Airborne Infection with Bacillus anthracis��from Mills to Mail

The lack of identified exposures in 2 of the 11 cases of bioterrorism-related inhalation anthrax in 2001 raised uncertainty about the infectious dose and transmission of Bacillus anthracis. We used the Wells-Riley mathematical model of airborne infection to estimate 1) the exposure concentrations in postal facilities where cases of inhalation anthrax occurred and 2) the risk for infection in various hypothetical scenarios of exposure to B. anthracis aerosolized from contaminated mail in residential settings. These models suggest that a small number of cases of inhalation anthrax can be expected when large numbers of persons are exposed to low concentrations of B. anthracis. The risk for inhalation anthrax is determined not only by bacillary virulence factors but also by infectious aerosol production and removal rates and by host factors.     

Assessing reproducibility for interval data in health-related quality of life questionnaires: Which coefficient should be used?

In contrast to other reliability estimates, test-retest reliability (or reproducibility) captures not only the measurement error of an assessment instrument, but also the stability of the construct measured. Consequently, one would expect any departure from identity (Y = X) of measurement pairs (X first, and Y second measurement) to be treated as 'error' by the respective reproducibility statistic, even if 'true' changes happened, e.g. worsening of a disease due to its natural course. The Pearson correlation, still often advocated for continuous measures in test-retest reliability studies, however captures the degree of linearity (Y = bX + a): perfect relationship can be computed, even if the measurement pairs differ not only by a additive constant 'a', but also because of a multiplication of the X-values with the slope 'b'. Therefore, intraclass correlation coefficients (ICCs) have been proposed as alternative statistics for reproducibility. However, only ICCs with absolute agreement definition of concordance capture the degree of identity. ICCs with a consistency definition of concordance measure the degree of additivity (Y = X + a). ICCs are calculated from repeated measures analyses of variance (ANOVAs), and a common population variance must be is assumed for the different measurements. Given this assumption, an ICC computed from a one-way ANOVA seems to be the best choice for this purpose. Otherwise, Lin's concordance correlation coefficient is recommended as identity measure.     

STATISTICAL INFERENCE FOR RELATIVE POTENCY IN BIVARIATE DOSE-RESPONSE ASSAYS WITH CORRELATED RESPONSES

ABSTRACT

The analysis of dose-response assays measuring two correlated responses is considered. Attention is given to statistical inference for the potency ratio. Results from a simulation study suggest that a post hoc adjustment for the correlation in parameter estimates obtained from univariate fits provides nearly as much power to detect differences in potency as a bivariate response model fit.     

Mechanical and physical properties of silorane and methacrylate-based composites

ObjectivesThis study measured the degree of conversion (DC), sorption, solubility and microhardness of methacrylate (Filtek Z250 and Filtek Z350XT) and silorane-based composites (Filtek P90).MethodsDC was measured using near infrared spectroscopy immediately and 24 h after the photoactivation. Sorption and solubility measurements were performed after 24 h, 4 weeks and 12 weeks of storage in water. Knoop microhardness was measured after 24 h and after thermal cycling. The data were statistically analyzed using ANOVA followed by Tukey's, Tamhane or paired t-tests (α = 0.05).ResultsThe DC for P90 (37.22 ± 1.46) was significantly lower than the Z250 (71.44 ± 1.66) and Z350 (71.76 ± 2.84). Water sorption was highest in the Z250 and lowest in the P90. All the tested composites exhibited similar values after 24 h of immersion, and no significant differences were observed. No significant differences were observed between the solubilities of the P90 composite (12 weeks) and the Z250 or Z350 composites (4 weeks). KHN values were less elevated for the P90 composite and similar for the Z250 and Z350 composites. An effect of thermal cycling on KHN values was observed for all the composites (p < 0.001).ConclusionsSilorane produced the lowest DC and KHN values and exhibited lower water sorption and solubility compared to methacrylate-based composites. These differences suggest that silorane composites exhibit better hydrolytic stability after 3 months of water immersion compared to conventional methacrylate-based composites.Clinical significanceSilorane had higher hydrolytic stability after 3 months of water immersion than the methacrylate-based resins, despite the lower values of DC and KHN recorded.     

Potential health risks to adults and children in the UK from exposure to dietary lead in gamebirds shot with lead ammunition

We estimate potential risks to human health in the UK from dietary exposure to lead from wild gamebirds killed by shooting. The main source of exposure to lead in Europe is now dietary. We used data on lead concentrations in UK gamebirds, from which gunshot had been removed following cooking to simulate human exposure to lead. We used UK food consumption and lead concentration data to evaluate the number of gamebird meals consumed weekly that would be expected, based upon published studies, to result in changes, over and above those resulting from exposure to lead in the base diet, in intelligence quotient (IQ), Systolic Blood Pressure and chronic kidney disease (CKD) considered in a recent opinion of the European Food Safety Authority (EFSA) to be significant at a population level and also in SAT test scores and in rates of spontaneous abortion. We found the consumption of <1 meal of game a week may be associated with a one point reduction in IQ in children and 1.2–6.5 gamebird meals per week may be associated with the other effects. These results should help to inform the development of appropriate responses to the risks from ingesting lead from ammunition in game in the UK and European Union (EU).     

Dosimetric comparison of IMRT rectal and anal canal plans generated using an anterior dose avoidance structure

To describe a dosimetric method using an anterior dose avoidance structure (ADAS) during the treatment planning process for intensity-modulated radiation therapy (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1 (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans were created: one employing an ADAS (ADAS plan) and the other replanned without an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the inguinal nodes and primary target providing a single organ at risk that is completely outside of the target volume. Each plan used the same beam parameters and was analyzed by comparing target coverage, overall plan dose conformity using a conformity number (CN) equation, bowel dose-volume histograms, and the number of segments, daily treatment duration, and global maximum dose. The ADAS and non-ADAS plans were equivalent in target coverage, mean global maximum dose, and sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 ± 0.03 (p < 0.001). The mean difference in the number of segments was 15.7 ± 12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter by 2.0 ± 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to be a powerful tool when planning rectal and anal canal IMRT cases with critical structures partially contained inside the target volume.     

Doses per vaccine vial container: An understated and underestimated driver of performance that needs more evidence

The widespread use of multidose vaccine containers in low and middle income countries’ immunization programs is assumed to have multiple benefits and efficiencies for health systems, yet the broader impacts on immunization coverage, costs, and safety are not well understood. To document what is known on this topic, how it has been studied, and confirm the gaps in evidence that allow us to assess the complex system interactions, the authors undertook a review of published literature that explored the relationship between doses per container and immunization systems. The relationships examined in this study are organized within a systems framework consisting of operational costs, timely coverage, safety, product costs/wastage, and policy/correct use, with the idea that a change in dose per container affects all of them, and the optimal solution will depend on what is prioritized and used to measure performance.Studies on this topic are limited and largely rely on modeling to assess the relationship between doses per container and other aspects of immunization systems. Very few studies attempt to look at how a change in doses per container affects vaccination coverage rates and other systems components simultaneously. This article summarizes the published knowledge on this topic to date and suggests areas of current and future research to ultimately improve decision making around vaccine doses per container and increase understanding of how this decision relates to other program goals.     

Pitfalls in rate and rhythm control: Severe concomitant orthostatic hypotension unmasked after conversion to sinus rhythm

Rate control is an acceptable strategy in management of patients with recurrent atrial fibrillation. Typically, it is more simple approach than rhythm control. Once optimal ventricular rate control is achieved patients with long-lasting atrial fibrillation commonly remain in good clinical status and do not require subsequent readmissions and change of prescribed drugs and their doses. We report a case of effective rate control strategy failure after relatively long period due to transformation of atrial fibrillation into atypical atrial flutter. Subsequent spontaneous conversion to sinus rhythm improved patient's hemodynamic but unmasked concomitant orthostatic hypotension that was severe and had significant impact on treatment of patient.Learning objectiveTransformation to atrial flutter may cause failure of rate control strategy even in previously stable patients with long time persistent atrial fibrillation. Spontaneous conversion to sinus rhythm can unmask orthostatic hypotension. Management of comorbid orthostatic hypotension might be challenging as it could be severe and have significant impact on patients’ condition.     

Evaluation of exposure–response relationships for health effects of microbial bioaerosols – A systematic review

Studies suggest adverse health effects following exposure to bioaerosols in the environment and in particular at workplaces. However, there is still a lack of health-related exposure limits based on toxicological or epidemiological studies from environmental health or from the working environment. The aim of this study was to derive health-based exposure limits for bioaerosols that can protect the general population as group “at risk” via environmental exposure using analysis of peer-reviewed studies related to occupational medicine, indoor air and environmental health. The derivation of exposure limits should be conducted by the members of a bioaerosol expert panel according to established toxicological criteria. A systematic review was performed in Medline (PubMed) including studies containing both data on exposure measurements and observed health outcomes. In addition, literature recommended by the experts was considered. A comprehensive search strategy was generated and resulted in a total of n = 1569 studies in combination with the literature recommendations. Subsequently, abstracts were screened using defined exclusion criteria yielding a final number of n = 44 studies. A standardized extraction sheet was used to combine data on health effects and exposure to different bioaerosols. After full-text screening and extraction according to the defined exclusion criteria n = 20 studies were selected all related to occupational exposures comprising the working areas wood processing, farming, waste processing and others. These studies were analyzed in collaboration with the bioaerosol expert network in terms of suitability for derivation of health-related exposure limits. The bioaerosol expert network concluded that none of the analyzed studies provided suitable dose–response relationships for derivation of exposure limits. The main reasons were: (1) lack of studies with valid dose–response data; (2) diversity of employed measuring methods for microorganisms and bioaerosol-emitting facilities; (3) heterogeneity of health effects; (4) insufficient exposure assessment. However, several indicator parameters and exposure concentrations could be identified for different bioaerosol-emitting facilities. Nevertheless, health-related exposure limits are urgently needed especially in approval procedures of facilities like composting plants or livestock farms emitting bioaerosols in the neighbourhood of residents. In the regulatory toxicology framework, it is common to use animal experimental studies for derivation of general exposure limits if appropriate environmental epidemiological studies on harmful substances are lacking. This might be another possibility to obtain health-related exposure limits for specific bioaerosol parameters. Furthermore, we recommend to use suitable measurable outcome parameters related to bioaerosols; to measure bioaerosols according to a protocol representative for exposure pattern and duration at the particular work place; to develop standardized detection methods for indicator parameters; to combine different detection methods to compensate for the limitations of each method; to apply new analysis methods to identify the real risk potential.