The majority of particles that adhere to hands are <63 μm in diameter yet risk assessments for soil remediation are typically based on soil samples sieved to <250 μm. The objective of our study was to determine if there is a significant difference in metal concentration by particle size in both house dust and soil. We obtained indoor dust and yard soil samples from 10 houses in Tucson, Arizona. All samples were sieved to <63 μm and 63 to <150 μm and analyzed for 30 elements via ICP-MS following nitric acid digestion. We conducted t-tests of the log-transformed data to assess for significant differences that were adjusted with a Bonferroni correction to account for multiple comparisons. In house dust, significant differences in concentration were observed for Be, Al, and Mo between particles sizes, with a higher concentration observed in the smaller particle sizes. Significant differences were also determined for Mg, Ca, Cr, Co, Cu, Ge, Zr, Ag, Ba, and Pb concentration in yard soil samples, with the higher concentration observed in the smaller particles size for each element. The results of this exploratory study indicate that current risk assessment practices for soil remediation may under estimate non-dietary ingestion exposure. This is of particular concern for young children who are more vulnerable to this exposure route due to their high hand mouthing frequencies. Additional studies with a greater number of samples and wider geographic distribution with different climates and soil types should be completed to determine the most relevant sampling practices for risk assessment.

We present measurements of J/ψ yields in d+Au collisions at sqrt[s(NN)]=200  GeV recorded by the PHENIX experiment and compare them with yields in p+p collisions at the same energy per nucleon-nucleon collision. The measurements cover a large kinematic range in J/ψ rapidity (-2.2<y<2.4) with high statistical precision and are compared with two theoretical models: one with nuclear shadowing combined with final state breakup and one with coherent gluon saturation effects. In order to remove model dependent systematic uncertainties we also compare the data to a simple geometric model. The forward rapidity data are inconsistent with nuclear modifications that are linear or exponential in the density weighted longitudinal thickness, such as those from the final state breakup of the bound state.

UNLABELLED WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • While the new H1N1 vaccines underwent the usual rigorous safety and efficacy testing, concerns remained that there may be unexpected side effects of the vaccines. • The strategy for H1N1 vaccine pharmacovigilance in the UK consisted of two patient studies by the two vaccine manufacturers, 14 small scale studies supported by the National Institute of Health Research, monitoring by specialist neurologists and the MHRA. • There were calls to investigate the feasibility of a large-scale prospective active surveillance system for 'near real-time' vaccine safety monitoring that would be complementary to the other aforementioned initiatives. WHAT THIS STUDY ADDS • This pilot study demonstrated that collecting 'near real-time' reporting of event data from patients who experienced side effects as well as those who reported no problems after swine flu vaccination is feasible. • The use of information technologies improves patient involvement in research as well as dramatically limiting the cost of the study. • The online methodology facilitates rapid surveillance in response to urgent safety issues. AIMS During the global H1N1 influenza A (swine flu) pandemic 2009-2010, swine flu vaccines were expeditiously licensed and a mass vaccination programme for high risk groups, including pregnant women, was introduced in the UK. This pilot active safety surveillance study was performed to establish the feasibility of rapidly monitoring the new swine flu vaccines in large patient numbers receiving or offered the vaccination under normal conditions of use within a short time frame. METHODS A cohort design with safety data capture through modern technologies was carried out in Scotland, UK during the winter swine flu vaccination programme 2009-2010 in individuals receiving or offered the swine flu vaccination. The main outcome measures were self-reported serious adverse events (SAEs) and pregnancy outcomes. RESULTS The cohort comprised 4066 people; 3754 vaccinated and 312 offered the vaccination but not vaccinated. There were 939 self-reported events (838 different events), 53 judged to fit SAE criteria by the investigators, with nine judged as possibly, probably or definitely vaccine related. None of the seven deaths (six in vaccinees) were judged as vaccine related. One hundred and twenty-eight women reported 130 pregnancies during the study with 117 pregnant at study start. There were reports of four miscarriages in three women and six possible congenital abnormalities in live births. CONCLUSIONS Overall, no significant safety issues were identified. The methodology and use of modern technologies to collect safety data from large numbers of patients was successful and could be used again in similar safety studies.

Prescription-Event Monitoring (PEM) is a well established postmarketing surveillance technique designed to monitor the overall safety of newly marketed medicines as used in real-life clinical practice, usually in cohorts of at least 10 000 patients. At the Drug Safety Research Unit in the UK we are now moving towards a more targeted safety surveillance known as Modified PEM (M-PEM). These studies combine the advantages of conventional PEM studies (in monitoring general safety and identification of unexpected risks of a medicine) with that of a more targeted safety study that addresses specific questions (to better understand known or partially known risks with a medicine). Through the use of enhanced data collection questionnaires, M-PEM expands the range of applications of conventional PEM, which include more detailed characterization of real-life drug use, adherence to prescribing recommendations and targeted analysis of events requiring special monitoring by regulatory authorities. A particularly useful application is the evaluation of the safety of a medicine in special populations or subgroups (e.g. patients switching from another therapy or patients with a particular risk factor) or following important changes in the product's lifecycle (e.g. a licensing or formulation change). M-PEM studies therefore have an important contribution to make to pharmacovigilance and the risk management of medicines by providing valuable information on the use of new medications under real-life situations.

BACKGROUND Levocetirizine was launched onto the UK market in September 2001. It is indicated for symptomatic treatment of allergic rhinitis (AR), including persistent AR and chronic idiopathic urticaria. OBJECTIVE The aim of the study was to monitor the safety of levocetirizine prescribed in the primary care setting in England, in the immediate postmarketing period. METHODS Exposure data were derived from dispensed prescriptions written by primary care physicians (general practitioners [GPs]) for levocetirizine (November 2001-November 2002): patient demographic, indication, pattern of use and outcome (event) data from enhanced prescription-event monitoring (PEM) questionnaires (with additional questions to gather further relevant information) returned by GPs. Incidence density observation rates (IDobs)[number of first reports/1000 patient-months] between months 1 and 2 (IDobs(m1/m2)) were compared for the whole cohort and by groups defined by indication and pattern of use. RESULTS The cohort comprised 12 367 patients (median age 37 years [interquartile range 22-55]; 58% female). The most frequent indication was AR (67%; n = 8275). After 2 months, 35.7%(n = 2414) of patients were still taking levocetirizine.'Condition improved' was the most common event and reason for stopping treatment. Headache/migraine was uncommon but associated with starting treatment (IDobs(m1/m2) 2.4 [95% CI 1.1, 6.0]), as was drowsiness/sedation (IDobs(m1/m2) 11.5 [95% CI 4.2, 43.9]). Cardiovascular events occurred rarely or very rarely, as did most central and peripheral nervous system events. No serious adverse drug reactions (ADRs) were reported. Events related to effectiveness were more frequent in month 1 than month 2 for all patient subgroups. CONCLUSIONS This postmarketing surveillance study shows that levocetirizine is well tolerated when used in general practice in England. No previously unrecognized ADRs were detected. This study highlights how modifications to PEM, such as additional questions, are contributing to the evaluation of drug utilization factors in relation to risks.

Prescription-Event Monitoring (PEM) is a well established postmarketing surveillance technique designed to monitor the overall safety of newly marketed medicines as used in real-life clinical practice, usually in cohorts of at least 10 000 patients.At the Drug Safety Research Unit in the UK we are now moving towards a more targeted safety surveillance known as Modified PEM (M-PEM). These studies combine the advantages of conventional PEM studies (in monitoring general safety and identification of unexpected risks of a medicine) with that of a more targeted safety study that addresses specific questions (to better understand known or partially known risks with a medicine). Through the use of enhanced data collection questionnaires, M-PEM expands the range of applications of conventional PEM, which include more detailed characterization of real-life drug use, adherence to prescribing recommendations and targeted analysis of events requiring special monitoring by regulatory authorities. A particularly useful application is the evaluation of the safety of a medicine in special populations or subgroups (e.g. patients switching from another therapy or patients with a particular risk factor) or following important changes in the product's lifecycle (e.g. a licensing or formulation change). M-PEM studies therefore have an important contribution to make to pharmacovigilance and the risk management of medicines by providing valuable information on the use of new medications under real-life situations.

Purpose: This paper aimed to practice evidence-based dentistry by critically appraising relevant evidence to address a common question in prosthodontics. It sought to answer whether the survival and complication rates of all-ceramic fixed dental prostheses (FDPs) were comparable or superior to those of metal-ceramic FDPs, and to use this knowledge to guide clinical decisions. Materials and Methods: A 6S search was conducted. No decision support systems or summaries were available. The journal Evidence-Based Dentistry (zero synopses), Trip database (three synopses, discarded), Cochrane database (three systematic reviews, discarded), MEDLINE OVID (six systematic reviews, one accepted), and Embase (zero systematic reviews) were searched. The selected systematic review assessed the survival and complication rates of all-ceramic and metal-ceramic FDPs. One additional prospective cohort study was considered relevant. Results: The systematic review addressed a well-focused clinical question, but its internal validity was compromised. The search was not systematic; inclusion methodology and impact of study characteristics on results were unclear. The external applicability was limited by compromised internal validity, broad outcome definitions, inaccurate results, and incomplete examination of stated aims. With care, however, the results could be applied to clinical practice. Estimated event rates and 5-year outcomes with a 95% confidence interval were calculated, with the survival rate of metal-ceramic FDPs significantly higher than that of all-ceramic FDPs. All-ceramic FDPs experienced a high incidence of technical failure. The prospective cohort addressed a well-focused clinical question with good internal validity. It compared outcomes of metal-ceramic FDPs provided before and after the introduction of implant therapy. Patient cohorts were clearly defined, similar at baseline, and treated equally. Ten-year Kaplan-Meier cumulative survival with standard errors was reported. Metal-ceramic FDP survival rates were high and significantly improved since the introduction of implants and the decreased use of structurally compromised abutments. Conclusion: The results of the systematic review and prospective cohort were complementary: Metal-ceramic FDPs had high survival, with a significantly greater 5-year survival rate than all-ceramic FDPs. Differences in complications were unknown, but evidence indicated that the complication incidence of metal-ceramic FDPs was lower than that of all-ceramic FDPs. This evidence was directly applicable to the clinical scenario and will help guide clinical decision making. Int J Prosthodont 2011;24:417-427.

INTRODUCTION Ibandronic acid 150 mg/month (Bonviva) is a bisphosphonate that was licensed in the UK in 2005 for the treatment of postmenopausal osteoporosis in women. Prescription-event monitoring (PEM) is a non-interventional observational cohort technique conducted by the Drug Safety Research Unit to monitor the safety of newly marketed drugs prescribed in general practice in England. OBJECTIVE To describe the utilization characteristics of the patients prescribed ibandronic acid based on an analysis of a completed PEM cohort and to assess, where possible, if the product is being used outside terms of license of marketing approval. METHODS An observational cohort PEM study was conducted. Exposure data were collected from dispensed prescriptions issued by general practitioners (GPs) between November 2005 and November 2007. Outcome data (event, patient demographic and selected clinical characteristics) were collected by sending questionnaires (green forms) to GPs at least six months after the drug was first prescribed for an individual patient. Summary descriptive statistics were calculated. For this study, menopause was defined by female age at 50+ years. RESULTS The cohort consisted of 11,034 patients, of which 9%(n = 991 patients) were reported to be men. Where age was specified, 4.8%(529/11,017) were aged <50 years, of which 0.4%(2/529) were <20 years. A total of 398 deaths occurred (3.6% cohort). Where specified, primary indications other than postmenopausal osteoporosis were reported for 11.7%(1218/10,446) patients including 'prophylaxis'(n = 715),'osteopenia'(n = 231) and 'fracture spontaneous'(n = 41). The most frequently reported clinical reasons for stopping treatment were 'intolerance'(n = 176) and 'dyspepsia'(n = 158). There was one pregnancy, reported as the reason for stopping treatment. Where dose was specified, 99.9% of patients (8625/8637) were prescribed the approved dose of 150 mg per month. CONCLUSION This study has highlighted that some clinicians are prescribing this product outside the recommended terms of the licence. Use in premenopausal women and men was reported. This study assumed natural menopause occurred when aged 50+ years, though this does not apply for surgically menopausal women. Prescribing for indications other than osteoporosis was common, but unusual dose regimens were uncommon. Drug utilization studies are important in describing populations that may not have been adequately studied in terms of risk in premarketing development programmes and are important in the postmarketing risk management of medicines.

Levoglucosan is a major product of biomass pyrolysis. While this pyrolyzed biomass, also known as bio-oil, contains sugars that are an attractive fermentation substrate, commonly-used biocatalysts, such as Escherichia coli, lack the ability to metabolize this anhydrosugar. It has previously been shown that recombinant expression of the levoglucosan kinase enzyme enables use of levoglucosan as carbon and energy source. Here, ethanologenic E. coli KO11 was engineered for levoglucosan utilization by recombinant expression of levoglucosan kinase from Lipomyces starkeyi. Our engineering strategy uses a codon-optimized gene that has been chromosomally integrated within the pyruvate to ethanol (PET) operon and does not require additional antibiotics or inducers. Not only does this engineered strain use levoglucosan as sole carbon source, but it also ferments levoglucosan to ethanol. This work demonstrates that existing biocatalysts can be easily modified for levoglucosan utilization.

Purpose: The aim of this study was to develop and verify the reliability and validity of a questionnaire to assess patient satisfaction with fixed dental prostheses (FDPs). Materials and Methods: A questionnaire was developed, pilot-tested, and modified. It assessed esthetics, masticatory function, phonetics, cleansibility, and cost satisfaction using a visual analog scale and whether patients would elect to undergo the same treatment again (yes/no). It was sent to patients with a known evidence-based outcome (survival) who received FDPs from 1984 to 2005 (n = 986) in one private prosthodontic practice. Reliability and validity were analyzed using the Student t, Mann-Whitney U, Kruskal Wallis, Cronbach alpha, Spearman-Brown, Correlation matrix, Bartlett sphericity, Kaiser-Meyer-Olkin (KMO), and factor analysis tests. Significance was set at P =.05. Results: Five hundred patients responded (50.7%). A Cronbach alpha value of 0.8 and split-sample Spearman-Brown value of 0.7 indicated good reliability. Step-wise removal of items did not improve internal consistency. Discriminant construct validity assessment showed no item redundancy. Satisfaction of patients who had experienced prosthesis failure (n = 52) was significantly less than their counterparts (73% ± 3% vs 83% ± 0.6%, P =.004), ascertaining convergent construct validity. Factor analysis (Bartlett sphericity, P <.001; KMO = 0.84) identified two components (Eigenvalues ⋝ 1.0) that explained 93.18%(varimax rotation) of variations. Component 1 included satisfaction with function (esthetics, mastication, phonetics, and cleansibility); component 2 included satisfaction with costs and whether patients would undergo the same treatment again. Conclusions: The Patient Satisfaction Questionnaire developed proved reliable and valid for assessing patient-evaluated outcomes of FDPs. Use of this questionnaire in further research is justified. Int J Prosthodont 2011;24:332-341.