Assessment of the occurrence and potential risks of antibiotics and their metabolites in South Florida waters using liquid chromatography tandem mass spectrometry

An automated on-line SPE-LC-MS/MS method was developed for the quantitation of multiple classes of antibiotics in environmental waters. High sensitivity in the low ng/L range was accomplished by using large volume injections with 10-mL of sample. Positive confirmation of analytes was achieved using two selected reaction monitoring (SRM) transitions per antibiotic and quantitation was performed using an internal standard approach. Samples were extracted using online solid phase extraction, then using column switching technique; extracted samples were immediately passed through liquid chromatography and analyzed by tandem mass spectrometry. The total run time per each sample was 20 min. The statistically calculated method detection limits for various environmental samples were between 1.2 and 63 ng/L. Furthermore, the method was validated in terms of precision, accuracy and linearity. ^ The developed analytical methodology was used to measure the occurrence of antibiotics in reclaimed waters (n=56), surface waters (n=53), ground waters (n=8) and drinking waters (n=54) collected from different parts of South Florida. In reclaimed waters, the most frequently detected antibiotics were nalidixic acid, erythromycin, clarithromycin, azithromycin trimethoprim, sulfamethoxazole and ofloxacin (19.3-604.9 ng/L). Detection of antibiotics in reclaimed waters indicates that they can't be completely removed by conventional wastewater treatment process. Furthermore, the average mass loads of antibiotics released into the local environment through reclaimed water were estimated as 0.248 Kg/day. Among the surface waters samples, Miami River (reaching up to 580 ng/L) and Black Creek canal (up to 124 ng/L) showed highest concentrations of antibiotics. No traces of antibiotics were found in ground waters. On the other hand, erythromycin (monitored as anhydro erythromycin) was detected in 82% of the drinking water samples (n.d-66 ng/L). The developed approach is suitable for both research and monitoring applications.^ Major metabolites of antibiotics in reclaimed wates were identified and quantified using high resolution benchtop Q-Exactive orbitrap mass spectrometer. A phase I metabolite of erythromycin was tentatively identified in full scan based on accurate mass measurement. Using extracted ion chromatogram (XIC), high resolution data-dependent MS/MS spectra and metabolic profiling software the metabolite was identified as desmethyl anhydro erythromycin with molecular formula C36H63NO12 and m/z 702.4423. The molar concentration of the metabolite to erythromycin was in the order of 13 %. To my knowledge, this is the first known report on this metabolite in reclaimed water. Another compound acetyl-sulfamethoxazole, a phase II metabolite of sulfamethoxazole was also identified in reclaimed water and mole fraction of the metabolite represent 36 %, of the cumulative sulfamethoxazole concentration. The results were illustrating the importance to include metabolites also in the routine analysis to obtain a mass balance for better understanding of the occurrence, fate and distribution of antibiotics in the environment. ^ Finally, all the antibiotics detected in reclaimed and surface waters were investigated to assess the potential risk to the aquatic organisms. The surface water antibiotic concentrations that represented the real time exposure conditions revealed that the macrolide antibiotics, erythromycin, clarithromycin and tylosin along with quinolone antibiotic, ciprofloxacin were suspected to induce high toxicity to aquatic biota. Preliminary results showing that, among the antibiotic groups tested, macrolides posed the highest ecological threat, and therefore, they may need to be further evaluated with, long-term exposure studies considering bioaccumulation factors and more number of species selected. Overall, the occurrence of antibiotics in aquatic environment is posing an ecological health concern.^

Combined effects of short-term exposure to elevated CO2 and decreased O2 on the physiology and energy budget of the thick shell mussel Mytilus coruscus

Hypoxia and ocean acidification are two consequences of anthropogenic activities. These global trends occur on top of natural variability. In environments such as estuarine areas, short-term acute pH and O2 fluctuations are occurring simultaneously. The present study tested the combined effects of short-term seawater acidification and hypoxia on the physiology and energy budget of the thick shell mussel Mytilus coruscus. Mussels were exposed for 72 h to six combined treatments with three pH levels (8.1, 7.7 and 7.3) and two dissolved oxygen (DO) levels (2 mg/L, 6 mg/L). Clearance rate (CR), food absorption efficiency (AE), respiration rate (RR), ammonium excretion rate (ER), O:N ratio and scope for growth (SFG) were significantly reduced, and faecal organic dry weight ratio (E) was significantly increased at low DO. Low pH did not lead to a reduced SFG. Interactive effects of pH and DO were observed for CR, E and RR. Principal component analysis (PCA) revealed positive relationships among most physiological indicators, especially between SFG and CR under normal DO conditions. These results demonstrate that Mytilus coruscus was sensitive to short-term (72 h) exposure to decreased O2 especially if combined with decreased pH levels. In conclusion, the short-term oxygen and pH variation significantly induced physiological changes of mussels with some interactive effects.

Short-term temporal and spatial variations in physical, optical and biogeochemical parameters in June of 2013 in Alfacs Bay (NW Mediterranean)

With the aim of analyzing the complex physical and biogeochemical interactions at high temporal and spatial resolution in the complex estuarine waters of Alfacs Bay, a beam attenuation-based approach was used as optical proxy of different biogeochemical variables. Thus, the dataset contains the attenuation proxies as well as laboratory results from the analysis of water samples, which were used to validate our approach. In addition, the major physical forcing in the Bay was also measured.

The effects of graded levels of calorie restriction : V. Impact of short term calorie and protein restriction on physical activity in the C57BL/6 mouse

Peer reviewed

Effect of enhanced pCO2 levels on the production of dissolved organic carbon and transparent exopolymer particles in short-term bioassay experiments

It has been proposed that increasing levels of pCO2 in the surface ocean will lead to more partitioning of the organic carbon fixed by marine primary production into the dissolved rather than the particulate fraction. This process may result in enhanced accumulation of dissolved organic carbon (DOC) in the surface ocean and/or concurrent accumulation of transparent exopolymer particles (TEPs), with important implications for the functioning of the marine carbon cycle. We investigated this in shipboard bioassay experiments that considered the effect of four different pCO2 scenarios (ambient, 550, 750 and 1000 µatm) on unamended natural phytoplankton communities from a range of locations in the northwest European shelf seas. The environmental settings, in terms of nutrient availability, phytoplankton community structure and growth conditions, varied considerably between locations. We did not observe any strong or consistent effect of pCO2 on DOC production. There was a significant but highly variable effect of pCO2 on the production of TEPs. In three of the five experiments, variation of TEP production between pCO2 treatments was caused by the effect of pCO2 on phytoplankton growth rather than a direct effect on TEP production. In one of the five experiments, there was evidence of enhanced TEP production at high pCO2 (twice as much production over the 96 h incubation period in the 750 ?atm treatment compared with the ambient treatment) independent of indirect effects, as hypothesised by previous studies. Our results suggest that the environmental setting of experiments (community structure, nutrient availability and occurrence of phytoplankton growth) is a key factor determining the TEP response to pCO2 perturbations.

Short and Long Term Representation of an Unfamiliar Tone Distribution

We report on a study conducted to extend our knowledge about the process of gaining a mental representation of music. Several studies, inspired by research on the statistical learning of language, have investigated statistical learning of sequential rules underlying tone sequences. Given that the mental representation of music correlates with distributional properties of music, we tested whether participants are able to abstract distributional information contained in tone sequences to form a mental representation. For this purpose, we created an unfamiliar music genre defined by an underlying tone distribution, to which 40 participants were exposed. Our stimuli allowed us to differentiate between sensitivity to the distributional properties contained in test stimuli and long term representation of the distributional properties of the music genre overall. Using a probe tone paradigm and a two-alternative forced choice discrimination task, we show that listeners are able to abstract distributional properties of music through mere exposure into a long term representation of music. This lends support to the idea that statistical learning is involved in the process of gaining musical knowledge.

ARB: Phase II window of opportunity study of short-term preoperative treatment with enzalutamide in ER-positive and triple-negative breast cancer

The androgen receptor (AR) is expressed in 60-80% of breast cancers (BC) across all molecular phenotypes, with a higher incidence in oestrogen receptor positive (ER+) BC compared to ER negative tumours. In ER+ disease, AR-expression has been linked to endocrine resistance which might be reversed with combined treatment targeting ER and AR. In triple negative BCs (TNBC), preclinical and clinical investigations have described a subset of patients that express the AR and are sensitive to androgen blockade, providing a novel therapeutic target. Enzalutamide, a potent 2nd generation anti-androgen, has demonstrated substantial preclinical and clinical anti-tumour activity in AR+ breast cancer. Short-term preoperative window of opportunity studies are a validated strategy for novel treatments to provide proof-of-concept and define the most appropriate patient population by directly assessing treatment effects in tumour tissue before and after treatment. The ARB study aims to assess the anti-tumour effects of enzalutamide in early ER+ breast cancer and TNBC, to identify the optimal target population for further studies and to directly explore the biologic effects of enzalutamide on BC and stromal cells. Methods: ARB is an international, investigator sponsored WOO phase II study in women with newly diagnosed primary ER+ BC or AR+ TNBC of ≥ 1cm. The study has two cohorts. In the ER+ cohort, postmenopausal patients will be randomised 2:1 to receive either enzalutamide (160mg OD) plus exemestane (50mg OD) or exemestane (25mg OD). In the TNBC cohort, AR+ will receive single agent treatment with enzalutamide (160mg OD). Study treatment is planned for 15–29 days, followed by surgery or neo-adjuvant therapy. Tissue and blood samples are collected before treatment and on the last day of study treatment. The primary endpoint is inhibition of tumour-cell proliferation, as measured by change in Ki67 expression, determined centrally by 2 investigators. Secondary endpoints include induction of apoptosis (Caspase3), circulating hormone levels and safety. ARB aims to recruit ≈235 patients from ≈40 sites in the UK, Germany, Spain and USA. The study is open to recruitment.

Towards a Better Modelling and Assessment of Construction Risk: Insights from a Literature Review

This paper reviews the literature of construction risk modelling and assessment. It also reviews the real practice of risk assessment. The review resulted in significant results, summarised as follows. There has been a major shift in risk perception from an estimation variance into a project attribute. Although the Probability–Impact risk model is prevailing, substantial efforts are being put to improving it reflecting the increasing complexity of construction projects. The literature lacks a comprehensive assessment approach capable of capturing risk impact on different project objectives. Obtaining a realistic project risk level demands an effective mechanism for aggregating individual risk assessments. The various assessment tools suffer from low take-up; professionals typically rely on their experience. It is concluded that a simple analytical tool that uses risk cost as a common scale and utilises professional experience could be a viable option to facilitate closing the gap between theory and practice of risk assessment.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013

Global, regional, and national comparative risk assessment of 79 behavioral, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015 : a systematic analysis for the Global Burden of Disease Study 2015

Performance of protective factors assessment in risk prediction for adults: systematic review and meta-analysis

Protective factors are neglected in risk assessment in adult psychiatric and criminal justice populations. This review investigated the predictive efficacy of selected tools that assess protective factors. Five databases were searched using comprehensive terms for records up to June 2014, resulting in 17 studies (n = 2,198). Results were combined in a multilevel meta-analysis using the R (R Core Team, R: A Language and Environment for Statistical Computing, Vienna, Austria: R Foundation for Statistical Computing, 2015) metafor package (Viechtbauer, Journal of Statistical Software, 2010, 36, 1). Prediction of outcomes was poor relative to a reference category of violent offending, with the exception of prediction of discharge from secure units. There were no significant differences between the predictive efficacy of risk scales, protective scales, and summary judgments. Protective factor assessment may be clinically useful, but more development is required. Claims that use of these tools is therapeutically beneficial require testing.

DYNAMICS OF THE SHORT TERM AND LONG TERM AVIAN DISTRIBUTIONS IN NORTH AMERICA - THE ROLES OF VEGETATION HEIGHT HETEROGENEITY AND CLIMATIC FACTORS

Understanding how biodiversity spatially distribute over both the short term and long term, and what factors are affecting the distribution, are critical for modeling the spatial pattern of biodiversity as well as for promoting effective conservation planning and practices. This dissertation aims to examine factors that influence short-term and long-term avian distribution from the geographical sciences perspective. The research develops landscape level habitat metrics to characterize forest height heterogeneity and examines their efficacies in modelling avian richness at the continental scale. Two types of novel vegetation-height-structured habitat metrics are created based on second order texture algorithms and the concepts of patch-based habitat metrics. I correlate the height-structured metrics with the richness of different forest guilds, and also examine their efficacies in multivariate richness models. The results suggest that height heterogeneity, beyond canopy height alone, supplements habitat characterization and richness models of two forest bird guilds. The metrics and models derived in this study demonstrate practical examples of utilizing three-dimensional vegetation data for improved characterization of spatial patterns in species richness. The second and the third projects focus on analyzing centroids of avian distributions, and testing hypotheses regarding the direction and speed of these shifts. I first showcase the usefulness of centroids analysis for characterizing the distribution changes of a few case study species. Applying the centroid method on 57 permanent resident bird species, I show that multi-directional distribution shifts occurred in large number of studied species. I also demonstrate, plain birds are not shifting their distribution faster than mountain birds, contrary to the prediction based on climate change velocity hypothesis. By modelling the abundance change rate at regional level, I show that extreme climate events and precipitation measures associate closely with some of the long-term distribution shifts. This dissertation improves our understanding on bird habitat characterization for species richness modelling, and expands our knowledge on how avian populations shifted their ranges in North America responding to changing environments in the past four decades. The results provide an important scientific foundation for more accurate predictive species distribution modeling in future.

A comparison of neck bending and flexion measurement methods for assessment of ergonomic risk

International audience

Gender, Behavioral Assessment of Negative Reinforcement Driven Risk Taking Propensity, and Cigarette Smoking

Cigarette smoking remains the leading preventable cause of death and disability in the United States and most often is initiated during adolescence. An emerging body of research suggests that a negative reinforcement model may explain factors that contribute to tobacco use during adolescence and that negative reinforcement processes may contribute to tobacco use to a greater extent among female adolescents than among male adolescents. However, the extant literature both on the relationship between negative reinforcement processes and adolescent tobacco use as well as on the relationship between gender, negative reinforcement processes, and adolescent tobacco use is limited by the sole reliance on self-report measures of negative reinforcement processes that may contribute to cigarette smoking. The current study aimed to further disentangle the relationships between negative reinforcement based risk taking, gender and tobacco use during older adolescence by utilizing a behavioral analogue measure of negative reinforcement based risk taking, the Maryland Resource for the Behavioral Utilization of the Reinforcement of Negative Stimuli (MRBURNS). Specifically, we examined the relationship between pumps on the MRBURNS, an indicator of risk taking, and smoking status as well as the interaction between MRBURNS pumps and gender for predicting smoking status. Participants included 103 older adolescents (n=51 smokers, 50.5% female, Age (M(SD) = 19.41(1.06)) who all attended one experimental session during which they completed the MRBURNS as well as self-report measures of tobacco use, nicotine dependence, alcohol use, depression, and anxiety. We utilized binary logistic regressions to examine the relationship between MRBURNS pumps and smoking status as well as the interactive effect of MRBURNS pumps and gender for predicting smoking status. Controlling for relevant covariates, pumps on the MRBURNS did not significantly predict smoking status and the interaction between pumps on the MRBURNS and gender also did not significantly predict smoking status. These findings highlight the importance of future research examining various task modifications to the MRBURNS as well as the need for replications of this study with larger, more diverse samples.