Associations between purine metabolites and clinical symptoms in schizophrenia

Background: The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology of schizophrenia. Methodology/Principal Findings: Breakdown products in purine pathway were measured using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system for 25 first-episode neuroleptic-naïve patients with schizophrenia at baseline and at 4-weeks following initiation of treatment with antipsychotic medication. Associations between these metabolites and clinical and neurological symptoms were examined at both time points. The ratio of uric acid and guanine measured at baseline predicted clinical improvement following four weeks of treatment with antipsychotic medication. Baseline levels of purine metabolites also predicted clinical and neurological symtpoms recorded at baseline; level of guanosine was associated with degree of clinical thought disturbance, and the ratio of xanthosine to guanosine at baseline predicted degree of impairment in the repetition and sequencing of actions. Conclusions/Significance: Findings suggest an association between optimal levels of purine byproducts and dynamics in clinical symptoms and adjustment, as well as in the integrity of sensory and motor processing. Taken together, alterations in purine catabolism may have clinical relevance in schizophrenia pathology

The Adoption and Implementation of Evidence-Based Practice (EBP) Among Allied Health Professions.

Background and aims: Evidence-based practice (EBP) is widely accepted within patient care as it ensures health care professionals remain informed of recent evidence and research relating to their clinical practice. However, the particular characteristics detrimental to the successful implementation of EBP within Allied Health Professionals' (AHP) clinical practice are unknown. The purpose of this study was to assess and characterise adoption of EBP within AHP's clinical practice. Methods: Questionnaires comprising the Evidence-Based Practice Questionnaire (EBPQ; Upton and Upton, 2006a) were administered to 154 (response rate=27.3%) newly qualified practitioners (NQPs) from NHSScotland. Data were analysed to determine attitudes, knowledge and skill of EBP; K-means cluster and chi-square analyses were conducted in order to differentiate profiles of NPQs within high-, medium- and low- categories on the EBPQ practice and knowledge/skills sub-sections. Findings: Moderate scores were recorded for NQP's implementation, knowledge, and attitudes toward EBP. Chi-square analysis performed on the high-, moderate- and low- practice and skills' profiles revealed no significant results for NQP's year qualified, age, or year of clinical practice. Conclusions: The findings illustrate that the majority of NQPs have a good understanding of the application and importance of EPB, and suggests the improvement in NQPs training with regards to EBP enables them to successfully transfer acquired knowledge within their clinical practice

Imaging haemodynamic changes related to seizures: comparison of EEG-based general linear model, independent component analysis of fMRI and intracranial EEG

Background: Simultaneous EEG-fMRI can reveal haemodynamic changes associated with epileptic activity which may contribute to understanding seizure onset and propagation. Methods: Nine of 83 patients with focal epilepsy undergoing pre-surgical evaluation had seizures during EEG-fMRI and analysed using three approaches, two based on the general linear model (GLM) and one using independent component analysis (ICA): 1. EEGs were divided into up to three phases: early ictal EEG change, clinical seizure onset and late ictal EEG change and convolved with a canonical haemodynamic response function (HRF) (canonical GLM analysis). 2. Seizures lasting three scans or longer were additionally modelled using a Fourier basis set across the entire event (Fourier GLM analysis). 3. Independent component analysis (ICA) was applied to the fMRI data to identify ictal BOLD patterns without EEG. The results were compared with intracranial EEG. Results: The canonical GLM analysis revealed significant BOLD signal changes associated with seizures on EEG in 7/9 patients, concordant with the seizure onset zone in 4/7. The Fourier GLM analysis revealed changes in BOLD signal corresponding with the results of the canonical analysis in two patients. ICA revealed components spatially concordant with the seizure onset zone in all patients (8/9 confirmed by intracranial EEG). Conclusion: Ictal EEG-fMRI visualises plausible seizure related haemodynamic changes. The GLM approach to analysing EEG-fMRI data reveals localised BOLD changes concordant with the ictal onset zone when scalp EEG reflects seizure onset. ICA provides additional information when scalp EEG does not accurately reflect seizures and may give insight into ictal haemodynamics

EEG correlated functional MRI and postoperative outcome in focal epilepsy

Background: The main challenge in assessing patients with epilepsy for resective surgery is localising seizure onset. Frequently, identification of the irritative and seizure onset zones requires invasive EEG. EEG correlated functional MRI (EEG-fMRI) is a novel imaging technique which may provide localising information with regard to these regions. In patients with focal epilepsy, interictal epileptiform discharge (IED) correlated blood oxygen dependent level (BOLD) signal changes were observed in approximately 50% of patients in whom IEDs are recorded. In 70%, these are concordant with expected seizure onset defined by non-invasive electroclinical information. Assessment of clinical validity requires post-surgical outcome studies which have, to date, been limited to case reports of correlation with intracranial EEG. The value of EEG-fMRI was assessed in patients with focal epilepsy who subsequently underwent epilepsy surgery, and IED correlated fMRI signal changes were related to the resection area and clinical outcome. Methods: Simultaneous EEG-fMRI was recorded in 76 patients undergoing presurgical evaluation and the locations of IED correlated preoperative BOLD signal change were compared with the resected area and postoperative outcome. Results: 21 patients had activations with epileptic activity on EEG-fMRI and 10 underwent surgical resection. Seven of 10 patients were seizure free following surgery and the area of maximal BOLD signal change was concordant with resection in six of seven patients. In the remaining three patients, with reduced seizure frequency post-surgically, areas of significant IED correlated BOLD signal change lay outside the resection. 42 of 55 patients who had no IED related activation underwent resection. Conclusion: These results show the potential value of EEG-fMRI in presurgical evaluation

The VLT-FLAMES Tarantula Survey XIX. B-type Supergiants - Atmospheric parameters and nitrogen abundances to investigate the role of binarity and the width of the main sequence

TLUSTY non-LTE model atmosphere calculations have been used to determine atmospheric parameters and nitrogen (N) abundances for 34 single and 18 binary B-type supergiants (BSGs). The effects of flux contribution from an unseen secondary were considered for the binary sample. We present the first systematic study of the incidence of binarity for a sample of BSGs across the theoretical terminal age main sequence (TAMS). To account for the distribution of effective temperatures of the BSGs it may be necessary to extend the TAMS to lower temperatures. This is consistent with the derived distribution of mass discrepancies, projected rotational velocities (vsini) and N abundances, provided that stars cooler than this temperature are post RSG objects. For the BSGs in the Tarantula and previous FLAMES surveys, most have small vsini. About 10% have larger vsini (>100 km/s) but surprisingly these show little or no N enhancement. All the cooler BSGs have low vsini of <70km/s and high N abundance estimates, implying that either bi-stability braking or evolution on a blue loop may be important. A lack of cool binaries, possibly reflects the small sample size. Single star evolutionary models, which include rotation, can account for the N enhancement in both the single and binary samples. The detailed distribution of N abundances in the single and binary samples may be different, possibly reflecting differences in their evolutionary history. The first comparative study of single and binary BSGs has revealed that the main sequence may be significantly wider than previously assumed, extending to Teff=20000K. Some marginal differences in single and binary atmospheric parameters and abundances have been identified, possibly implying non-standard evolution for some of the sample. This sample as a whole has implications for several aspects of our understanding of the evolution of BSGs. Full abstract in paperComment: 21 pages, 15 figures, 11 table

Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

The Current State of Performance Appraisal Research and Practice: Concerns, Directions, and Implications

On the surface, it is not readily apparent how some performance appraisal research issues inform performance appraisal practice. Because performance appraisal is an applied topic, it is useful to periodically consider the current state of performance research and its relation to performance appraisal practice. This review examines the performance appraisal literature published in both academic and practitioner outlets between 1985 and 1990, briefly discusses the current state of performance appraisal practice, highlights the juxtaposition of research and practice, and suggests directions for further research

Adaptation to Climate Change: Why is it Needed and How Can it be Implemented?

This is the 3rd study to be published in the CEPS Policy Brief series from ongoing research being carried out for the EU-funded ADAM project (ADaptation And Mitigation strategies: supporting European climate policy). Following an introduction to the aims and objectives of the ADAM project, section 2 sets out the rationales for public policy related to adaptation to the impacts of climatic change in the EU. Section 3 provides evidence from a number of stakeholders and sketches the perception of various actors towards the role of European adaptation policies and climate proofing of sectoral policies. Section 4 on the economics of adaptation argues that the economic impacts of climate change will mainly be reduced by private and autonomous response, while principal challenges are with adaptation needs that require collective action and public engagement, including public finance. Section 5 assesses monetary and socioeconomic risks from extreme weather events in Europe and points to the evidence of rising losses due to weather extremes whilst important knowledge gaps remain to project future risks. And the final section (6) deals with different concepts of uncertainties surrounding climate change and climate variability, and argues for adaptive measures to be sufficiently flexible to allow recalibration as uncertainties are reduced with time

The VLT-FLAMES Tarantula Survey X: Evidence for a bimodal distribution of rotational velocities for the single early B-type stars

Aims: Projected rotational velocities (\vsini) have been estimated for 334 targets in the VLT-FLAMES Tarantula survey that do not manifest significant radial velocity variations and are not supergiants. They have spectral types from approximately O9.5 to B3. The estimates have been analysed to infer the underlying rotational velocity distribution, which is critical for understanding the evolution of massive stars. Methods: Projected rotational velocities were deduced from the Fourier transforms of spectral lines, with upper limits also being obtained from profile fitting. For the narrower lined stars, metal and non-diffuse helium lines were adopted, and for the broader lined stars, both non-diffuse and diffuse helium lines; the estimates obtained using the different sets of lines are in good agreement. The uncertainty in the mean estimates is typically 4% for most targets. The iterative deconvolution procedure of Lucy has been used to deduce the probability density distribution of the rotational velocities. Results: Projected rotational velocities range up to approximately 450 \kms and show a bi-modal structure. This is also present in the inferred rotational velocity distribution with 25% of the sample having $0\leq$\ve$\leq$100\,\kms and the high velocity component having \ve$\sim 250$\,\kms. There is no evidence from the spatial and radial velocity distributions of the two components that they represent either field and cluster populations or different episodes of star formation. Be-type stars have also been identified. Conclusions: The bi-modal rotational velocity distribution in our sample resembles that found for late-B and early-A type stars. While magnetic braking appears to be a possible mechanism for producing the low-velocity component, we can not rule out alternative explanations.Comment: to be publisged in A&

Defining Meyer's loop-temporal lobe resections, visual field deficits and diffusion tensor tractography

Anterior temporal lobe resection is often complicated by superior quadrantic visual field deficits (VFDs). In some cases this can be severe enough to prohibit driving, even if a patient is free of seizures. These deficits are caused by damage to Meyer's loop of the optic radiation, which shows considerable heterogeneity in its anterior extent. This structure cannot be distinguished using clinical magnetic resonance imaging sequences. Diffusion tensor tractography is an advanced magnetic resonance imaging technique that enables the parcellation of white matter. Using seed voxels antero-lateral to the lateral geniculate nucleus, we applied this technique to 20 control subjects, and 21 postoperative patients. All patients had visual fields assessed with Goldmann perimetry at least three months after surgery. We measured the distance from the tip of Meyer's loop to the temporal pole and horn in all subjects. In addition, we measured the size of temporal lobe resection using postoperative T1-weighted images, and quantified VFDs. Nine patients suffered VFDs ranging from 22% to 87% of the contralateral superior quadrant. In patients, the range of distance from the tip of Meyer's loop to the temporal pole was 24–43 mm (mean 34 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was –15 to +9 mm (mean 0 mm). In controls the range of distance from the tip of Meyer's loop to the temporal pole was 24–47 mm (mean 35 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was –11 to +9 mm (mean 0 mm). Both quantitative and qualitative results were in accord with recent dissections of cadaveric brains, and analysis of postoperative VFDs and resection volumes. By applying a linear regression analysis we showed that both distance from the tip of Meyer's loop to the temporal pole and the size of resection were significant predictors of the postoperative VFDs. We conclude that there is considerable variation in the anterior extent of Meyer's loop. In view of this, diffusion tensor tractography of the optic radiation is a potentially useful method to assess an individual patient's risk of postoperative VFDs following anterior temporal lobe resection