The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies.

BACKGROUND: Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. METHODS: To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. RESULTS: GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. CONCLUSION: The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.

Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers.

BACKGROUND: Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival. METHODS: Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays. RESULTS: High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas. CONCLUSIONS: GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.

Discovery of novel glioma serum biomarkers by proximity extension assay.

BACKGROUND: Gliomas are among the most malignant tumors, with a very poor prognosis. Early diagnosis is highly desirable since it can help implement more effective treatments for smaller tumors, which have not yet extensively metastasized. Improving early diagnosis may facilitate access of patients to clinical trials and prepare them for the future availability of new disease-modifying treatments. METHODS: We analyzed retrospective samples collected at diagnosis (before therapy initiation), with PEA (Olink Proteomics), quantifying about 3000 proteins. We utilized 30 plasmas from gliomas (20 glioblastomas, 5 anaplastic astrocytomas, 5 anaplastic oligodendrogliomas) and 20 meningiomas (as controls). We then analyzed the data to identify proteins which either alone, or in combination, could discriminate gliomas from meningiomas, or correlate with clinical and molecular alterations. RESULTS: We identified 8 plasma proteins which were increased in gliomas vs. meningiomas (GFAP, NEFL, EDDM3B, PROK1, MMP3, CTRL, GP2, SPINT3) and 4 proteins which were decreased in gliomas vs. meningiomas (FABP4, ALDH3A1, IL-12B and OXT). Partition algorithms and logistic regression algorithms with two biomarkers (GFAP and FABP4) achieved sensitivity of 83% and 93% at 100% and 90% specificity, respectively. The strongest single marker was GFAP with an area under the ROC curve (AUC) of 0.86. The AUC for the GFAP-FABP4 combination was 0.98. CONCLUSION: PEA is a powerful new proteomic technology for biomarker discovery. GFAP and a handful of other plasma biomarkers may be useful for early glioma detection and probably, prognosis. STATEMENT: Detecting gliomas as early as possible is highly desirable since it can significantly improve the chances of effective treatments. Reliable glioma biomarkers can timely inform glioma patients about the efficacy of their prescribed treatment. Our results reveal some novel putative glioma markers that may prove valuable, when used alone or in combination, towards improved clinical care of gliomas. In order to better appreciate the potential usefulness of these markers, their performance needs to be further validated in a larger cohort of samples.

Cerebrospinal fluid camk2a levels at baseline predict long-term progression in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) remains a highly unpredictable disease. Many hope that fluid biomarkers may contribute to better stratification of disease, aiding the personalisation of treatment decisions, ultimately improving patient outcomes. OBJECTIVE: The objective of this study was to evaluate the predictive value of CSF brain-specific proteins from early in the disease course of MS on long term clinical outcomes. METHODS: In this study, 34 MS patients had their CSF collected and stored within 5 years of disease onset and were then followed clinically for at least 15 years. CSF concentrations of 64 brain-specific proteins were analyzed in the 34 patient CSF, as well as 19 age and sex-matched controls, using a targeted liquid-chromatography tandem mass spectrometry approach. RESULTS: We identified six CSF brain-specific proteins that significantly differentiated MS from controls (p < 0.05) and nine proteins that could predict disease course over the next decade. CAMK2A emerged as a biomarker candidate that could discriminate between MS and controls and could predict long-term disease progression. CONCLUSION: Targeted approaches to identify and quantify biomarkers associated with MS in the CSF may inform on long term MS outcomes. CAMK2A may be one of several candidates, warranting further exploration.

Modelling the deactivation of Escherichia coli in Nigerian soils amended with differently treated manures.

AIM: This study aimed to simulate deactivation of Escherichia coli in soils amended with cattle manure after burning, anaerobic digestion, composting, or without treatment. METHOD AND RESULTS: The Weibull survival function was used to describe deactivation of E. coli. Parameters for each treatment were determined using E. coli measurements from manure-amended soils and evaluated against measurements at different application rates. A statistically significant correlation and high coincidence between the simulated and measured values were obtained. The simulations revealed that although anaerobic digestion or burning of cattle manure effectively reduced the E. coli loads to background levels, burning retained very little nitrogen, so the ash residue was ineffective as an organic fertilizer. Anaerobic digestion was most effective at reducing E. coli levels while retaining a high proportion of N in the bioslurry residue, but the persistence of E. coli was higher than in compost. CONCLUSION: The results from this study suggest that the safest method for production of organic fertilizer would involve anaerobic digestion to reduce E. coli, followed by composting to reduce its persistence.

Impacts of different treatment methods for cattle manure on the spread of faecal indicator organisms from soil to lettuce in Nigeria.

AIM: This study investigated impacts of different organic waste treatment methods on reduction and spread of faecal indicator organisms to food crops in a developing country. METHODS AND RESULTS: Fresh cattle manure was subjected to three different treatments; anaerobic digestion, burning and composting. Escherichia coli, coliforms and nitrogen content of cattle manure were measured before and after treatment in the amended soil and harvested lettuce. All treatments significantly reduced E. coli and coliform counts but differed in the ratio of E. coli or coliforms to nitrogen. Application of the recommended nitrogen dose of 120 kg ha-1 as bioslurry resulted in significantly lower E. coli and coliform contamination of soil than the same nitrogen rate applied as compost or ash. The E. coli content of lettuces grown on soil amended with treated wastes at recommended rates did not differ between treatments but was significantly lower than in lettuces grown on soil amended with untreated manure. CONCLUSIONS: Treatment of manure before use as an organic fertilizer significantly reduces potential contamination of both soil and food crops with E. coli and coliforms. To best reduce the spread of E. coli from organic fertilizers, manures should be treated by anaerobic digestion. SIGNIFICANCE AND IMPACT OF THE STUDY: Information from this study quantifies potential risks associated with use of manures in growing food crops by determining the ratio between pathogen content and required nitrogen application rate.

An agent-based model that simulates the spatio-temporal dynamics of sources and transfer mechanisms contributing faecal indicator organisms to streams. Part 2: Application to a small agricultural catchment.

The new Model for the Agent-based simulation of Faecal Indicator Organisms (MAFIO) is applied to a small (0.42 km2) Scottish agricultural catchment to simulate the dynamics of E. coli arising from sheep and cattle farming, in order to provide a proof-of-concept. The hydrological environment for MAFIO was simulated by the "best" ensemble run of the tracer-aided ecohydrological model EcH2O-iso, obtained through multi-criteria calibration to stream discharge (MAE: 1.37 L s-1) and spatially-distributed stable isotope data (MAE: 1.14-3.02‰) for the period April-December 2017. MAFIO was then applied for the period June-August for which twice-weekly E. coli loads were quantified at up to three sites along the stream. Performance in simulating these data suggested the model has skill in capturing the transfer of faecal indicator organisms (FIOs) from livestock to streams via the processes of direct deposition, transport in overland flow and seepage from areas of degraded soil. Furthermore, its agent-based structure allowed source areas, transfer mechanisms and host animals contributing FIOs to the stream to be quantified. Such information is likely to have substantial value in the context of designing and spatially-targeting mitigation measures against impaired microbial water quality. This study also revealed, however, that avenues exist for improving process conceptualisation in MAFIO (e.g. to include FIO contributions from wildlife) and highlighted the need to quantitatively assess how uncertainty in the spatial extent of surface flow paths in the simulated hydrological environment may affect FIO simulations. Despite the consequent status of MAFIO as a research-level model, its encouraging performance in this proof-of-concept study suggests the model has significant potential for eventual incorporation into decision support frameworks.

An agent-based model that simulates the spatio-temporal dynamics of sources and transfer mechanisms contributing faecal indicator organisms to streams. Part 1: Background and model description.

A new Model for the Agent-based simulation of Faecal Indicator Organisms (MAFIO) is developed that attempts to overcome limitations in existing faecal indicator organism (FIO) models arising from coarse spatial discretisations and poorly-constrained hydrological processes. MAFIO is a spatially-distributed, process-based model presently designed to simulate the fate and transport of agents representing FIOs shed by livestock at the sub-field scale in small (<10 km2) agricultural catchments. Specifically, FIO loading, die-off, detachment, surface routing, seepage and channel routing are modelled on a regular spatial grid. Central to MAFIO is that hydrological transfer mechanisms are simulated based on a hydrological environment generated by an external model for which it is possible to robustly determine the accuracy of simulated catchment hydrological functioning. The spatially-distributed, tracer-aided ecohydrological model EcH2O-iso is highlighted as a possible hydrological environment generator. The present paper provides a rationale for and description of MAFIO, whilst a companion paper applies the model in a small agricultural catchment in Scotland to provide a proof-of-concept.

Environmental risk factors in the incidence of Johne's disease.

This review addresses the survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP), the causative pathogen of Johne's disease (JD), once it has left its ruminant host. JD has significant economic impact on dairy, beef and sheep industries and is difficult to control due to the long-term sub-clinical nature of the infection, intermittent or persistent MAP shedding during and after this period, inadequate test effectiveness, and the potential for MAP to exist for extended periods outside the host. The role that environmental factors play in the persistence and spread of MAP and consequent disease is assessed. Published risk factor analysis, organism survival across various environmental media and conditions, presence and spread in ruminant and non-ruminant wildlife, and the general potential for survival and multiplication of MAP ex-host both on and off-farm are discussed and knowledge gaps highlighted. An inclusive approach to disease management that takes into account the persistence and transport of the causative organism in on-farm soils and waters, land use and management, dispersal by domestic and non-domestic host species, as well as general animal husbandry is required on those farms where more traditional approaches to disease management have failed to reduce disease prevalence.

Criterion validity of the GMFM-66 item set and the GMFM-66 basal and ceiling approaches for estimating GMFM-66 scores.

AIM: The aim of this study was to compare the accuracy of two abbreviated approaches for estimating Gross Motor Function Measure 66 (GMFM-66) scores against the full GMFM-66 and to explore their strengths and limitations. METHOD: An existing dataset (n=224) comprising children aged 1 to 13 years (mean age 6y 11mo, SD 4y 6mo; 132 males, 92 females) with cerebral palsy (CP) of all Gross Motor Function Classification System (GMFCS) levels was used to compare the validity of the item set version (GMFM-66-IS) and the basal and ceiling version (GMFM-66-B&C) with the full GMFM-66 scores. Follow-up assessment at 1 year (n=109) allowed evaluation of change scores and accuracy at a single point in time. RESULTS: The cross-sectional agreement was excellent for both abbreviated measures (all intraclass correlation coefficients [ICCs] >0.98). When measuring change over time, both the GMFM-66-IS and the GMFM-66-B&C showed good agreement for children with bilateral CP (ICCs >0.9). However, the GMFM-66-IS assessed change over 1 year more accurately than the GMFM-66-B&C in children with unilateral CP (ICC=0.89 vs ICC=0.58; 95% confidence intervals do not overlap). INTERPRETATION: Both approaches for estimating GMFM-66 scores are accurate at a single point in time. If the primary goal of assessment is to measure change, the full GMFM-66 should still be regarded as the criterion standard. The GMFM-66-IS should be the preferred shortened measure for children with unilateral CP.

The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies.

Background: Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. Methods: To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. Results: GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. Conclusion: The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.

The Contribution of Environmental Science to Mental Health Research: A Scoping Review.

Mental health is influenced by multiple complex and interacting genetic, psychological, social, and environmental factors. As such, developing state-of-the-art mental health knowledge requires collaboration across academic disciplines, including environmental science. To assess the current contribution of environmental science to this field, a scoping review of the literature on environmental influences on mental health (including conditions of cognitive development and decline) was conducted. The review protocol was developed in consultation with experts working across mental health and environmental science. The scoping review included 202 English-language papers, published between 2010 and 2020 (prior to the COVID-19 pandemic), on environmental themes that had not already been the subject of recent systematic reviews; 26 reviews on climate change, flooding, air pollution, and urban green space were additionally considered. Studies largely focused on populations in the USA, China, or Europe and involved limited environmental science input. Environmental science research methods are primarily focused on quantitative approaches utilising secondary datasets or field data. Mental health measurement was dominated by the use of self-report psychometric scales. Measures of environmental states or exposures were often lacking in specificity (e.g., limited to the presence or absence of an environmental state). Based on the scoping review findings and our synthesis of the recent reviews, a research agenda for environmental science's future contribution to mental health scholarship is set out. This includes recommendations to expand the geographical scope and broaden the representation of different environmental science areas, improve measurement of environmental exposure, prioritise experimental and longitudinal research designs, and giving greater consideration to variation between and within communities and the mediating pathways by which environment influences mental health. There is also considerable opportunity to increase interdisciplinarity within the field via the integration of conceptual models, the inclusion of mixed methods and qualitative approaches, as well as further consideration of the socio-political context and the environmental states that can help support good mental health. The findings were used to propose a conceptual model to parse contributions and connections between environmental science and mental health to inform future studies.

Daptomycin-nonsusceptible vancomycin-intermediate staphylococcus aureus vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole.

We report two cases of daptomycin (DAP)-nonsusceptible (DNS) vancomycin-intermediate Staphylococcus aureus (VISA) vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole. Both patients responded rapidly and favorably to this combination. The clinical isolates from the two patients were tested post hoc in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model to confirm the bactericidal activity and enhancement of daptomycin and trimethoprim-sulfamethoxazole. The combination of high-dose daptomycin and trimethoprim-sulfamethoxazole should be explored further for the treatment of DNS VISA strains.

Pharmacy students' knowledge and confidence of COVID-19 following an interactive didactic class.

Background: COVID-19 education for the pharmacy workforce is important to ensure pharmacists are optimizing patient care for the prevention and management of COVID-19. However, there are currently no reports to our knowledge of education and training experiences for COVID-19 prevention and management in the Doctor of Pharmacy (PharmD) curricula. Objective: To evaluate pharmacy students' knowledge and confidence regarding COVID-19 prevention and management before and after an interactive didactic class (IDC). Methods: A multicenter, quasi-experimental, cross-sectional survey study was performed among pharmacy students before and after IDC on COVID-19 at two schools of pharmacy. The IDC on COVID-19 consisted of student-led presentations on a COVID-19 drug, an infectious disease pharmacist faculty-led interactive lecture on COVID-19 prevention and management, and clinical case vignettes to assess COVID-19 management strategies. An anonymous, voluntary, electronic survey was distributed to students (n = 85) before and after. The pre- and postintervention survey contained 10 COVID-19 knowledge-based questions and multi-step, 5-point Likert scale statements related to COVID-19 prevention and management confidence. The postintervention survey also evaluated students' perceptions of the COVID-19 IDC. Descriptive statistics were performed, and Student t test was used to compare pre- and postintervention responses. Results: About 61 surveys were completed resulting in a response rate of 72%. COVID-19 knowledge scores (mean ± SD) increased overall following the IDC (5.9 ± 1.31 vs 8.6 ± 1.29). Pharmacy students' COVID-19 confidence scores (mean ± SD) also improved following the IDC (2.66 ± 0.75 vs 4.03 ± 0.53). Students performed well on the COVID-19 clinical case vignettes with a mean ± SD score of 22.41 ± 0.46 out of 25. Pharmacy students' perceptions of the IDC on COVID-19 were also positive overall. Conclusion: Pharmacy students' knowledge and confidence of COVID-19 prevention and management improved following an IDC. This may be an effective strategy to provide COVID-19 education during the PharmD curricula.

Instruction and Simulation to Improve Pharmacy Students' Knowledge and Confidence Regarding Assessment of Penicillin Allergies.

Objective. To evaluate pharmacy students' knowledge of and confidence regarding penicillin allergy assessment and skin testing (PAAST) before and after a focused didactic instruction and simulation (FDIS).Methods. A multicenter, quasi-experimental, cross-sectional survey study was performed among pharmacy students before and after FDIS on PAAST at two schools of pharmacy. The FDIS on PAAST consisted of an infectious disease faculty-led seminar, student-led penicillin allergy counseling interviews, penicillin skin testing simulation, and case studies to assess penicillin allergy scenarios and management. An anonymous, voluntary, electronic survey was distributed to students (n=159) before and after the FDIS. The pre- and post-intervention survey contained 10 PAAST knowledge-based questions and multi-step, five-point Likert scale statements related to students' confidence in PAAST. The post-intervention survey also evaluated students' perceptions of the FDIS on PAAST. Descriptive statistics were performed, and the Student t test was used to compare pre- and post-intervention responses.Results. One hundred forty-three surveys were completed, resulting in a survey response rate of 90%. Students' PAAST knowledge scores (mean±SD) increased overall following the FDIS on PAAST (6.67±1.51 vs 7.81±1.39). Knowledge scores increased considerably for questions related to penicillin allergy consequences, cross-reactivity, and correct steps of PAAST. Pharmacy students' PAAST confidence scores (mean±SD) also improved following the interactive instruction and simulation (2.30±0.7 vs 3.22±0.67) with considerable confidence increases in penicillin skin testing. Pharmacy students' perceptions of the FDIS on PAAST were also positive overall.Conclusion. Pharmacy students' knowledge and confidence of PAAST improved following FDIS. This may be an effective strategy to implement PAAST education during pharmacy school.

The Impact of the Duration of Antibiotic Therapy in Patients With Community-Onset Pneumonia on Readmission Rates: A Retrospective Cohort Study.

BACKGROUND: Recent publications have confirmed that 70% of hospitalized adults with uncomplicated community-acquired pneumonia and health-care-associated pneumonia are prescribed a duration therapy that exceeds current guideline recommendations. OBJECTIVE: The primary objective is to evaluate the relationship between antibiotic duration and all-cause 30-day readmission rates. Secondary outcomes include pneumonia-specific 30-day readmission rate and identification of risk factors for readmission. METHODS: Patients aged ≥18 years with a primary diagnosis of pneumonia from January 1, 2016, to December 31, 2016, were included in this single-center, retrospective cohort study. Patients were categorized by antibiotic therapy duration of ≤7 days (n = 139) or >7 days (n = 286), and outcomes were analyzed in both bivariate and multivariate models. A multivariate logistic regression was used to assess the relationship between all-cause 30-day readmission and antibiotic days. RESULTS: Baseline characteristics were not significantly different between the 2 groups. All-cause 30-day readmission rates were 15.8% and 15.5% for patients who received ≤7 days versus >7 days of antibiotics, respectively (P = .95). Pneumonia-specific 30-day readmission occurred in 3.6% of patients who received antibiotics for ≤7 days compared to 3.5% of patients who received antibiotics for >7 days (P = .95). Multivariate logistic regression showed no statistically significant association between readmission rate and antibiotic duration of >7 days. Statistically significant risk factors for readmission identified by logistic regression include ≥3 hospital admissions within the previous year, a hematocrit <30% at discharge, a history of chronic obstructive pulmonary disorder (COPD), and weight. CONCLUSION: The use of prolonged antibiotic therapy for the treatment of community-onset pneumonia was not associated with a decrease in all-cause or pneumonia-specific 30-day readmission rates.

Development and validation of item sets to improve efficiency of administration of the 66-item Gross Motor Function Measure in children with cerebral palsy.

AIM: To develop an algorithmic approach to identify item sets of the 66-item version of the Gross Motor Function Measure (GMFM-66) to be administered to individual children, and to examine the validity of the algorithm for obtaining a GMFM-66 score. METHOD: An algorithmic approach was used to identify item sets of the GMFM-66 (GMFM-66-IS) using data from 95 males and 79 females with cerebral palsy (CP; mean age 14y 7mo, SD 1y 8mo, range 12y 7mo to 17y 8mo). The GMFM-66-IS scores were then validated using combined data from three Dutch studies involving 134 males and 92 females with CP (mean age 7y, SD 4y 6mo, range 1y 4mo to 13y 8mo), representing all levels of the Gross Motor Function Classification System. RESULTS: The final algorithm contains three decision items from the GMFM-66 that determine which one of four item sets to administer. The GMFM-66-IS has excellent agreement with the full GMFM-66 both at a single assessment (intraclass correlation coefficient [ICC]=0.994, 95% confidence intervals [CI] 0.993-0.996) and across repeat assessments (ICC=0.92, 95% CI 0.89-0.95). INTERPRETATION: The GMFM-66-IS is a promising alternative to the full GMFM-66. Users should be consistent in their choice of measure (GMFM-66 or GMFM-66-IS) on repeat testing and clearly identify which method was used.

Penicillin Allergy Assessment and Skin Testing in the Outpatient Setting.

Penicillin allergies are among of the most commonly reported allergies, yet only 10% of these patients are truly allergic. This leads to potential inadvertent negative consequences for patients and makes treatment decisions challenging for clinicians. Thus, allergy assessment and penicillin skin testing (PST) are important management strategies to reconcile and clarify labeled penicillin allergies. While PST is more common in the inpatient setting where the results will immediately impact antibiotic management, this process is becoming of increasing importance in the outpatient setting. PST in the outpatient setting allows clinicians to proactively de-label and educate patients accordingly so beta-lactam antibiotics may be appropriately prescribed when necessary for future infections. While allergists have primarily been responsible for PST in the outpatient setting, there is an increasing role for pharmacist involvement in the process. This review highlights the importance of penicillin allergy assessments, considerations for PST in the outpatient setting, education and advocacy for patients and clinicians, and the pharmacist's role in outpatient PST.

Assessing Risk of E. coli Resuspension from Intertidal Estuarine Sediments: Implications for Water Quality.

Estuarine sediments are a reservoir for faecal bacteria, such as E. coli, where they reside at greater concentrations and for longer periods than in the overlying water. Faecal bacteria in sediments do not usually pose significant risk to human health until resuspended into the water column, where transmission routes to humans are facilitated. The erosion resistance and corresponding E. coli loading of intertidal estuarine sediments was monitored in two Scottish estuaries to identify sediments that posed a risk of resuspending large amounts of E. coli. In addition, models were constructed in an attempt to identify sediment characteristics leading to higher erosion resistance. Sediments that exhibited low erosion resistance and a high E. coli loading occurred in the upper- and mid-reaches of the estuaries where sediments had higher organic content and smaller particle sizes, and arose predominantly during winter and autumn, with some incidences during summer. Models using sediment characteristics explained 57.2% and 35.7% of sediment shear strength and surface stability variance respectively, with organic matter content and season being important factors for both. However large proportions of the variance remained unexplained. Sediments that posed a risk of resuspending high amounts of faecal bacteria could be characterised by season and sediment type, and this should be considered in the future modelling of bathing water quality.

Factors affecting the spatial and temporal distribution of E. coli in intertidal estuarine sediments.

Microbiological water quality monitoring of bathing waters does not account for faecal indicator organisms in sediments. Intertidal deposits are a significant reservoir of FIOs and this indicates there is a substantial risk to bathers through direct contact with the sediment, or through the resuspension of bacteria to the water column. Recent modelling efforts include sediment as a secondary source of contamination, however, little is known about the driving factors behind spatial and temporal variation in FIO abundance. E. coli abundance, in conjunction with a wide range of measured variables, was used to construct models to explain E. coli abundance in intertidal sediments in two Scottish estuaries. E. coli concentrations up to 6 log10 CFU 100 g dry wt-1 were observed, with optimal models accounting for E. coli variation up to an adjusted R2 of 0.66. Introducing more complex models resulted in overfitting of models, detrimentally affected the transferability of models between datasets. Salinity was the most important single variable, with season, pH, colloidal carbohydrates, organic content, bulk density and maximum air temperature also featuring in optimal models. Transfer of models, using only lower cost variables, between systems explained an average deviance of 42%. This study demonstrates the potential for cost-effective sediment characteristic monitoring to contribute to FIO fate and transport modelling and consequently the risk assessment of bathing water safety.