms that are found to be enhanced prior to seizures in humans and animal models of epilepsy. In order to understand why these rhythms can generate epileptiform dynamics, we analyse the response of the model to sinusoidal driving and explain how the bifurcation structure of the model gives rise to these findings. Our results provide insight into how ongoing fluctuations in brain dynamics can facilitate the onset and propagation of epileptiform rhythms in brain networks. Furthermore, we highlight the need to combine large-scale models with noise of a variety of different types in order to understand brain (dys-)function.This work was supported by the European Commission through the FP7 Marie Curie Initial Training Network 289146 (NETT: Neural Engineering Transformative Technologies), by the Spanish Ministry of Economy and Competitiveness and FEDER (project FIS2012-37655-C02-01). J.G.O. also acknowledges support from the ICREA Academia programme, the Generalitat de Catalunya (project 2014SGR0947), and the “María de Maeztu” Programme for Units of Excellence in R&D (Spanish Ministry of Economy and Competitiveness, MDM-2014-0370) M.G. gratefully acknowledges the financial support of the EPSRC via grant EP/N014391/1. The contribution of M.G. was generously supported by a Wellcome Trust Institutional Strategic Support Award (WT105618MA)

Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (disc1) Mutant Zebrafish

Synthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (DISC1) is a gene with important roles in neurodevelopment that has been associated with psychiatric disorders in pedigree analyses. Using zebrafish as a model, we investigated (1) the behavioral impact of developmental exposure to 3 μM 1-pentyl-3-(1-naphthoyl)-indole (JWH-018; a common psychoactive synthetic cannabinoid) and (2) whether disc1 moderates the effects of JWH-018. As altered anxiety responses are seen in several psychiatric disorders, we focused on zebrafish anxiety-like behavior. Zebrafish embryos were exposed to JWH-018 from one to six days post-fertilization. Anxiety-like behavior was assessed using forced light/dark and acoustic startle assays in larvae and novel tank diving in adults. Compared to controls, both acutely and developmentally exposed zebrafish larvae had impaired locomotion during the forced light/dark test, but anxiety levels and response to startle stimuli were unaltered. Adult zebrafish developmentally exposed to JWH-018 spent less time on the bottom of the tank, suggesting decreased anxiety. Loss-of-function in disc1 increased anxiety-like behavior in the tank diving assay but did not alter sensitivity to JWH-018. Results suggest developmental exposure to JWH-018 has a long-term behavioral impact in zebrafish, which is not moderated by disc1

A mixed reality telepresence system for collaborative space operation

This paper presents a Mixed Reality system that results from the integration of a telepresence system and an application to improve collaborative space exploration. The system combines free viewpoint video with immersive projection technology to support non-verbal communication, including eye gaze, inter-personal distance and facial expression. Importantly, these can be interpreted together as people move around the simulation, maintaining natural social distance. The application is a simulation of Mars, within which the collaborators must come to agreement over, for example, where the Rover should land and go. The first contribution is the creation of a Mixed Reality system supporting contextualization of non-verbal communication. Tw technological contributions are prototyping a technique to subtract a person from a background that may contain physical objects and/or moving images, and a light weight texturing method for multi-view rendering which provides balance in terms of visual and temporal quality. A practical contribution is the demonstration of pragmatic approaches to sharing space between display systems of distinct levels of immersion. A research tool contribution is a system that allows comparison of conventional authored and video based reconstructed avatars, within an environment that encourages exploration and social interaction. Aspects of system quality, including the communication of facial expression and end-to-end latency are reported

Immediate implant placement in fresh alveolar sockets with a minimal split-thickness envelope flap: A randomised controlled clinical trial

OBJECTIVES: Comparing PES/WES scores, modified success rate, survival, success, buccal bone thickness and patient-reported outcomes of immediate dental implants placed in fresh alveolar sockets using a flap or a minimal split-thickness envelope flap (MSTEF). MATERIALS AND METHODS: Implants following random assignment into a flap or MSTEF group were placed immediately in anterior and premolar areas. Guided bone regeneration and autogenous connective tissue graft were used in all cases. A temporary prosthesis was provided followed by the final prosthesis at 16-18 weeks. Success and survival rates together with radiographic buccal bone thickness and patient satisfaction were evaluated at 12 months post-loading. The aesthetic outcome was evaluated through the Pink (PES) and White (WES) Aesthetic Score by 8 blind clinicians of different training background and incorporated in modified success criteria. RESULTS: 28 implants were placed on 28 patients. No statistically significant differences were noted in PES (10.54 control vs. 10.80 test), WES scores (6.97 control vs. 6.95 test) or success criteria including aesthetic parameters (modified success criteria) for the different specialty groups (Range 69%-92%). In addition, no statistically significant differences were noted in survival (100%), success (100%), buccal wall thickness between control (0.72 +/-0.22) and test group (0.92+/-0.31) and patients' reported outcomes. CONCLUSIONS: Immediate dental implant treatment with flap/ MSTEF provided similar mean PES/WES scores, modified success rate, survival, mean buccal bone levels and patients' satisfaction. However, aesthetic failures were common in both groups

Immediate implant placement in fresh alveolar sockets with a minimal split-thickness envelope flap. A randomised controlled clinical trial.

OBJECTIVES: Comparing PES/WES scores, modified success rate, survival, success, buccal bone thickness and patient-reported outcomes of immediate dental implants placed in fresh alveolar sockets using a flap or a minimal split-thickness envelope flap (MSTEF). MATERIALS AND METHODS: Implants following random assignment into a flap or MSTEF group were placed immediately in anterior and premolar areas. Guided bone regeneration and autogenous connective tissue graft were used in all cases. A temporary prosthesis was provided followed by the final prosthesis at 16-18 weeks. Success and survival rates together with radiographic buccal bone thickness and patient satisfaction were evaluated at 12 months post-loading. The aesthetic outcome was evaluated through the Pink (PES) and White (WES) Aesthetic Score by 8 blind clinicians of different training background and incorporated in modified success criteria. RESULTS: 28 implants were placed on 28 patients. No statistically significant differences were noted in PES (10.54 control vs. 10.80 test), WES scores (6.97 control vs. 6.95 test) or success criteria including aesthetic parameters (modified success criteria) for the different specialty groups (Range 69%-92%). In addition, no statistically significant differences were noted in survival (100%), success (100%), buccal wall thickness between control (0.72 +/-0.22) and test group (0.92+/-0.31) and patients' reported outcomes. CONCLUSIONS: Immediate dental implant treatment with flap/ MSTEF provided similar mean PES/WES scores, modified success rate, survival, mean buccal bone levels and patients' satisfaction. However, aesthetic failures were common in both groups

Early Trends in Cystatin C and Outcomes in Patients with Cirrhosis and Acute Kidney Injury

Background. Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35%) met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36%) (Scr−/CysC−); only cystatin increased 25 (24%) (Scr−/CysC+); only creatinine increased 15 (14%) (Scr+/CysC−); and both increased 28 (26%) (Scr+/CysC+). With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, and , respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes

Label-free detection of human prostate-specific antigen (hPSA) using film bulk acoustic resonators (FBARs)

Label-free detection of cancer biomarkers using low cost biosensors has promising applications in clinical diagnostics. In this work, ZnO-based thin film bulk acoustic wave resonators (FBARs) with resonant frequency of ∼1.5 GHz and mass sensitivity of 0.015 mg/m2 (1.5 ng/cm2) have been fabricated for their deployment as biosensors. Mouse monoclonal antibody, anti-human prostate-specific antigen (Anti-hPSA) has been used to bind human prostate-specific antigen (hPSA), a model cancer used in this study. Ellipsometry was used to characterize and optimise the antibody adsorption and antigen binding on gold surface. It was found that the best amount of antibody at the gold surface for effective antigen binding is around 1 mg/m2, above or below which resulted in the reduced antigen binding due to either the limited binding sites (below 1 mg/m2) or increased steric effect (above 1 mg/m2). The FBAR data were in good agreement with the data obtained from ellipsometry. Antigen binding experiments using FBAR sensors demonstrated that FBARs have the capability to precisely detect antigen binding, thereby making FBARs an attractive low cost alternative to existing cancer diagnostic sensors.This work was supported by the Engineering and Physical Sciences Research Council [grants EP/F062966/1, EP/F063865/1 and EP/F06294X/1], the Royal Society [grant RG120061] and the National Natural Science Foundation of China (NSFC) [grant 61150110485].This is the accepted manuscript version. The final published version of the article is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0925400513011052

Patients presenting with miliaria while wearing flame resistant clothing in high ambient temperatures: a case series

<p>Abstract</p> <p>Introduction</p> <p>Clothing can be a cause of occupational dermatitis. Frequent causes of clothing-related dermatological problems can be the fabric itself and/or chemical additives used in the laundering process, friction from certain fabrics excessively rubbing the skin, or heat retention from perspiration-soaked clothing in hot working environments. To the best of our knowledge, these are the first reported cases of miliaria rubra associated with prolonged use of flame resistant clothing in the medical literature.</p> <p>Case presentation</p> <p>We report 18 cases (14 men and 4 women, with an age range of 19 to 37 years) of moderate to severe skin irritation associated with wearing flame resistant clothing in hot arid environments (temperature range: 39 to 50°C, 5% to 25% relative humidity). We describe the medical history in detail of a 23-year-old Caucasian woman and a 31-year-old African-American man. A summary of the other 16 patients is also provided.</p> <p>Conclusions</p> <p>These cases illustrate the potential serious nature of miliaria with superimposed <it>Staphylococcus </it>infections. All 18 patients fully recovered with topical skin treatment and modifications to their dress ensemble. Clothing, in particular blend fabrics, must be thoroughly laundered to adequately remove detergent residue. While in hot environments, individuals with sensitive skin should take the necessary precautions such as regular changing of clothing and good personal hygiene to ensure that their skin remains as dry and clean as possible. It is also important that they report to their health care provider as soon as skin irritation or rash appears to initiate any necessary medical procedures. Miliaria rubra can take a week or longer to clear, so removal of exposure to certain fabric types may be necessary.</p