Skull Modeling Effects in Conductivity Estimates Using Parametric Electrical Impedance Tomography.

OBJECTIVE: To estimate scalp, skull, compact bone, and marrow bone electrical conductivity values based on electrical impedance tomography (EIT) measurements, and to determine the influence of skull modeling details on the estimates. METHODS: We collected EIT data with 62 current injection pairs and built five 6-8 million finite element (FE) head models with different grades of skull simplifications for four subjects, including three whose head models serve as Atlases in the scientific literature and in commercial equipment (Colin27 and EGI's Geosource atlases). We estimated electrical conductivity of the scalp, skull, marrow bone, and compact bone tissues for each current injection pair, each model, and each subject. RESULTS: Closure of skull holes in FE models, use of simplified four-layer boundary element method-like models, and neglecting the CSF layer produce an overestimation of the skull conductivity of 10%, 10%-20%, and 20%-30%, respectively (accumulated overestimation of 50%-70%). The average extracted conductivities are 288 ± 53 (the scalp), 4.3 ± 0.08 (the compact bone), and 5.5 ± 1.25 (the whole skull) mS/m. The marrow bone estimates showed large dispersion. CONCLUSION: Present EIT estimates for the skull conductivity are lower than typical literature reference values, but previous in vivo EIT results are likely overestimated due to the use of simpler models. SIGNIFICANCE: Typical literature values of 7-10 mS/m for skull conductivity should be replaced by the present estimated values when using detailed skull head models. We also provide subject specific conductivity estimates for widely used Atlas head models.

Rhegmatogenous retinal detachment following intravitreal ocriplasmin.

PURPOSE: To describe the characteristics and outcomes of patients presenting with rhegmatogenous retinal detachment (RRD) after ocriplasmin (OCP) injection. METHODS: Retrospective, multi-centre, observational case series with case note review. RESULTS: Eight patients with symptomatic vitreomacular traction (six with concomitant macular hole) were diagnosed with RRD after a median of 16 days (range 3-131 days) post-OCP injection. Presentation was within 3 weeks of the OCP injection in six of the cases. Five patients presented with symptoms post-OCP, and three were diagnosed asymptomatically on planned visits. Seven cases were phakic, one had high myopia (>8 dioptres), and two cases had lattice degeneration. Following RRD surgery, hole closure was achieved in 5/6 MH cases. The final median BCVA at 7 months was 20/80 (range 20/40-20/1200) similar to the baseline BCVA 20/80, with four patients gaining ≥1 line of vision compared to baseline but three losing ≥3 lines. CONCLUSIONS: RRD is a non-negligible risk associated with intravitreal OCP, and it should be used with caution in eyes with high myopia and peripheral retinal pathology predisposing to RRD. Detailed peripheral retinal examination is recommended pre- and postoperatively at all visits. Patients should be advised to seek attention if symptoms recur after initial presentation.

Impact of high-intensity interval duration on perceived exertion.

PURPOSE: RPE is increasingly being considered as a viable tool beyond its original use for monitoring in-task exercise intensity. Research indicates that anticipated, in-task, and postexercise RPE values are often notably different from one another. An important new consideration is how perceptions are impacted by high-intensity interval training (HIT). This study aims to compare RPE responses before, during, and after continuous and HIT exercise trials. METHODS: Twenty (11 females and 9 males; mean ± SD age, 22 ± 4 yr) overweight (mean ± SD body mass index, 29 ± 3 kg·m(-2)) and unfit (mean ± SD V˙O2peak, 28 ± 5 mL·kg·min(-1)) participants completed a 20-min heavy continuous (HC) trial and three 24-min severe-intensity interval trials that utilized 1:1 work-to-recovery ratios: 30 s (Severe Interval-30), 60 s (Severe Interval-60), and 120 s (Severe Interval-120). Exertion was assessed using the Borg CR10 Scale. Data were analyzed using repeated-measures ANOVA and pairwise comparisons. RESULTS: Anticipated exertion was highest in the Severe Interval-120 trial (5.8 ± 2.0; P < 0.05) compared with other trials. Exertion increased from beginning to end in all trials (P < 0.05), with the greatest increases observed within the HC trial. Session RPE for the Severe Interval-120 trial (6.4 ± 2.3) was higher than those for all other trials (P < 0.05), and session RPE for the Severe Interval-30 trial (3.7 ± 1.8) was lower than that for the HC trial (4.9 ± 1.6; P < 0.05). CONCLUSIONS: These findings suggest that 30-s HIT protocols limit the perceptual drift that occurs during exercise, in comparison to HC exercise. Moreover, performing more intervals of shorter durations appears to produce lower postexercise RPE values than performing fewer intervals of longer duration and equal intensity. Because effort perception may influence behavior, these results could have implications for the prescription of interval training in overweight sedentary adults.

Global QSAR models of skin sensitisers for regulatory purposes.

BACKGROUND: The new European Regulation on chemical safety, REACH, (Registration, Evaluation, Authorisation and Restriction of CHemical substances), is in the process of being implemented. Many chemicals used in industry require additional testing to comply with the REACH regulations. At the same time EU member states are attempting to reduce the number of animals used in experiments under the 3 Rs policy, (refining, reducing, and replacing the use of animals in laboratory procedures). Computational techniques such as QSAR have the potential to offer an alternative for generating REACH data. The FP6 project CAESAR was aimed at developing QSAR models for 5 key toxicological endpoints of which skin sensitisation was one. RESULTS: This paper reports the development of two global QSAR models using two different computational approaches, which contribute to the hybrid model freely available online. CONCLUSIONS: The QSAR models for assessing skin sensitisation have been developed and tested under stringent quality criteria to fulfil the principles laid down by the OECD. The final models, accessible from CAESAR website, offer a robust and reliable method of assessing skin sensitisation for regulatory use.

Management of cellulitis after insect bites.

Emergency nurses must be able to manage patients with undifferentiated and previously undiagnosed conditions. Cellulitis, for example, is often seen in emergency departments and must be assessed correctly to ensure early treatment and reduce patients' risk of developing systemic sepsis. This article uses a case study to describe the assessment and management, including examination techniques, of a patient admitted to the ED with cellulitis after an insect bite,

Multifaceted implementation of stroke prevention guidelines in primary care: cluster-randomised evaluation of clinical and cost effectiveness.

OBJECTIVE: To evaluate clinical and cost effectiveness of implementing evidence-based guidelines for the prevention of stroke. DESIGN: Cluster-randomised trial SETTING: Three primary care organisations in the North of England covering a population of 400,000. PARTICIPANTS: Seventy six primary care teams in four clusters: North, South & West, City I and City II. INTERVENTION: Guidelines for the management of patients with atrial fibrillation and transient ischaemic attack (TIA) were developed and implemented using a multifaceted approach including evidence-based recommendations, audit and feedback, interactive educational sessions, patient prompts and outreach visits. OUTCOMES: Identification and appropriate treatment of patients with atrial fibrillation or TIA, and cost effectiveness. RESULTS: Implementation led to 36% increase (95% CI 4% to 78%) in diagnosis of atrial fibrillation, and improved treatment of TIA (odds ratio of complying with guidelines 1.8; 95% CI 1.1 to 2.8). Combined analysis of atrial fibrillation and TIA estimates that compliance was significantly greater (OR 1.46 95% CI 1.10 to 1.94) in the condition for which practices had received the implementation programme. The development and implementation of guidelines cost less than 1500 pounds per practice. The estimated costs per quality-adjusted life year gained by patients with atrial fibrillation or TIA were both less than 2000 pounds, very much less than the usual criterion for cost effectiveness. CONCLUSIONS: Implementation of evidence-based guidelines improved the quality of primary care for atrial fibrillation and TIA. The intervention was feasible and very cost effective. Key components of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication and use of established networks and opinion leaders.

Opacification of the Hydroview H60M intraocular lens: total patient recall.

PURPOSE: To report the prevalence of intraocular lens (IOL) opacification and related clinical features in patients implanted with Hydroview IOL. SETTING: Gloucestershire Eye Unit, Gloucestershire, United Kingdom. METHODS: A total of 1330 eyes of 1265 patients who had cataract surgery with Hydroview IOL implantation between September 2000 and April 2001 were reviewed between April and October 2004. The visual acuity, visual symptoms, IOL status, and associated ocular comorbidity were recorded. RESULTS: One hundred ninety-three (14.5%) of 1330 eyes had evidence of IOL opacification. A total of 56 (4.2%) had visually significant opacification and had IOL exchange. The prevalence of IOL opacification ranged from 1.1% in patients who had surgery in September 2000 to 36.3% in the December 2000 group. In eyes with IOL opacification, the visual symptoms were decreased vision (57%), glare (32%), and mistiness of vision (27%). One hundred forty-four eyes (75%) with IOL opacification had visual acuity of 6/12 or better; 21.5% of diabetic eyes had IOL opacification compared with 14.3% of nondiabetic eyes (P =.06); 20.5% of glaucomatous eyes had IOL opacification compared with 14.0% of nonglaucomatous eyes (P = .033). CONCLUSIONS: This is the first large sample recall of patients implanted with the Hydroview H60M IOL. The overall prevalence of IOL opacification was 14.5%, with peak prevalence in patients who had surgery in December 2000.

Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk.

OBJECTIVES: We sought to investigate the effects of sleep loss on high-sensitivity C-reactive protein (CRP) levels. BACKGROUND: Concentrations of high-sensitivity CRP are predictive of future cardiovascular morbidity. In epidemiologic studies, short sleep duration and sleep complaints have also been associated with increased cardiovascular morbidity. Two studies were undertaken to examine the effect of acute total and short-term partial sleep deprivation on concentrations of high-sensitivity CRP in healthy human subjects. METHODS: In Experiment 1, 10 healthy adult subjects stayed awake for 88 continuous hours. Samples of high-sensitivity CRP were collected every 90 min for 5 consecutive days, encompassing the vigil. In Experiment 2, 10 subjects were randomly assigned to either 8.2 h (control) or 4.2 h (partial sleep deprivation) of nighttime sleep for 10 consecutive days. Hourly samples of high-sensitivity CRP were taken during a baseline night and on day 10 of the study protocol. RESULTS: The CRP concentrations increased during both total and partial sleep deprivation conditions, but remained stable in the control condition. Systolic blood pressure increased across deprivation in Experiment 1, and heart rate increased in Experiment 2. CONCLUSIONS: Both acute total and short-term partial sleep deprivation resulted in elevated high-sensitivity CRP concentrations, a stable marker of inflammation that has been shown to be predictive of cardiovascular morbidity. We propose that sleep loss may be one of the ways that inflammatory processes are activated and contribute to the association of sleep complaints, short sleep duration, and cardiovascular morbidity observed in epidemiologic surveys.

Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change.

Protein kinase B (PKB/Akt) is a key regulator of cell growth, proliferation and metabolism. It possesses an N-terminal pleckstrin homology (PH) domain that interacts with equal affinity with the second messengers PtdIns(3,4,5)P3 and PtdIns(3,4)P2, generated through insulin and growth factor-mediated activation of phosphoinositide 3-kinase (PI3K). The binding of PKB to PtdIns(3,4,5)P3/PtdIns(3,4)P2 recruits PKB from the cytosol to the plasma membrane and is also thought to induce a conformational change that converts PKB into a substrate that can be activated by the phosphoinositide-dependent kinase 1 (PDK1). In this study we describe two high-resolution crystal structures of the PH domain of PKBalpha in a noncomplexed form and compare this to a new atomic resolution (0.98 A, where 1 A=0.1 nm) structure of the PH domain of PKBalpha complexed to Ins(1,3,4,5)P4, the head group of PtdIns(3,4,5)P3. Remarkably, in contrast to all other PH domains crystallized so far, our data suggest that binding of Ins(1,3,4,5)P4 to the PH domain of PKB, induces a large conformational change. This is characterized by marked changes in certain residues making up the phosphoinositide-binding site, formation of a short a-helix in variable loop 2, and a movement of variable loop 3 away from the lipid-binding site. Solution studies with CD also provided evidence of conformational changes taking place upon binding of Ins(1,3,4,5)P4 to the PH domain of PKB. Our data provides the first structural insight into the mechanism by which the interaction of PKB with PtdIns(3,4,5)P3/PtdIns(3,4)P2 induces conformational changes that could enable PKB to be activated by PDK1.