53 research outputs found

    Development and Application of Suspect and Nontarget Screening to Characterize Organic Micropollutants in Aquatic Environments of New York State

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    Organic micropollutants (OMPs) have presented a global challenge to water resources management due to concerns over their adverse impacts on aquatic biota and human health at low exposure concentrations (e.g., at ng/L to μg/L levels in aquatic systems). OMPs encompass an extensive array of synthetic organic compounds (e.g., pharmaceuticals, pesticides, personal care products, household chemicals, industrial additives) and their transformation products. My research has been centered around establishing analytical methods based on liquid chromatography-high-resolution mass spectrometry (LC-HRMS), with a focus on the development and application of suspect and nontarget screening workflows for the identification and prioritization of OMPs in inland lakes, streams, and urban wastewater in New York State. In Chapter 1, I collaborated with volunteers from the Citizens Statewide Lake Assessment Program and scientists at the Upstate Freshwater Institute to conduct the first statewide investigation of OMP occurrence in New York inland lakes. Through this project, I developed a suspect screening method based on LC-HRMS to identify and quantify 65 OMPs in 314 lake water samples collected by volunteers from 111 lakes, ponds, and reservoirs across the state. I also performed partial least squares regression and multiple linear regression analyses to prioritize total dissolved nitrogen, specific conductance, and a wastewater-derived fluorescent organic matter component as the best combination of explanatory predictors for the inter-lake variability in OMP occurrence patterns. I further applied the exposure-activity ratio approach to estimate the potential for biological effects associated with OMPs. My work demonstrated that engaging an established network of citizen volunteers offers a viable approach to increasing the spatiotemporal coverage of OMP monitoring while raising public awareness of their prevalence. In Chapter 2, I collaborated with Drs. Christa Kelleher and Rebecca Schewe to investigate the occurrence patterns of OMPs in streams draining mixed-use watersheds in central New York. I combined the use of polar organic chemical integrative samplers (POCIS) with suspect screening and nontarget screening based on LC-HRMS to identify and quantify 133 OMPs in samples collected from 20 stream sites over two sampling seasons. I also performed hierarchical clustering to establish the co-occurrence profiles of OMPs in connection with watershed attributes indicative of anthropogenic influences. I further evaluated the feasibility of deploying POCIS for estimating daily average loads of OMPs and their potential for biological effects in streams via screening-level risk assessments. My work supported the prospect of combining passive sampling with high-resolution accurate mass screening for the multi-watershed characterization of OMP contamination status in streams. In Chapter 3, I collaborated with colleagues from the School of Public Health to pursue one of the earliest wastewater-based epidemiology studies on population-level substance use during the COVID-19 pandemic. I developed and validated an online solid-phase extraction method for sample preconcentration before LC-HRMS analyses to achieve rapid screening of health and lifestyle-related substances in urban wastewater. I applied this method to quantify the levels of 26 pharmaceuticals and lifestyle chemicals in wastewater influent samples collected from six sewersheds in central New York over a period spanning the rising and falling of COVID-19 prevalence. I back-calculated the population-level consumption rates of antidepressants, antiepileptics, antihistamines, antihypertensives, and central nervous system stimulants and further identified their co-variation with disparities in household income, marital status, and/or age of the contributing populations as well as the detection frequency of SARS-CoV-2 RNA in wastewater and the COVID-19 test positivity within the sewersheds. My work highlighted the utility of high-throughput wastewater analysis for assessing substance use patterns during a public health crisis such as COVID-19

    PFAS: forever chemicals — persistent, bioaccumulative and mobile: reviewing the status and the need for their phase out and remediation of contaminated sites

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    Background Per- and polyfluorinated alkyl substances (PFAS) have received increasing scientific and political attention in recent years. Several thousand commercially produced compounds are used in numerous products and technical processes. Due to their extreme persistence in the environment, humans and all other life forms are, therefore, increasingly exposed to these substances. In the following review, PFAS will be examined comprehensively. Results The best studied PFAS are carboxylic and sulfonic acids with chain lengths of C4 to C14, particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). These substances are harmful to aquatic fauna, insects, and amphibians at concentrations of a few µg/L or less, accumulate in organisms, and biomagnify in food webs. Humans, as the final link in numerous food chains, are subjected to PFAS uptake primarily through food and drinking water. Several PFAS have multiple toxic effects, particularly affecting liver, kidney, thyroid, and the immune system. The latter effect is the basis for the establishment of a tolerable weekly dose of only 4.4 ng/kg body weight for the sum of the four representatives PFOA, PFOS, perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) by the European Food Safety Authority (EFSA) in 2020. Exposure estimates and human biomonitoring show that this value is frequently reached, and in many cases exceeded. PFAS are a major challenge for analysis, especially of products and waste: single-substance analyses capture only a fragment of the large, diverse family of PFAS. As a consequence, sum parameters have gained increasing importance. The high mobility of per and polyfluorinated carboxylic and sulfonic acids makes soil and groundwater pollution at contaminated sites a problem. In general, short-chain PFAS are more mobile than long-chain ones. Processes for soil and groundwater purification and drinking water treatment are often ineffective and expensive. Recycling of PFAS-containing products such as paper and food packaging leads to carryover of the contaminants. Incineration requires high temperatures to completely destroy PFAS. After PFOA, PFOS and a few other perfluorinated carboxylic and sulfonic acids were regulated internationally, many manufacturers and users switched to other PFAS: short-chain representatives, per- and polyfluorinated oxo carboxylic acids, telomeric alcohols and acids. Analytical studies show an increase in environmental concentrations of these chemicals. Ultra-short PFAS (chain length C1–C3) have not been well studied. Among others, trifluoroacetic acid (TFA) is present globally in rapidly increasing concentrations. Conclusions The substitution of individual PFAS recognized as hazardous by other possibly equally hazardous PFAS with virtually unknown chronic toxicity can, therefore, not be a solution. The only answer is a switch to fluorine-free alternatives for all applications in which PFAS are not essential

    An Evaluation of Medication Safety related Communications in the Patient Healthcare Pathway in Kuwait

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    Background: Patient safety is a recognised public health issue. When post-market medication safety information emerges, the benefits and risks of the medication concerned are usually evaluated by drug regulatory agencies. The outcomes of such pharmacovigilance activities are communicated to the public, patients and other healthcare professionals (HCPs). The aim of these medication safety communications might vary from improving the intended recipients’ knowledge or attitudes to outlining specific actions to be followed by them. However, it is currently recognised that sharing medication-related information does not improve patients’ safety on its own if not accompanied by an accurate implementation of these recommendations in clinical practice. Despite their importance in protecting patient safety and subsequently affecting public health, no previous study was found to have evaluated or described the process of creating and disseminating medication safety communications by the Kuwaiti drug regulatory agency. Equally, no study was found to have investigated the impact of or the factors affecting the implementation of regulatory-related medication safety communications in Kuwait. Therefore, this thesis aimed to address these gaps in knowledge by evaluating medication safety communications in the patient healthcare pathway in Kuwait. Methods: This multiphase study was preceded by a systematic literature review of the factors affecting HCPs’ implementation of regulatory-related medication safety communications, using a narrative synthesis approach. Following the systematic review, multiphase research was initiated. This consisted of three phases, each of which focused on a specific stakeholder group involved in the process of medication safety communication. Phase 1 involved Kuwait Drug and Food Control (KDFC), an administration within the Ministry of Health (MOH), as the regulatory agency responsible for pharmacovigilance activities. This was a convergent mixed-methods study. Data collection in this phase included documents produced by KDFC or issued to KDFC relating to medication safety and three face-to-face interviews with KDFC employees involved in pharmacovigilance activities. Documents were analysed using a descriptive quantitative approach and a framework analysis technique. Phase 2 focused on healthcare professionals working in MOH hospitals in Kuwait. This phase was an exploratory mixed-methods study, where focus group discussions were conducted followed by the distribution of an online survey. The focus group discussions were analysed using a thematic analysis technique. In the second part of this phase, an online survey was developed based on Phase 1, the focus group discussions and the systematic literature review. Survey data analysis included descriptive analysis (frequency and percentile) and statistical analysis including principal component analysis (PCA) and the Kruskal–Wallis H test, which was followed by a post hoc analysis of variables that had significant results. Other statistical tests applied included Fisher’s exact test, the Mann–Whitney U Test, and multivariate regression analysis. Participants’ answers to open-ended survey questions were analysed using a conventional content analysis technique. Phase 3 was an interpretive phenomenology study. This phase involved semi-structured phone interviews with six female patients of childbearing age who used a valproate-related medication for epilepsy or migraine. These patients had been prescribed the valproate-related medication in one of six secondary hospitals and one specialist neurology hospital within the MOH hospitals. An interpretive phenomenological analysis technique was applied to analyse the transcripts. Results: The results of the systematic literature review indicated that the factors affecting HCPs’ implementation of medication safety communications occur at multiple levels. These levels included the sources or senders of the safety information (delays in the delivery of medications safety communications), healthcare institutions (hospitals’ position and interpretations of the recommendations), the HCPs (knowledge of the content of medications safety communications), and the patients and/or their carers (willingness to use the medication concerned). Phase 1 revealed a lack of legislation and a pharmacovigilance-specific policy. Results from Phase 2 reflected poor knowledge of the concept of medication safety communications within the context of pharmacovigilance and a lack of familiarity with the tools used by KDFC to communicate emerging medication information among HCPs. In the survey, although the majority of HCPs who responded were aware of the teratogenicity of VRM (65.1%, (n = 110/169)), only 2.6% had responded correctly to the statements of the VRM KDFC recommendations. More than half of the participants (57%) reported changing their practice to accommodate at least one intended KDFC recommendation. Providing female patients with written information (37.2%) and counselling female patients about contraceptive use (37.2%) were the most reported intended changes in practice. The most reported barriers to implementation included not having the capacity in terms of time and/or the infrastructure to implement the recommendations (33.8%). Four themes originating from patient interviews included (1) the timeline of the patient’s experience (2) varied knowledge and perception with valproate use, (3) patient’s expectations from HCPs and (4) experiences and preferences towards medication safety communications. Conclusion: Medication safety communications are essential tools for disseminating information related to medication safety updates to HCPs, patients and the public. This research identified challenges at the level of the sender (KDFC) and the intended recipients (HCPs and patients) that could reduce the ability of KDFC’s medication safety communications to reach clinical practices. The first step in increasing their reach is to adapt electronic methods for disseminating such information. Involving stakeholders, such as HCPs and patients, in evaluating the clarity and understandability of KDFC’s medication safety communications should be the focus of future research

    Cheminformatics and Computational Approaches for Identifying and Managing Unknown Chemicals in the Environment

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    In most societies, using chemical products has become a part of daily life. Worldwide, over 350,000 chemicals have been registered for use in e.g., daily household consumption, industrial processes, agriculture, etc. However, despite the benefits chemicals may bring to society, their usage, production, and disposal, which leads to their eventual release into the environment has multiple implications. Anthropogenic chemicals have been detected in myriad ecosystems all over the planet, as well as in the tissues of wildlife and humans. The potential consequences of such chemical pollution are not fully understood, but links to the onset of human disease and threats to biodiversity have been attributed to the presence of chemicals in our environment. Mitigating the potential negative effects of chemicals typically involves regulatory steps and multiple stakeholders. One key aspect thereof is environmental monitoring, which consists of environmental sampling, measurement, data analysis, and reporting. In recent years, advancements in Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), open chemical databases, and software have enabled researchers to identify known (e.g., pesticides) as well as unknown environmental chemicals, commonly referred to as suspect or non-target compounds. However, identifying unknown chemicals, particularly non-targets, remains extremely challenging because of the lack of a priori knowledge on the analytes - all that is available are their mass spectrometry signals. In fact, the number of unknown features in a typical mass spectrum of an environmental sample is in the range of thousands to tens of thousands, and therefore requires feature prioritisation before identification within a suitable workflow. In this dissertation work, collaborations with two regulatory authorities responsible for environmental monitoring sought to identify relevant unknown compounds in the environment, specifically by developing computational workflows for unknown identification in LC-HRMS data. The first collaboration culminated in Publication A, which involved a joint project with the Zürcher Amt für Wasser, Energie und Luft. Environmental samples taken from wastewater treatment plant sites in Switzerland were retrospectively analysed using a pre-screening workflow that prioritised features suitable for non-target identification. For this purpose, a multi-step Quality Control algorithm that checks the quality of mass spectral data in terms of peak intensities, alignment, and signal-to-noise ratio was developed and used within pre-screening. This algorithm was incorporated into the R package Shinyscreen. Features that were prioritised by pre-screening then underwent identification using the in silico fragmentation tool MetFrag. To obtain these identifications, MetFrag was coupled to various open chemical information resources such as spectral databases like MassBank Europe and MassBank of North America, as well as suspect lists from the NORMAN Suspect List Exchange and the CompTox Chemicals Dashboard database. One confirmed and twenty-one tentative compound identifications were achieved and reported according to an established confidence level scheme. Comprehensive data interpretation and detailed communication of MetFrag’s results was performed as a means of formulating evidence-based recommendations that may inform future environmental monitoring campaigns. Building on the pre-screening and identification workflow developed in Publication A, Publication B resulted from a collaboration with the Luxembourgish Administration de la gestion de l’eau that sought to identify, and where possible quantify unknown chemicals in Luxembourgish surface waters. More specifically, surface water samples collected as part of a two-year national monitoring campaign were measured using LC-HRMS and screened for pharmaceutical parent compounds and their transformation products. Compared to pharmaceutical compound information, which is publicly available from local authorities (and was used in the suspect list), information on transformation products is relatively scarce. Therefore, new approaches were developed in this work to mine data from the PubChem database as well as from the literature in order to formulate a suspect list containing pharmaceutical transformation products, in addition to their parent compounds. Overall, 94 pharmaceuticals and 14 transformation products were identified, of which 88 and 2 were confirmed identifications respectively. The spatio-temporal occurrence and distribution of these compounds throughout the Luxembourgish environment were analysed using advanced data visualisations that highlighted patterns in certain regions and time periods of high incidence. These findings may support future chemicals management measures, particularly in environmental monitoring. Another challenging aspect of managing chemicals is that they mostly exist as complex mixtures within the environment as well as chemical products. Substances of Unknown or Variable composition, Complex reaction products or Biological materials (UVCBs) make up 20-40% of international chemical registries and include chlorinated paraffins, polymer mixtures, petroleum fractions, and essential oils. However, little is known about their chemical identities and/or compositions, which poses formidable obstacles to assessing their environmental fate and toxicity, let alone identification in the environment. Publication C addresses the challenges of UVCBs by taking an interdisciplinary approach in reviewing the literature that incorporates considerations of their chemical representations, toxicity, environmental fate, exposure, and regulatory approaches. Improved substance registration requirements, grouping techniques to simplify assessment, and the use of Mixture InChI to represent UVCBs in a findable, accessible, interoperable, and reusable (FAIR) way in databases are amongst the key recommendations of this work. A specific type of UVCB, mixtures of homologous compounds, are commonly detected in environmental samples, including many High Production Volume (HPV) compounds such as surfactants. Compounds forming homologous series are related by a common core fragment and repeating chemical subunit, and can be represented using general formulae (e.g., CnF2n+1COOH) and/or Markush structures. However, a significant identification bottleneck is the inability to match their characteristic analytical signals in LC-HRMS data with chemicals in databases; while comb-like elution patterns and constant differences in mass-to-charge ratio indicate the presence of homologous series in samples, most chemical databases do not contain annotated homologous series. To address this gap, Publication D introduces a cheminformatics algorithm, OngLai, to detect homologous series within compound datasets. OngLai, openly implemented in Python using the RDKit, detects homologous series based on two inputs: a list of compounds and the chemical structure of a repeating unit. OngLai was applied to three open datasets from environmental chemistry, exposomics, and natural products, in which thousands of homologous series with a CH2 repeating unit were detected. Classification of homologous series in compound datasets is expected to advance their analytical detection in samples. Overall, the work in this dissertation contributed to the advancement of identifying and managing unknown chemicals in the environment using cheminformatics and computational approaches. All work conducted followed Open Science and FAIR data principles: all code, datasets, analyses, and results generated, including the final peer-reviewed publications, are openly available to the public. These efforts are intended to spur further developments in unknown chemical identification and management towards protecting the environment and human health

    Proceedings of the Seventh Italian Conference on Computational Linguistics CLiC-it 2020

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    On behalf of the Program Committee, a very warm welcome to the Seventh Italian Conference on Computational Linguistics (CLiC-it 2020). This edition of the conference is held in Bologna and organised by the University of Bologna. The CLiC-it conference series is an initiative of the Italian Association for Computational Linguistics (AILC) which, after six years of activity, has clearly established itself as the premier national forum for research and development in the fields of Computational Linguistics and Natural Language Processing, where leading researchers and practitioners from academia and industry meet to share their research results, experiences, and challenges

    Newman v. Google

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    3rd amended complain

    Social media narratives in non-communicable disease: their dynamics and value for patients, communities and health researchers

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    Background: Usage of social media is now widespread and growing, as is the number of people living with Non-Communicable Diseases (NCDs) such as diabetes and cancer. This thesis examines how social media are being used to share or discuss NCDs and the benefits, challenges and implications of these trends as a manifestation of digital public health. Aim and research questions: The aim of this research is to address the gap in empirical, evidence-based research into the secondary use of data from social media to understand patient health issues and inform public health research into NCDs. To this end, seven research questions, each linked to a sub-project, were defined and tested during the course of the six-year programme: 1.What is the status of the existing multi-disciplinary research literature based on analysis of data posted on social media for public health research, and where are the gaps in this research? 2.Can existing systematic review methods be re-purposed and applied to analyse data posted on social media? 3.How are research sponsors and researchers addressing the ethical challenges of analysing data posted on social media? 4.To what extent are diabetes-related posts on Twitter relevant to the clinical condition and what topics and intentions are represented in these posts? 5.In what ways do people affected by Type 1 diabetes use different social media (e.g. for social interaction, support-seeking, information-sharing) and what are the implications for researchers wishing to use these data sources in their studies? 6.Are these differences in platform usage and associated data types also seen in people affected by lung cancer? 7.Can characteristic illness trajectories be seen in a cancer patient’s digital narrative and what insights can be gained to inform palliative care services? Methods: A range of different qualitative and quantitative methods and frameworks were used to address each of the research questions listed. Arksey and O’Malley’s five-stage scoping review framework and the PRISMA guidelines are applied to the systematic scoping review of existing literature. The PRISMA guidelines and checklist are re-purposed and applied to the manual extraction and analysis of social media posts. Bjerglund-Andersen and Söderqvist’s typology of social media uses in research and Conway’s taxonomy of ethical considerations are used to classify the ethics guidelines available to researchers. The findings of these were used to inform the research design of the four empirical studies. The methods applied in the conduct of the empirical studies include a content and narrative analysis of cross-sectional and longitudinal data sourced from Twitter, Facebook, the Type 1 diabetes discussion forum on Diabetes.co.uk and the lung cancer discussion forum on Macmillan.org.uk, as well as the application of Bales’ Interaction Process Analysis and Emanuel and Emanuel’s framework for a good death. Results : Of the 49 systematic, quasi-systematic and scoping reviews identified, 24 relate to the secondary use of data from social media, with eight of these focused on infectious disease surveillance and only two on NCDs. Existing reviews tend to be fragmented, narrow in scope and siloed in different academic communities, with limited consideration of the different types of data, analytical methods and ethical issues involved, therefore creating a need for further reviews to synthesise the emerging evidence-base. The rapid increase in the volume of published research is evident, from the results of RQ1, with 87% of the eligible studies published between 2013-2017. Of the 105 eligible empirical studies that focused on NCDs, cancer (54%) and diabetes (20%) dominate the literature. Data is sourced from Twitter (26%), Facebook (14%) and blogs (10%), conducted, published and funded by the medical community. Since 2012, automated methods have increasingly been applied to extract and analyse large volumes of data. Those that use manual methods for extraction did not apply a consistent approach to doing so; the PRISMA guidelines and checklist were therefore re-purposed and applied to analyse data extracted from social media in response to RQ2. The deficit of ethical guidance available to inform research that involves social media data was also identified as a result of RQ3 and the guidelines provided by the ESRC, BPS, AoIR and NIHR were prioritised for the purposes of this research project. Results from the four empirical studies (RQ4-7) reveal that different forms of social interaction and support are represented in the variety of social media platforms available and that this is influenced by the type and nature of the condition with which people are affected, as well as the affordances offered by such platforms. In the pilot study associated with RQ4, Twitter was identified as a ‘noisy’ source of data about diabetes, with only 66% of the sample being relevant to the clinical condition. Twelve per cent of the eligible sample was associated with Type 2 diabetes, compared to 6% for Type 1, and most were information-giving in nature (49%) and correlated with the diagnosis, treatment and management of the condition (44%). A comparison of Twitter to the Type 1 Diabetes community on Facebook and the discussion forum on Diabetes.co.uk for RQ5 indicated that all three social media platforms were used to disseminate information about the condition. However, the Type 1 Diabetes Group on Facebook and the Type 1 discussion forum on Diabetes.co.uk were also used for social interaction and peer support, hence defying the generalisations made in public health studies, where social media platforms were often considered equal or synonymous. The results from the third empirical study into lung cancer (RQ6) support this, indicating that, by virtue of their digital architecture, user base and self-moderating communities, the Lung Cancer Support Group on Facebook and the lung cancer discussion forum on Macmillan.org.uk are more successful in their utility for social interaction and emotional and informational support. Meanwhile, the sample derived from Twitter hashtags showed greater companionship support. The final empirical study in this PhD research project is associated with RQ7 and used longitudinal data posted by a terminally ill patient on Twitter. This revealed that patient activity on social media mirrors the different phases of the end-of-life illness trajectory described in the literature and that it is comparable to or compliments insights garnered using more traditional qualitative research techniques. It also shows the value of such innovative methods for understanding how terminal disease is experienced by and affects individuals, how they cope, how support is sought and obtained and how patients feel about the ability of palliative care services to meet their needs at different stages. Conclusions: The analysis of health data posted on social media continues to be an expanding and evolving field of multi-disciplinary research. The results of the studies included in this thesis reveal the emergence of new methods and ethical considerations to inform research design as well as ethics policy. The re-purposed PRISMA guidelines and checklist were presented at the 2014 Medicine 2.0 Summit and World Congress whilst the review of ethical guidelines was published in the Research Ethics journal. The four empirical studies that extracted and analysed data from social media provide novel insight into the social narratives of those impacted by diabetes and cancer and can be used to inform future research and practice. The results of these studies have, to date, been presented at four international conferences and published in npj Digital Medicine and BMC Palliative Care. Although this thesis and associated publications contribute to an emerging body of knowledge, further research is warranted into the manual versus automated techniques that can be applied and the differences in social interaction and support needed by people affected by different NCDs
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