Seroprotection against tetanus in patients attending an emergency department in Belgium and evaluation of a bedside immunotest.

BACKGROUND: In most emergency departments, tetanus prophylaxis currently relies on vaccination history. Bedside evaluation of tetanus immunity may improve this process. OBJECTIVES: (i) To determine the seroprevalence of tetanus immunity; (ii) to evaluate the accuracy of vaccination history in assessing tetanus immunity; (iii) to identify factors predictive of seroprotection and incorrect history. METHOD: In a prospective observational study, tetanus immunity was assessed in 784 adults using Tétanos Quick Stick (TQS). A questionnaire was completed to obtain vaccination and general histories. Immunity assessed by TQS and by vaccination history were compared with anti-tetanus antibody levels measured by the enzyme-linked immunosorbent assay (seroprotection threshold >0.15 IU/ml). RESULTS: Overall, 64.2% of patients were protected according to TQS results. Four independent predictors of seroprotection were identified: young age, birthplace in Belgium, male sex and occupational medicine consultation. TQS performance was good: kappa=0.71, sensitivity 85.3%, specificity 87.2%, positive predictive value 92.1% and negative predictive value 77.2%. Seven hundred and sixty-two participants responded to the vaccination history: 23.4% said they were protected, 22.1% that they were not and 54.5% did not know. History performance was poor: kappa=0.27, sensitivity 60.3%, specificity 73.3%, positive predictive value 81.8% and negative predictive value 45.8%. Compared with history, TQS offered a significantly better sensitivity, negative and positive predictive values, but specificity was similar. No predictor of an incorrect history was identified. CONCLUSION: Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.

Dynamic model for metal cleanness evaluation by melting in a cold crucible

Melting of metallic samples in a cold crucible causes inclusions to concentrate on the surface owing to the action of the electromagnetic force in the skin layer. This process is dynamic, involving the melting stage, then quasi-stationary particle separation, and finally the solidification in the cold crucible. The proposed modeling technique is based on the pseudospectral solution method for coupled turbulent fluid flow, thermal and electromagnetic fields within the time varying fluid volume contained by the free surface, and partially the solid crucible wall. The model uses two methods for particle tracking: (1) a direct Lagrangian particle path computation and (2) a drifting concentration model. Lagrangian tracking is implemented for arbitrary unsteady flow. A specific numerical time integration scheme is implemented using implicit advancement that permits relatively large time-steps in the Lagrangian model. The drifting concentration model is based on a local equilibrium drift velocity assumption. Both methods are compared and demonstrated to give qualitatively similar results for stationary flow situations. The particular results presented are obtained for iron alloys. Small size particles of the order of 1 μm are shown to be less prone to separation by electromagnetic field action. In contrast, larger particles, 10 to 100 μm, are easily “trapped” by the electromagnetic field and stay on the sample surface at predetermined locations depending on their size and properties. The model allows optimization for melting power, geometry, and solidification rate.

Toward autonomous measurements of photosynthetic electron transport rates: An evaluation of active fluorescence-based measurements of photochemistry

This study presents a methods evaluation and intercalibration of active fluorescence-based measurements of the quantum yield ( inline image) and absorption coefficient ( inline image) of photosystem II (PSII) photochemistry. Measurements of inline image, inline image, and irradiance (E) can be scaled to derive photosynthetic electron transport rates ( inline image), the process that fuels phytoplankton carbon fixation and growth. Bio-optical estimates of inline image and inline image were evaluated using 10 phytoplankton cultures across different pigment groups with varying bio-optical absorption characteristics on six different fast-repetition rate fluorometers that span two different manufacturers and four different models. Culture measurements of inline image and the effective absorption cross section of PSII photochemistry ( inline image, a constituent of inline image) showed a high degree of correspondence across instruments, although some instrument-specific biases are identified. A range of approaches have been used in the literature to estimate inline image and are evaluated here. With the exception of ex situ inline image estimates from paired inline image and PSII reaction center concentration ( inline image) measurements, the accuracy and precision of in situ inline image methodologies are largely determined by the variance of method-specific coefficients. The accuracy and precision of these coefficients are evaluated, compared to literature data, and discussed within a framework of autonomous inline image measurements. This study supports the application of an instrument-specific calibration coefficient ( inline image) that scales minimum fluorescence in the dark ( inline image) to inline image as both the most accurate in situ measurement of inline image, and the methodology best suited for highly resolved autonomous inline image measurements.

An Evaluation of the Impact of the Prospective Payment System on Antidepressant Use in Nursing Home Residents

Objectives: To determine the impact of the prospective payment system (PPS) for skilled nursing facilities on the pharmacologic treatment of depression.

Methods: We used a quasi-experimental study comparing the pharmacological treatment rates for depression in the pre-PPS period (1997) to the post-PPS period (2000) in 8149 residents with documented depression living in over 500 nursing facilities in Ohio. Logistic regression models adjusting for clustering effects of residents residing in homes using generalized estimating equations provided estimates of the PPS effect on use of any antidepressant and the use of selective serotonin reuptake inhibitors (SSRIs). We evaluated the extent to which the PPS effect was modified by organizational characteristics, including structural characteristics, resource characteristics, and staff resources available in the homes.

Results: Overall, there was no difference in the likelihood of any antidepressant [odds ratio (OR), 1.05; 95% confidence interval (CI), 0.93 to 1.18, resident-adjusted model] or an SSRI being used (OR, 0.98; 95% CI, 0.86 to 1.12, resident-adjusted model) after the introduction of PPS compared with 1997 when this reimbursement system was not in place (referent group). These trends did not appear to be modified substantially by organizational characteristics.

Conclusion: Although PPS did not appear to have influenced the treatment of depression in nursing homes, systems that provide checks and balances in relation to PPS are warranted.

Evaluation of a Water-soluble Bioadhesive Patch for Photodynamic Therapy of Vulval Lesions

An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 N cm-2. Patient evaluation demonstrated comfort and firm attachment for up to 4 h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.

Predictors of therapy resistant asthma: outcome of a systematic evaluation protocol

Background: It has been suggested that asthmatic subjects with persisting symptoms despite adequate maintenance therapy should be systematically evaluated to identify factors contributing to poor control. The aims of this study were to examine the prevalence of these factors in a cohort of sequentially referred poorly controlled asthmatics, and to determine if any factor or combination of factors predicted true therapy resistant asthma (TRA).

Methods: Patients were evaluated using a systematic evaluation protocol including induced sputum analysis, psychiatric assessment, ear, nose and throat examination, pulmonary function testing, high resolution CT scan of the thorax, and 24 hour dual probe ambulatory oesophageal pH monitoring; any identified provoking factor was treated. Asthma was managed according to BTS guidelines.

Results: Of 73 subjects who completed the assessment, 39 responded to intervention and 34 had TRA. Subjects with TRA had a greater period of instability, a higher dose of inhaled steroids at referral, more rescue steroid use, and a lower best percentage forced expiratory volume in 1 second (FEV1%). Oesophageal reflux, upper airway disease, and psychiatric morbidity were common (57%, 95%, 49%, respectively) but were not more prevalent in either group. Using multivariate logistic regression analysis, inhaled steroid dose >2000 µg BDP, previous assessment by a respiratory specialist, and initial FEV1% of <70% at referral predicted a final diagnosis of TRA.

Conclusions: In poorly controlled asthmatics there is a high prevalence of co-morbidity, identified by detailed systematic assessment, but no difference in prevalence between those who respond to intervention and those with TRA. Targeted treatment of identified co-morbidities has minimal impact on asthma related quality of life in those with therapy resistant disease.

Sex Education in Northern Ireland Schools: a Critical Evaluation.

To date there has been little research on young people and sexuality in Northern Ireland. This paper draws on the first major study in this area to analyse the delivery of formal sex education in schools. Both quantitative and qualitative methods were used to access young people's opinions about the quality of the sex education they had received at school. Overall, they reported high levels of dissatisfaction, with notable variations in relation to both gender and religious affiliation. In one sense their opinions mesh well with those of young people in other parts of these islands. At the same time the specificity of sexuality in Ireland plays a key role in producing the moral system that underlies much of formal sex education in schools. Underpinned by a particularly traditional and conservative strain of Christian morality, sex education in Northern Ireland schools is marked by conservatism and silence and by the avoidance of opportunities for informed choice in relation to sexuality on the part of young people.

Evaluation of predicted network modules in yeast metabolism using NMR-based metabolite profiling

Genome-scale metabolic models promise important insights into cell function. However, the definition of pathways and functional network modules within these models, and in the biochemical literature in general, is often based on intuitive reasoning. Although mathematical methods have been proposed to identify modules, which are defined as groups of reactions with correlated fluxes, there is a need for experimental verification. We show here that multivariate statistical analysis of the NMR-derived intra- and extracellular metabolite profiles of single-gene deletion mutants in specific metabolic pathways in the yeast Saccharomyces cerevisiae identified outliers whose profiles were markedly different from those of the other mutants in their respective pathways. Application of flux coupling analysis to a metabolic model of this yeast showed that the deleted gene in an outlying mutant encoded an enzyme that was not part of the same functional network module as the other enzymes in the pathway. We suggest that metabolomic methods such as this, which do not require any knowledge of how a gene deletion might perturb the metabolic network, provide an empirical method for validating and ultimately refining the predicted network structure.

An evaluation of cyclooxygenase-2 as a prognostic biomarker in mid-gut carcinoid tumours

Background/Aims:Mid-gut carcinoids (MGC) are the most common of the gastrointestinal carcinoid tumours. There is a lack of reliable prognostic indicators for MGC. Cox-2 and Bcl-2 were evaluated as prognostic biomarkers in a cohort of well-characterised non-appendiceal MGC. Methods: Tissue from the primary MGC tumours of 37 patients was subjected to immunohistochemical detection of Cox-2 and Bcl-2. In 9 cases tissue from secondary lesions was also examined. The study assessed whether tumour-associated Cox-2 and Bcl-2 expression were related to patient survival. Results: Cox-2 expression was demonstrated in 30/36 primary tumours. When all tumours were analysed Cox-regression analysis indicated a trend towards worsening survival with increasing Cox-2 histoscore (intensity x proportion; hazard ratio 1.53, 95%CI 0.93, 2.52; p=0.09). Analysis of Cox-2 positive tumours revealed a highly significant association between increasing histoscore and decreased survival (hazard ratio 3.03, 95%CI 1.33, 6.91, p=0.008). Tumour-associated Bcl-2 expression had no effect on patient survival (hazard ratio 1.12, 95% CI 0.42, 2.99 p=0.82). There was no significant association between Cox-2 and Bcl-2 expression (ï?£2 p=0.16), or Cox-2 histoscore and Bcl-2 expression (MWU p=0.59). Analysis of the Cox-2 histoscores of primary tumours and their corresponding secondary lesions, revealed a statistically significant trend towards increasing histoscore in the latter (Wilcoxon p=0.04). Conclusions: This study has provided evidence that Cox-2 expression in primary MGC may be associated with a more negative prognostic outlook.

Comparative evaluation of 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)2H-tetrazolium, monosodium salt (WST-8) rapid colorimetric assays for antimicrobial susceptibility testing of staphylococci and ESBL-producing clinical isolates

A new generation of water soluble tetrazolium salts have recently become available and in this study we compared a colorimetric assay developed using one of these salts, 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8), with a previously developed 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide(XTT) colorimetric assay to determine which agent is most suitable for use as a colorimetric indicator in susceptibility testing. The MICs of 6 antibiotics were determined for 33 staphylococci using both colorimetric assays and compared with those obtained using the British Society for Antimicrobial Chemotherapy reference broth microdilution method. Absolute categorical agreement between the reference and test methods ranged from 79% (cefuroxime) to 100% (vancomycin) for both assays. No minor or major errors occurred using either assay with very major errors ranging from zero (vancomycin) to seven (cefuroxime). Analysis of the distribution of differences in the 1092 dilution MIC results revealed overall agreement, within the accuracy limits of the standard test ( 1 1092 dilution), using the XTT and WST-8 assays of 98% and 88%, respectively. Further studies on 31 ESBL-producing isolates were performed using the XTT method with absolute categorical agreement ranging from 87% (nitrofurantoin) to 100% (ofloxacin and meropenem). No errors were noted for either ofloxacin or meropenem with overall agreement of 91%. The data suggests that XTT is more reliable and accurate than WST-8 for use in a rapid antimicrobial susceptibility test. (c) 2007 Elsevier B.V. All rights reserved.

Substrate evaluation for a microbeam endstation using unstained cell imaging.

A cellular imaging system, optimized for unstained cells seeded onto a thin substrate, is under development. This system will be a component of the endstation for the microbeam cell-irradiation facility at the University of Surrey. Previous irradiation experiments at the Gray Cancer Institute (GCI) have used Mylar film to support the cells [Folkard, M., Prise, K., Schettino, G., Shao, C., Gilchrist, S., Vojnovic, B., 2005. New insights into the cellular response to radiation using microbeams. Nucl. Instrum. Methods B 231, 189-194]. Although suitable for fluorescence microscopy, the Mylar often creates excessive optical noise when used with non-fluorescent microscopy. A variety of substrates are being investigated to provide appropriate optical clarity, cell adhesion, and radiation attenuation. This paper reports on our investigations to date.

Evaluation of N (epsilon)-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy.

AIMS/HYPOTHESIS: Recent studies suggest that oxidative stress should be monitored alongside HbA(1c) to identify subgroups of diabetic patients at high risk of initiation or progression of retinopathy. The acrolein-derived advanced lipoxidation end-product (ALE), [Formula: see text]-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine), is a useful biomarker that reflects the cumulative burden of oxidative stress over long periods of time. The purpose of the present study was to investigate whether serum and haemoglobin levels of FDP-lysine are associated with the severity of diabetic retinopathy in type 1 and type 2 diabetic patients.

METHODS: Serum and haemoglobin levels of FDP-lysine were measured by competitive ELISA in 59 type 1 and 76 type 2 diabetic patients with no retinopathy, non-proliferative retinopathy or proliferative retinopathy (mean age [+/-SEM] 54.3 +/- 1.3 years), and in 47 non-diabetic control individuals (mean age 51.9 +/- 2.1 years).

RESULTS: Serum and haemoglobin levels of FDP-lysine were significantly increased in diabetic patients compared with control individuals (p = 0.04 and p = 0.002, respectively). However, no significant association was found between levels of serum FDP-lysine and the severity of diabetic retinopathy (p = 0.97). In contrast, increased haemoglobin FDP-lysine levels were observed in patients with proliferative retinopathy compared with patients without retinopathy and with non-proliferative retinopathy (p = 0.04). The relationship of FDP-lysine with proliferative retinopathy was unaltered after adjustment for HbA(1c), or other clinical parameters.

CONCLUSIONS/INTERPRETATION: Our data suggest that haemoglobin FDP-lysine may provide a useful risk marker for the development of proliferative diabetic retinopathy independently of HbA(1c), and that elevated intracellular ALE formation may be involved in the pathogenesis of this sight-threatening complication of diabetes.

Development and evaluation of a vaginal ring device for sustained delivery of HIV microbicides to non-human primate

Background There is considerable interest in developing coitally indepen- dent, sustained release formulations for long-term administration of HIV microbicides. Vaginal ring devices are at the forefront of this formulation strategy. Methods Non-medicated silicone elastomer vaginal rings were prepared having a range of appropriate dimensions for testing vaginal ?t in pig- tailed and Chinese rhesus macaques. Cervicovaginal proin?ammatory markers were evaluated. Compression testing was performed to compare the relative ?exibility of various macaque and commercial human rings. Results All rings remained in place during the study period and no tissue irritation or signi?cant induction of cervicovaginal proin?ammatory mark- ers or signs of physical discomfort were observed during the 8-week study period. Conclusions Qualitative evaluation suggests that the 25 · 5-mm ring pro- vided optimal ?t in both macaque species. Based on the results presented here, low-consistency silicone elastomers do not cause irritation in maca-

Evaluation of a Microfluidic Device for the Electrochemical Determination of Halide Content in Ionic Liquids

A microfluidic device designed for electrochemical studies on a microliter scale has been utilized for the examination of impurity levels in ionic liquids (ILs). Halide impurities are common following IL synthesis, and this study demonstrates the ability to quantify low concentrations of halide in a range of ILs to levels of similar to 5 ppm, even in ILs not currently measurable using other methods such as ion chromatography. To validate the mixer device, the electrochemistry of ferrocene was also examined and compared with spectroscopic and bulk electrochemistry measurements. An automated