This chapter presents a hierarchical Bayesian framework for the system parameter identification of vibrating systems using spatially incomplete and noisy output-only response measurements. The parameters to be identified are treated as random variables, whose distributions are approximated by a finite number of evolving particles. For each realization of the parameters, an output-only Bayesian filter is employed for the unknown input and state estimation, creating thus a bank of filters that are recursively weighted, upon assimilation of the measurement information, and subsequently updated in order to narrow down the range of system parameters and converge to the target values.
Background: Although social support has been consistently associated with recovery from psychological trauma and prevention of posttraumatic stress disorder (PTSD), individual differences in seeking or benefitting from social support in trauma survivors are not well understood. Factors associated with negative internal working models of self and others, emotion dysregulation, and interrupted bonds with an individual's social support groups such as vulnerable attachment and rejection sensitivity could contribute to lower experienced social support and higher levels of PTSD. Objective: The objective of this study was to test a theoretically informed model and investigate how psychosocial variables such as vulnerable attachment styles, rejection sensitivity, and social support are associated with PTSD. Method: Using a cross-sectional survey and path analyses in 141 survivors of trauma (aged 18-69, M = 25.20), the relationship between vulnerable attachment style, rejection sensitivity, and PTSD were investigated. Results: Higher vulnerable attachment, rejection sensitivity, and lower social support were found to be significant predictors of PTSD symptoms (f 2 = 0.75). The relationships from vulnerable attachment to PTSD were mediated by rejection sensitivity and perceived social support. The results supported and extend theoretical models of PTSD that posit a role for predisposing factors in the development and maintenance of the disorder. Conclusion: The findings suggest a potential benefit of identifying vulnerable groups that could benefit from a refinement of existing PTSD interventions by targeting the maladaptive effects of vulnerable attachment and rejection sensitivity, thus allowing the individual to draw effectively on social support networks.
Background: The eating habits of children and adults have been impacted by the COVID-19 pandemic, with evidence of increases in snacking and emotional eating, including eating to relieve boredom. We explored the experiences of families with children aged 4-8 years who had recently participated in a healthy eating pilot trial when the first national lockdown began in England. Methods: Eleven mothers were interviewed in April and May 2020. Interview questions were developed based on the COM-B model of behaviour. Four main themes were constructed using inductive thematic analysis. Results: The first theme related to an initial panic phase, in which having enough food was the primary concern. The second related to ongoing challenges during the lockdown, with sub-themes including difficulties accessing food, managing children's food requests and balancing home and work responsibilities. The perception that energy-dense foods met families' needs during this time led to increased purchasing of (and thus exposure to) energy-dense foods. In the third theme, families described a turning point, with a desire to eat a healthier diet than they had in the early stages of the lockdown. Finally, in the fourth theme, families reported a number of strategies for adapting and encouraging a balanced diet with their children. Conclusions: Our results suggest that even if parents have the capability (e.g. knowledge) and motivation to provide a healthy diet for their family, opportunity challenges (e.g. time, access to resources, environmental stressors) mean this is not always practical. Healthy eating interventions should not assume parents lack motivation and should be sensitive to the context within which parents make feeding decisions.
Although monoclonal antibodies have greatly improved cancer therapy, they can trigger side effects due to on-target, off-tumor toxicity. Over the past decade, strategies have emerged to successfully mask the antigen-binding site of antibodies, such that they are only activated at the relevant site, for example, after proteolytic cleavage. However, the methods for designing an ideal affinity-based mask and what parameters are important are not yet well understood. Here, we undertook mechanistic studies using three masks with different properties and identified four critical factors: binding site and affinity, as well as association and dissociation rate constants, which also played an important role. HDX-MS was used to identify the location of binding sites on the antibody, which were subsequently validated by obtaining a high-resolution crystal structure for one of the mask-antibody complexes. These findings will inform future designs of optimal affinity-based masks for antibodies and other therapeutic proteins.
Background: Social cognitive impairments, specifically in facial emotion processing and mental state attribution, are common in post-traumatic stress disorder. However few studies so far have examined whether social cognitive ability impacts on PTSD recovery. Objective: To examine whether baseline social cognitive abilities are associated with treatment outcomes following trauma-focused therapy for PTSD. Method: This is a cohort study that will relate treatment outcomes post-discharge to baseline measures of social cognition (five tasks: Emotion Odd-One-Out Task (Oddity), Reading the Mind in the Eyes Task (RMET), Social Shapes Test (SST), Spontaneous Theory of Mind Protocol (STOMP), and Reflective Functioning Questionnaire (RFQ-8)) in people starting a course of psychological therapy for PTSD (target N = 60). The primary outcome will be pre- to post-treatment change in PTSD symptom severity (assessed using the PTSD Checklist for DSM-5). Secondary outcomes include functional impairment (assessed using the Work and Social Adjustment Scale), drop-out rate, and analyses differentiating participants with DSM-5 PTSD and ICD-11 PTSD and CPTSD. Regression models will be used to examine associations between baseline social cognitive performance and outcome measures while adjusting for potential confounders. Two pilot studies informed the development of our study protocol. The first involved qualitative analysis of interviews with nine participants with lived experience of mental health problems to inform our research questions and study protocol. The second involved trialling social cognitive tasks on 20 non-clinical participants to refine our test battery. Discussion: This study will address a gap in the literature about whether abilities in social cognition in people living with PTSD are associated with treatment-related recovery. Highlights: Impairments in social cognition are recognised in people with PTSD.Few studies have examined whether social cognitive ability is associated with recovery from PTSD.We present a study protocol, developed after pilot testing, to address this question.
Although it is widely recognized that strong program management is essential to achieving better health outcomes, this priority is not recognized in malaria programmatic practices. Increased management precision offers the opportunity to improve the effectiveness of malaria interventions, overcoming operational barriers to intervention coverage and accelerating the path to elimination. Here we propose a combined approach involving quality improvement, quality management, and participative process improvement, which we refer to as Combined Quality and Process Improvement (CQPI), to improve upon malaria program management. We draw on evidence from other areas of public health, as well as pilot implementation studies in Eswatini, Namibia and Zimbabwe to support the proposal. Summaries of the methodological approaches employed in the pilot studies, overview of activities and an outline of lessons learned from the implementation of CQPI are provided. Our findings suggest that a malaria management strategy that prioritizes quality and participative process improvements at the district-level can strengthen teamwork and communication while enabling the empowerment of subnational staff to solve service delivery challenges. Despite the promise of CQPI, however, policy makers and donors are not aware of its potential. Investments are therefore needed to allow CQPI to come to fruition.
We previously proposed that realist randomised controlled trials could be used to evaluate how, for whom and under what conditions complex interventions can be used to activate mechanisms to improve health. While this idea was accepted by some, it was also met with resistance, particularly from some realist evaluators who believe that trials are inextricably positivist and dependent on constant conjunctions to understand causation, and that realist trials are unfeasible because participants and contexts will be insufficiently diverse to enable the testing of context-mechanism-outcome configurations. In this paper, we reflect on analyses of qualitative and quantitative data from the Initiating Change Locally in Bullying and Aggression through the School Environment (INCLSUIVE) trial, and whether these are useful and aligned with realism. We summarise the concerns expressed by realists and reflect on the philosophical and practical challenges that we encountered and whether or not they are related to the trial’s design. Finally, we reflect on the trial’s weaknesses and highlight areas that future researchers might consider when running realist trials. We conclude that realist randomised controlled trials are philosophically coherent, practically feasible, and can produce nuanced findings.
The sediment microbiome is a demographically diverse and functionally active biosphere. Ensuring that data acquired from sediment is truly representative of the microbiome is critical to achieving robust analyses. Sample storage and the processing and timing of nucleic acid purification after environmental sample extraction may fundamentally affect the detectable microbial community and thereby significantly alter resultant data. Direct sequencing of environmental samples is increasingly commonplace due to the advent of the portable Oxford Nanopore MinION sequencing device. Here we demonstrate that storing sediment subsamples at − 20 °C or storing the cores at 4 °C for 10 weeks prior to analysis, has a significant effect on the sediment microbiome analysed using sedimentary DNA (sedDNA), especially for Alpha -, Beta - and Deltaproteobacteria species. Furthermore, these significant differences are observed regardless of sediment type. We show that the taxa which are predominantly affected by storage are Proteobacteria , and therefore recommend on-site purifications are performed to ensure an accurate representation of these taxa are observed in the microbiome. Comparisons of sedimentary RNA (sedRNA) analyses, revealed substantial differences between samples purified and sequenced immediately on-site, samples that were frozen before transportation, and cores that were stored at 4 °C prior to analysis. Our data therefore suggest that a more accurate representation of the sediment microbiome demography and functionality may be achieved by environmental sequencing as rapidly as possible to minimise confounding effects of storage.
Background Many conservation management interventions have been set up to bring win–win outcomes for both biodiversity conservation and the well-being of the local communities. Nevertheless, the implementation process of marine protected areas (MPAs) can generate unexpected outcomes and fail to reach its objectives in addressing communities’ challenges. Therefore, it is crucial to have a better understanding of how MPAs influence the socioeconomic aspects of the coastal communities. This paper describes the protocol to conduct a systematic review which aims to explore and review the evidence that reflects the outcomes of marine site protection on poverty reduction in terms of economic and material living standards among the coastal communities in Southeast Asia. The review question is “What are the outcomes of marine site protection implementation on poverty in terms of material and economic living standards of coastal communities in Southeast Asia?”. Methods The systematic review uses rigorous search strategies and selection methods based on pre-defined eligibility criteria to identify and examine published journal articles and grey literature that are available on the review topic. Relevant studies and grey literature will be extracted from a recent systematic map of the evidence documenting the effect of marine or coastal nature conservation or natural resource management activities on human well-being in Southeast Asia. We will search online databases including Web of Science Core Collection, Ovid Medline ® , Environmental Complete, Scopus, as well as Google Scholar and sources of grey literature for any additional literature available since the evidence map was created. For this review, the populations of interest are from coastal communities in the Southeast Asia region. Comparators to marine site protection will be no intervention and/or pre-MPA implementation. The economic and material living standards, which are the poverty domains, will be evaluated as outcomes. Once we have identified relevant literature, we will perform a critical appraisal, data extraction, and synthesis appropriate to the type of literature found, to investigate the effect of marine site protection on poverty reduction.
Background Early detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity. Results Here we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett’s Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status. Conclusions Given our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacterium F. nucleatum , a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation.
Despite international efforts to limit worker exposure to coal dust, it continues to impact the health of thousands of miners across Europe. Airborne coal dust has been studied to improve risk models and its control to protect workers. Particle size distribution analyses shows that using spraying systems to suppress airborne dusts can reduce particulate matter concentrations and that coals with higher ash yields produce finer dust. There are marked chemical differences between parent coals and relatively coarse deposited dusts (up to 500 µm, DD 500 ). Enrichments in Ca, K, Ba, Se, Pb, Cr, Mo, Ni and especially As, Sn, Cu, Zn and Sb in the finest respirable dust fractions could originate from: (i) mechanical machinery wear; (ii) variations in coal mineralogy; (iii) coal fly ash used in shotcrete, and carbonates used to reduce the risk of explosions. Unusual enrichments in Ca in mine dusts are attributed to the use of such concrete, and elevated K to raised levels of phyllosilicate mineral matter. Sulphur concentrations are higher in the parent coal than in the DD 500 , probably due to relatively lower levels of organic matter. Mass concentrations of all elements observed in this study remained below occupational exposure limits.
Male colour patterns of the Trinidadian guppy ( Poecilia reticulata ) are typified by extreme variation governed by both natural and sexual selection. Since guppy colour patterns are often inherited faithfully from fathers to sons, it has been hypothesised that many of the colour trait genes must be physically linked to sex determining loci as a ‘supergene’ on the sex chromosome. Here, we phenotype and genotype four guppy ‘Iso-Y lines’, where colour was inherited along the patriline for 40 generations. Using an unbiased phenotyping method, we confirm the breeding design was successful in creating four distinct colour patterns. We find that genetic differentiation among the Iso-Y lines is repeatedly associated with a diverse haplotype on an autosome (LG1), not the sex chromosome (LG12). Moreover, the LG1 haplotype exhibits elevated linkage disequilibrium and evidence of sex-specific diversity in the natural source population. We hypothesise that colour pattern polymorphism is driven by Y-autosome epistasis.
This is an empirical study of teacher experiences with school learners (7–18 years) engaging in cross-curricular environmental science during the COVID-19 pandemic. The study focuses on #FieldworkLive, a programme of live-streamed outdoor science lessons produced by the Field Studies Council and Encounter Edu during the UK lockdown (April – May 2020). The experiences of approximately 377,000 teachers and students from 32 countries were captured using an online survey and direct staff consultation. This delivery method allowed us to reach untapped audiences and to provide learners with a virtual fieldwork experience during the constraints of lockdown. Teachers were highly positive about the technology-enhanced learning which provided them with novel perspectives and approaches for the classroom. We propose a model for the affordances provided by this delivery approach based on the Technological Pedagogical Content Knowledge framework. The Field Studies Council has developed a flexible package of multimedia resources for secondary schools as a route to enriching outdoor experience and learning despite the constraints imposed by the pandemic.
Background: This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. Methods/results: We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisa- tion of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individu- als, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. Conclusions: We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not display- ing the classic features.
Background Antimicrobial resistance (AMR) is predicted to become the leading cause of death by 2050 with antibiotic resistance being an important component. Anthropogenic pollution introduces antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) to the natural environment. Currently, there is limited empirical evidence demonstrating whether humans are exposed to environmental AMR and whether this exposure can result in measurable human health outcomes. In recent years there has been increasing interest in the role of the environment and disparate evidence on transmission of AMR to humans has been generated but there has been no systematic attempt to summarise this. We aim to create two systematic maps that will collate the evidence for (1) the transmission of antibiotic resistance from the natural environment to humans on a global scale and (2) the state of antibiotic resistance in the environment in the United Kingdom. Methods Search strategies were developed for each map. Searches were undertaken in 13 bibliographic databases. Key websites were searched and experts consulted for grey literature. Search results were managed using EndNote X8. Titles and abstracts were screened, followed by the full texts. Articles were double screened at a minimum of 10% at both stages with consistency checking and discussion when disagreements arose. Data extraction occurred in Excel with bespoke forms designed. Data extracted from each selected study included: bibliographic information; study site location; exposure source; exposure route; human health outcome (Map 1); prevalence/percentage/abundance of ARB/antibiotic resistance elements (Map 2) and study design. EviAtlas was used to visualise outputs. Results For Map 1, 40 articles were included, from 11,016 unique articles identified in searches, which investigated transmission of AMR from the environment to humans. Results from Map 1 showed that consumption/ingestion was the most studied transmission route. Exposure (n = 17), infection (n = 16) and colonisation (n = 11) being studied as an outcome a similar number of times, with mortality studied infrequently (n = 2). In addition, E. coli was the most highly studied bacterium (n = 16). For Map 2, we included 62 studies quantifying ARB or resistance elements in the environment in the UK, from 6874 unique articles were identified in the searches. The most highly researched species was mixed communities (n = 32). The most common methodology employed in this research question was phenotypic testing (n = 37). The most commonly reported outcome was the characterisation of ARBs (n = 40), followed by characterisation of ARGs (n = 35). Other genetic elements, such as screening for intI1 (n = 15) (which encodes a Class 1 integron which is used as a proxy for environmental ARGs) and point mutations (n = 1) were less frequently reported. Both maps showed that research was focused towards aquatic environments. Conclusions Both maps can be used by policy makers to show the global (Map 1) and UK (Map 2) research landscapes and provide an overview of the state of AMR in the environment and human health impacts of interacting with the environment. We have also identified (1) clusters of research which may be used to perform meta-analyses and (2) gaps in the evidence base where future primary research should focus.
The internal validity of conclusions about effectiveness or impact in systematic reviews, and of decisions based on them, depends on risk of bias assessments being conducted appropriately. However, a random sample of 50 recently-published articles claiming to be quantitative environmental systematic reviews found 64% did not include any risk of bias assessment, whilst nearly all that did omitted key sources of bias. Other limitations included lack of transparency, conflation of quality constructs, and incomplete application of risk of bias assessments to the data synthesis. This paper addresses deficiencies in risk of bias assessments by highlighting core principles that are required for risk of bias assessments to be fit-for-purpose, and presenting a framework based on these principles to guide review teams on conducting risk of bias assessments appropriately and consistently. The core principles require that risk of bias assessments be Focused, Extensive, Applied and Transparent (FEAT). These principles support risk of bias assessments, appraisal of risk of bias tools, and the development of new tools. The framework follows a Plan-Conduct-Apply-Report approach covering all stages of risk of bias assessment. The scope of this paper is comparative quantitative environmental systematic reviews which address PICO or PECO-type questions including, but not limited to, topic areas such as environmental management, conservation, ecosystem restoration, and analyses of environmental interventions, exposures, impacts and risks.
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