Experiences of living with long COVID and of accessing healthcare services: a qualitative systematic review.

OBJECTIVE: To explore the experiences of people living with long COVID and how they perceive the healthcare services available to them. DESIGN: Qualitative systematic review. DATA SOURCES: Electronic literature searches of websites, bibliographic databases and discussion forums, including PubMed LitCovid, Proquest COVID, EPPI Centre living systematic map of evidence, medRxiv, bioRxiv, Medline, Psychinfo and Web of Science Core Collection were conducted to identify qualitative literature published in English up to 13 January 2021. INCLUSION CRITERIA: Papers reporting qualitative or mixed-methods studies that focused on the experiences of long COVID and/or perceptions of accessing healthcare by people with long COVID. Title/abstract and full-text screening were conducted by two reviewers independently, with conflicts resolved by discussion or a third reviewer. QUALITY APPRAISAL: Two reviewers independently appraised included studies using the qualitative CASP (Critical Appraisal Skills Programme) checklist. Conflicts were resolved by discussion or a third reviewer. DATA EXTRACTION AND SYNTHESIS: Thematic synthesis, involving line-by-line reading, generation of concepts, descriptive and analytical themes, was conducted by the review team with regular discussion. RESULTS: Five studies published in 2020 met the inclusion criteria, two international surveys and three qualitative studies from the UK. Sample sizes varied from 24 (interview study) to 3762 (survey). Participants were predominantly young white females recruited from social media or online support groups. Three analytical themes were generated: (1) symptoms and self-directed management of long COVID; (2) emotional aspects of living with long COVID and (3) healthcare experiences associated with long COVID. CONCLUSIONS: People experience long COVID as a heterogeneous condition, with a variety of physical and emotional consequences. It appears that greater knowledge of long COVID is required by a number of stakeholders and that the design of emerging long COVID services or adaptation of existing services for long COVID patients should take account of patients' experiences in their design.

A scoping review of patient and public perspectives on cell and gene therapies.

Aim: The development and introduction of cell and gene therapies presents complex social and economic issues. Fully addressing these challenges requires engagement with patients and the public. Materials & methods: A systematically conducted scoping review was undertaken to gauge current patient and public knowledge and perspectives, and as such inform requirements for future research, education and engagement activities. Results: A heterogeneous collection of 35 studies were identified. Levels of knowledge among patients and the public were extremely variable. Studies indicated general acceptance of therapies. Conclusion: The review identified the need for tailored educational activities, and in particular the importance of addressing misconceptions. There is also a need for robust qualitative research considering perspectives on current and forthcoming licensed therapies.

Scottish Health Technologies Group: enhancing patient engagement.

OBJECTIVES: The Scottish Health Technologies Group (SHTG) provides evidence support and advice to the National Health Service in Scotland on the use of new and existing health technologies, which, although not medicines, are likely to have significant implications for people's care. The purpose of this paper is to highlight the developments that have taken place in the SHTG's patient involvement processes in the years 2017 to 2019, focusing primarily on specific engagement with patient organizations and considering how the new approaches have been received by stakeholders. METHODS: Feedback from patient organizations that participated in the SHTG submission process, alongside SHTG committee members' views on patient organizations contributions, was gathered primarily via online questionnaires. The number of times that patient organizations were invited and accepted the opportunity to peer-review SHTG advice statements prior to and after the employment of a Public Involvement Advisor (PIA) was analyzed. RESULTS: Completed questionnaires (n = 4) from three case study examples showed high patient organization satisfaction with their experience of the SHTG process. The feedback from SHTG committee members that was gathered indicated that patient organization participation was generally well received. The number of peer reviews from patient organizations for SHTG advice statements in 2018-2019 doubled to 86 percent of the total advice statements (n = 22), compared with 43 percent (n = 14) in 2016-2017. CONCLUSIONS: Significant progress has been made toward improving the SHTG's patient involvement processes. A dedicated PIA post within the SHTG has allowed for a more tailored support to patient organizations and has encouraged their increased participation in SHTG processes.

Patient and public perspectives on cell and gene therapies: a systematic review.

Cell and gene therapies offer opportunities for treating disease with potential to restore function, and cure disease. However, they are not without risk and pose complex logistical, economic, ethical and social challenges for health systems. Here we report our systematic review of the current evidence on patient and public knowledge and perspectives of cell and gene therapies, to inform future research, education and awareness raising activities. We screened 10,735 titles and abstracts, and evaluated the full texts of 151 publications. The final selection was 35 publications. Four themes were generated from the narrative synthesis of the study findings namely: (1) Knowledge and understanding of cell and gene therapies, (2) Acceptance of cell and gene therapies (3) Understanding of risk and benefits of therapy, and (4) Information needs and current sources of information. As potential funders or future recipients, it is important that the public and patients are aware of these therapies, understand the issues involved, and can contribute to the debate. This review highlights the need for appropriate patient and public education on the various aspects of cell and gene therapies. High quality studies exploring patient and public opinions and experiences of cell and gene therapy are required. Patient and public perceptions of these therapies, alongside evidence of clinical and cost-effectiveness, will be central to their uptake and use.

Optimization of an MMPB Lemieux Oxidation method for the quantitative analysis of microcystins in fish tissue by LC-QTOF MS.

Microcystins are toxic heptapeptides produced by cyanobacteria in marine and freshwater environments. In biological samples such as fish, microcystins can be found in the free form or covalently bound to protein phosphatases type I and II. Total microcystins in fish have been quantified in the past using the Lemieux Oxidation approach, where all toxins are oxidated to a common fragment (2-methyl-3-methoxy-4-phenylbutyric acid, MMPB) regardless of their initial amino acid configuration or form (free or protein bound). These studies have been carried out using different experimental conditions and employed different quantification strategies. The present study has further investigated the oxidation step using a systematic approach, to identify the most important factors leading to a higher, more robust MMPB generation yield from fish tissue in order to reduce the method detection limit. Field samples were quantified using an in-situ generated MMPB matrix matched calibration curve by isotope dilution with d3-MMPB via liquid chromatography coupled to time-of-flight mass spectrometry (LC-QTOF MS). This approach improves method's accuracy by taking into account of potential matrix effects that could affect the derivatization, sample prepation and instrumental analysis steps. The validated method showed 16.7% precision (RSD) and +6.7% accuracy (bias), with calculated method detection limits of 7.28 ng g-1 Performance of the method was assessed with the analysis of laboratory exposed Rainbow Trout (Oncorhynchus mykiss) to cyanobacteria as a positive control, where no microcystins were detected in the pre-exposure fish liver and fillet, low levels in the exposed fillet (65.0 ng g-1) and higher levels in the exposed liver (696 ng g-1). Finally, the method was employed for the analysis of 26 fillets (muscle) and livers of Walleye (Sander vitreus) and Yellow Perch (Perca flavescens) from Lake Erie, showing very low concentrations of microcystins in the fillet and higher concentrations in liver, up to 3720 ng g-1.

Dioxins in Great Lakes fish: Past, present and implications for future monitoring.

Dioxins/furans are considered among the most toxic anthropogenic chemicals, and are ubiquitous in the environment including in the North American Great Lakes, which contain one fifth of the world's surface freshwater. Our exposure to dioxins/furans is mainly through contaminated diet. Elevated levels of dioxins/furans in Great Lakes fish have resulted in issuance of fish consumption advisories. Here we examine spatial/temporal trends of dioxins/furans in the edible portion (fillet) of fish from the Canadian waters of the Great Lakes using the data collected by the Province of Ontario, Canada. Our analyses show that the Toxic Equivalent (TEQ) dioxin/furan concentrations declined between 1989 and 2013 in Lake Trout from Lakes Ontario, Huron and Superior by 91%, 78% and 73%, respectively, but increased in Lake Whitefish from Lake Erie by 138%. An expanded dataset created by combining our data with historical Lake Ontario Lake Trout measurements from the literature showed a greater decline of >96% (from 64 to 2.3 pg/g) between 1977 and 2013. Measurements collected for 30 types of fish show overall low levels but local/regional concerns at some locations in Lakes Huron, Erie and Ontario. Dioxins/furans are globally present in foodstuff and "zero concentration" target is considered impractical. Based on the observations for the Great Lakes in the context of risk to human health from eating fish, it is concluded that comprehensive monitoring of dioxins/furans can be replaced with targeted locations and/or indicator species, and the saved resources can be more efficiently utilized for monitoring of other priority or emerging contaminants.

Levels, patterns, trends and significance of polychlorinated naphthalenes (PCNs) in Great Lakes fish.

Polychlorinated naphthalenes (PCNs) were introduced to market about a century ago and their production is thought to have ceased by the early 1980s. However, relatively limited knowledge exists on their abundance in the edible portion of a variety of Great Lakes fish to aid in understanding their potential risk to human consumers. We studied levels, patterns, trends and significance of PCNs in a total 470 fillet samples of 18 fish species collected from the Canadian waters of the Great Lakes between 2006 and 2013. A limited comparison of fillet and wholebody concentrations in Carp and Bullhead was also conducted. The ∑PCN ranged from 0.006-6.7ng/g wet weight (ww) and 0.15-190ng/g lipid weight (lw) with the dominant congeners being PCN-52/60 (34%), -42 (21%) and -66/67 (15%). The concentrations spatially varied in the order of the Detroit River>Lakes Erie>Ontario>Huron>Superior. PCN-66/67 was the dominating congener contributing on average 76-80% of toxic equivalent concentration (TEQPCN). Contribution of TEQPCN to TEQTotal (TEQDioxins+Furans+dioxin-likePCBs+PCNs) was mostly <15%, especially at higher TEQTotal, and PCB-126 remains the major congener contributing to TEQTotal. The congener pattern suggests that impurities in PCB formulations and thereby historical PCB contamination, instead of unintentional releases from industrial thermal processes, could be an important source of PCNs in Great Lakes fish. A limited temporal change analysis indicated declines in the levels of PCN-66/67 between 2006 and 2012, complemented by previously reported decrease in PCNs in Lake Ontario Lake Trout between 1979 and 2004. The whole body concentrations were 1.4-3.2 fold higher than the corresponding fillets of Carp and Bullhead. Overall, the study results suggest that only targeted monitoring of PCNs in Great Lakes fish, especially at the Detroit River, Lake Erie and Lake Ontario, is necessary to assess continued future improvements of this group of contaminants of concern.

EXPERIENCES IN ADAPTING EUROPEAN NETWORK FOR HEALTH TECHNOLOGY ASSESSMENT RAPID REVIEWS TO INFORM LOCAL DECISION MAKING.

OBJECTIVES: The Scottish Health Technologies Group (SHTG) produces rapid reviews on nonmedicine technologies to inform advice for decision making in the National Health Service in Scotland (NHSScotland). This study describes our experiences and lessons learned in adapting for NHSScotland two rapid Relative Effectiveness Assessments (REAs) produced as part of the European Network for Health Technology Assessment (EUnetHTA) project to test collaborative preparation and then local adaptation. METHODS: The REAs were examined for their relevance to NHSScotland and the feasibility of their adaptation evaluated using a screening toolkit. Some supplementary literature searches were conducted and additional background information on epidemiology and the specific technologies was sought. To inform decision making within Scotland, it was also necessary to identify and review cost-effective analyses. RESULTS: Robust evidence reviews were delivered for NHSScotland. Time saved was less than anticipated, partly due to the need to add in health economic information, and partly because of attempts to supplement and update the EUnetHTA material. The preparation of an accompanying advice statement for NHSScotland enabled the inclusion of local contextual information. CONCLUSIONS: Collaborative production and adaptation of HTAs is feasible and would be aided by the inclusion of cost-effectiveness analyses in the original work. Agencies should develop clear processes for adapting such reviews for their context with the focus on selecting appropriate topics for adaptation, avoiding unnecessary supplementation of the original work, and ensuring local ownership of final advice.

A high throughput targeted and non-targeted method for the analysis of microcystins and anatoxin-A using on-line solid phase extraction coupled to liquid chromatography-quadrupole time-of-flight high resolution mass spectrometry.

Microcystins are cyclic heptapeptide hepatotoxins produced by cyanobacteria in freshwater. Sample preparation for the analysis of these cyanotoxins in water from algal blooms can take up to several days due to the matrix complexity and the low detection limits required to comply with current legislation. Moreover, there is a large number of unknown microcystins that could potentially exist in the environment resulting from different amino acid substitutions into the microcystin skeletal structure. To tackle these problems, the present study involved the development of a high throughput method based on on-line solid phase extraction coupled to liquid chromatography that could provide quantitative results for 12 microcystin variants (LR, YR, RR, HtyR, HilR, WR, LW, LA, LF, LY, Dha7-LR, and Dha7-RR) and anatoxin-A in less than 3 h with detection limits between 0.004 and 0.01 µg L-1 and expanded uncertainty between 4 and 14%. Data-dependent acquisition was employed for the non-targeted analysis of these cyanotoxins. Filtering the data based on structure diagnostic fragments, two unknown microcystin variants not previously reported in the literature were detected. The structures Leu1-microcystin-Met(O)R and Leu1-microcystin-LY were fully characterized by accurate mass measurement, collision-induced dissociation, and fragmentation prediction software.

Fetal development of subcutaneous white adipose tissue is dependent on Zfp423.

OBJECTIVE: Zfp423 is a multi zinc-finger transcription factor expressed in preadipocytes and mature adipocytes in vivo. Our recent work has revealed a critical role for Zfp423 in maintaining the fate of white adipocytes in adult mice through suppression of the beige cell thermogenic gene program; loss of Zfp423 in mature adipocytes of adult mice results in a white-to-beige phenotypic switch. However, the exact requirements of Zfp423 in the fetal stages of early adipose development in vivo have not been clarified. METHOD: Here, we utilize two models that confer adipose-specific Zfp423 inactivation during fetal adipose development (Adiponectin-Cre; Zfp423loxP/loxP and Adiponectin-rtTA; TRE-Cre; Zfp423loxP/loxP). We assess the impact of fetal adipose Zfp423 deletion on the initial formation of adipose tissue and evaluate the metabolic consequences of challenging these animals with high-fat diet feeding. RESULTS: Deletion of Zfp423 during fetal adipose development results in a different phenotype than is observed when deleting Zfp423 in adipocytes of adult mice. Inactivation of Zfp423 during fetal adipose development results in arrested differentiation, specifically of inguinal white adipocytes, rather than a white-to-beige phenotypic switch that occurs when Zfp423 is inactivated in adult mice. This is likely explained by the observation that adiponectin driven Cre expression is active at an earlier stage of the adipocyte life cycle during fetal subcutaneous adipose development than in adult mice. Upon high-fat diet feeding, obese adipose Zfp423-deficient animals undergo a pathological adipose tissue expansion, associated with ectopic lipid deposition and systemic insulin resistance. CONCLUSIONS: Our results reveal that Zfp423 is essential for the terminal differentiation of subcutaneous white adipocytes during fetal adipose tissue development. Moreover, our data highlight the striking adverse effects of pathological subcutaneous adipose tissue remodeling on visceral adipose function and systemic nutrient homeostasis in obesity. Importantly, these data reveal the distinct phenotypes that can occur when adiponectin driven transgenes are activated in fetal vs. adult adipose tissue.

Polybrominated diphenyl ethers (PBDEs) in Great Lakes fish: Levels, patterns, trends and implications for human exposure.

Levels of polybrominated diphenyl ethers (PBDEs) were measured in edible portions of Great Lakes fish, with the goal of examining patterns/trends and evaluating implications for human exposure. A total of 470 fillets of 18 fish species collected from various parts of the Canadian waters of the Great Lakes between 2006 and 2013 were analyzed for 17 (expanded to 33 in 2009) PBDEs. For a limited number of species, fillet to whole body and fillet to eggs PBDEs were compared to examine pattern and concentration among tissue types. Levels and patterns of PBDEs varied dramatically within and among the 18 fish species. Bottom dwelling Common Carp (and White Sucker) exhibited the highest ∑PBDE levels (27-71ng/g). Lake Trout and Lake Whitefish from Lake Superior had higher levels than those from the other Great Lakes; otherwise the spatial trend was Lake Ontario≫Erie~Huron~Superior. The measured levels would result in restriction on consumption of only Common Carp from the Toronto waterfront area, which is in proximity to the most urbanised region on the Canadian side of the basin. Deca-BDE was the major congener in panfish, while BDE-47 was the major congener in top predators and its contribution to ∑PBDE increased with the contamination. Although ∑PBDE was related to fish length and lipid content when all measurements were pooled, the relationships were variable for individual sampling events (species/location/year). Whole body ∑PBDE for bottom dweller Brown Bullhead and Common Carp were 2.6-4.9 times greater and egg ∑PBDE for four fatty Salmon/Trout species were same to 6.5 times greater than the corresponding fillet concentrations. Levels of major lower brominated PBDEs appear to have declined in fish fillets by 46-74% between 2006/07 and 2012. Although PBDE in existing consumer items will remain in-use for a while, it will likely not result in appreciable accumulation of PBDEs in fish. Based on an overall assessment, regular monitoring of PBDEs in Great Lake fish can be replaced with targeted surveillance and focus can be shifted to other in-use flame retardants.

Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program.

The transcriptional regulators Ebf2 and Prdm16 establish and maintain the brown and/or beige fat cell identity. However, the mechanisms operating in white adipocytes to suppress the thermogenic gene program and maintain an energy-storing phenotype are less understood. Here, we report that the transcriptional regulator Zfp423 is critical for maintaining white adipocyte identity through suppression of the thermogenic gene program. Zfp423 expression is enriched in white versus brown adipocytes and suppressed upon cold exposure. Doxycycline-inducible inactivation of Zfp423 in mature adipocytes, combined with ß-adrenergic stimulation, triggers a conversion of differentiated adiponectin-expressing inguinal and gonadal adipocytes into beige-like adipocytes; this reprogramming event is sufficient to prevent and reverse diet-induced obesity and insulin resistance. Mechanistically, Zfp423 acts in adipocytes to inhibit the activity of Ebf2 and suppress Prdm16 activation. These data identify Zfp423 as a molecular brake on adipocyte thermogenesis and suggest a therapeutic strategy to unlock the thermogenic potential of white adipocytes in obesity.

The Healthcare Improvement Scotland evidence note rapid review process: providing timely, reliable evidence to inform imperative decisions on healthcare.

AIM: Rapid review has become widely adopted by health technology assessment agencies in response to demand for evidence-based information to support imperative decisions. Concern about the credibility of rapid reviews and the reliability of their findings has prompted a call for wider publication of their methods. In publishing this overview of the accredited rapid review process developed by Healthcare Improvement Scotland, we aim to raise awareness of our methods and advance the discourse on best practice. METHODS: Healthcare Improvement Scotland produces rapid reviews called evidence notes using a process that has achieved external accreditation through the National Institute for Health and Care Excellence. Key components include a structured approach to topic selection, initial scoping, considered stakeholder involvement, streamlined systematic review, internal quality assurance, external peer review and updating. RESULTS: The process was introduced in 2010 and continues to be refined over time in response to user feedback and operational experience. Decision-makers value the responsiveness of the process and perceive it as being a credible source of unbiased evidence-based information supporting advice for NHSScotland. CONCLUSION: Many agencies undertaking rapid reviews are striving to balance efficiency with methodological rigour. We agree that there is a need for methodological guidance and that it should be informed by better understanding of current approaches and the consequences of different approaches to streamlining systematic review methods. Greater transparency in the reporting of rapid review methods is essential to enable that to happen.

A modified QuEChERS approach for the screening of dioxins and furans in sediments.

A rapid extraction and cleanup method for the screening of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in sediments is described which combines a modified QuEChERS extraction with carbon reversed-phase solid phase extraction cleanup. This approach is compared to the classical Soxhlet extraction and multi-column cleanup method in terms of toxic equivalence quotients (TEQs), precision, instrumental chromatography, method detection limits (MDLs), recovery of (13)C-labelled quantitation standard, sample preparation time, workload capacity, and sustainability factors. TEQs of 32 sediment samples were found to be well correlated and differed by 16 ± 10 % between the two methods. Certified and standard reference sediments differed by 4.1 and 6.7 %, respectively. Precision and instrumental chromatography were comparable. While the modified QuEChERS method had higher MDLs and lower recoveries, in terms of preparation time and workload capacity, the modified QuEChERS approach can prepare approximately 30 samples per day as compared to 10-20 samples in 3 to 4 days for the classic method. The modified QuEChERS method was also found to be safer and greener. The appreciable improvement in capacity makes the modified QuEChERS approach a suitable alternative to the classical method for applications where turnaround time and the number of samples that can be analyzed are more important than minimal detection limits. Graphical Abstract Created using Microsoft Paint for Windows 7 Professional A bar graph with the structures of dioxins and furans on the x axis shows agreement between two sets of data. A legend labels the first set of data as Soxhlet. The Soxhlet set is illustrated as four days crossed off of a calendar page, a Soxhlet extractor, and several packed chromatography columns. The legend identifies the second set of data as QuEChERS. The QuEChERS set is represented by a clock face marked with twenty four hours, two centrifuge tubes containing the sediment and reagents before and after salting out, and a carbon column attached to a reservoir.

INFLUENCE OF HEALTH TECHNOLOGY ASSESSMENT AND ITS MEASUREMENT.

OBJECTIVES: The aim of this study was to obtain information on methods used to measure health technology assessment (HTA) influence, decisions that were influenced, and outcomes linked to HTA. METHODS: Electronic databases were used to locate studies in which HTA influence had been demonstrated. Inclusion criteria were studies that reliably reported consideration by decision makers of HTA findings; comparative studies of technology use before and after HTA; and details of changes in policy, health outcomes, or research that could be credibly linked to an HTA. RESULTS: Fifty-one studies were selected for review. Settings were national (24), regional (12), both national and regional (3) hospitals (9), and multinational (3). The most common approach to appraisal of influence was review of policy or administrative decisions following HTA recommendations (51 percent). Eighteen studies (35 percent) reported interview or survey findings, thirteen (26 percent) reviewed administrative data, and six considered the influence of primary studies. Of 142 decisions informed by HTA, the most common types were on routine clinical practice (67 percent of studies), coverage (63 percent), and program operation (37 percent). The most frequent indications of HTA influence were on decisions related to resource allocation (59 percent), change in practice pattern (31 percent), and incorporation of HTA details in reference material (18 percent). Few publications assessed the contribution of HTA to changing patient outcomes. CONCLUSIONS: The literature on HTA influence remains limited, with little on longer term effects on practice and outcomes. The reviewed publications indicated how HTA is being used in different settings and approaches to measuring its influence that might be more widely applied, such as surveys and monitoring administrative data.

Pdgfrß+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice.

The expansion of white adipose tissue (WAT) in obesity involves de novo differentiation of new adipocytes; however, the cellular origin of these cells remains unclear. Here, we utilize Zfp423(GFP) reporter mice to characterize adipose mural (Pdgfrß(+)) cells with varying levels of the preadipocyte commitment factor Zfp423. We find that adipose tissue contains distinct mural populations, with levels of Zfp423 distinguishing adipogenic from inflammatory-like mural cells. Using our "MuralChaser" lineage tracking system, we uncover adipose perivascular cells as developmental precursors of adipocytes formed in obesity, with adipogenesis and precursor abundance regulated in a depot-dependent manner. Interestingly, Pdgfrß(+) cells do not significantly contribute to the initial cold-induced recruitment of beige adipocytes in WAT; it is only after prolonged cold exposure that these cells differentiate into beige adipocytes. These results provide genetic evidence for a mural cell origin of white adipocytes in obesity and suggest that beige adipogenesis may originate from multiple sources.

Identification and occurrence of analogues of dechlorane 604 in Lake Ontario sediment and their accumulation in fish.

The dechlorane family of flame retardants, which includes Mirex (also known as Dechlorane), Dechlorane Plus (DP), and Dechloranes (Dec) 602, 603, and 604, were manufactured at a facility along the Niagara River, upstream of Lake Ontario. Some of these compounds remain in use. In a previous study, we found Mirex and Dec602 to have greater bioaccumulation potentials than Dec604 and DP based on calculated biota-sediment accumulation factors (BSAFs). In this study, analogues of Dec604, containing fewer bromines and mixed substitutions of bromine and chlorine, were identified in Lake Ontario sediment and fish using high and ultrahigh resolution mass spectrometric techniques. The tribromo-Dec604 (Br3Dec604) analogue, known as Dechlorane 604 Component B (Dec604 CB), was present in lake trout and whitefish at concentrations of 10-60 ng/g lipid weight, approximately 50-200 times greater than concentrations measured for Dec604. In addition, BrDec604 and Br2Dec604 analogues, and mixed Br2Cl2Dec604, Br3ClDec604, Br2ClDec604, and BrCl2Dec604 analogues were also present. We have shown that solutions of Dec604 and Dec604 CB exposed to UV-light undergo photodebromination and give rise to the analogues found in sediment and fish. Dec604 CB and other lesser halogenated analogues of Dec604 show greater bioaccumulation potentials than Dec604, Dec602 and DP, based on BSAFs, which highlight the need to consider likely impurities and degradation products in the assessment of persistent, bioaccumulative, and toxic compounds.

Polybrominated diphenyl ethers in sediment and caged mussels (Elliptio complanata) deployed in the Niagara River.

Polybrominated diphenyl ethers (PBDEs) were detected in caged mussels (Elliptio complanata), deployed in the Niagara River for 3weeks in 2003, 2004 and 2006 and in sediment collected from the river and tributaries. The highest concentrations (measured as the sum of 17 BDE congeners) were in mussels deployed within tributaries to the American side of the River (Cayuga Creek: 11.5ngg(-1) wet wt.; Two Mile Creek 9.5ngg(-1); and Gill Creek: 5.8ngg(-1)). In addition to contributions from the atmosphere, each urban tributary has multiple potential sources of PBDEs which include storm sewers, sewage treatment plants and industries located upstream of the sampling sites. Total PBDE concentrations in sediment ranged from 0.25 to 188ngg(-1). In general, mean mussel tissue concentrations were positively correlated with sediment BDE concentrations. Total PBDE concentrations were higher in mussels deployed at most sites in the Tonawanda Channel which is highly industrialised, compared with mussels deployed on the Canadian side of the upper Niagara River where the surrounding area is generally rural. The sum of BDE-47, -99, -100, -153, -154 and -209 contributed between 92% and 96% of the total BDE concentrations in all of the mussel samples. BDE-209 represented between 39% and 100% of the total BDE in sediment samples. BSAFs in mussels ranged from 1 to 18 depending on the sampling station. Ratios of BDE-47/99 and BDE-100/99 and congener patterns in mussels and sediment were suggestive of the penta formulation as the historical source.

A stochastic model for the development of Bateson-Dobzhansky-Muller incompatibilities that incorporates protein interaction networks.

Speciation is characterized by the development of reproductive isolating barriers between diverging groups. Intrinsic post-zygotic barriers of the type envisioned by Bateson, Dobzhansky, and Muller are deleterious epistatic interactions among loci that reduce hybrid fitness, leading to reproductive isolation. The first formal population genetic model of the development of these barriers was published by Orr in 1995, and here we develop a more general model of this process by incorporating finite protein-protein interaction networks, which reduce the probability of deleterious interactions in vivo. Our model shows that the development of deleterious interactions is limited by the density of the protein-protein interaction network. We have confirmed our analytical predictions of the number of possible interactions given the number of allele substitutions by using simulations on the Saccharomyces cerevisiae protein-protein interaction network. These results allow us to define the rate at which deleterious interactions are expected to form, and hence the speciation rate, for any protein-protein interaction network.

Historic trends of dechloranes 602, 603, 604, dechlorane plus and other norbornene derivatives and their bioaccumulation potential in lake ontario.

Temporal trends and seasonal variation of Dechloranes (Dec) 602, 603, 604, and Chlordene Plus (CP) in Niagara River suspended sediment, a Lake Ontario sediment core, and Lake Ontario lake trout were investigated, with Mirex and Dechlorane Plus (DP) included for comparison. Temporal concentration trends were generally consistent in each of the media for all compounds with the lowest concentrations observed in or after the late 1990s. In Niagara River suspended sediments, all compounds showed seasonal variation over a year with distinct profiles observed. The relative concentration patterns observed were total DP > Mirex > Dec 602 and Dec 604 > Dec 603 > CP in suspended sediments and sediment cores, whereas Mirex was highest in lake trout, followed by Dec 602 and DP. Dec 602 concentrations were 50 to 380 times greater than those of DP in lake trout, indicating Dec 602 has a greater bioaccumulation potential. The estimated biota-sediment accumulation factor (BSAF) for Dec 602 was much greater than for DP in Lake Ontario, and was greater than those calculated for PBDEs, indicating that assessment of some dechlorane compounds is merited if use is ongoing or planned.