Marine harmful algal blooms (HABs) in the united states: history, current status and future trends

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Anderson, D. M., Fensin, E., Gobler, C. J., Hoeglund, A. E., Hubbard, K. A., Kulis, D. M., Landsberg, J. H., Lefebvre, K. A., Provoost, P., Richlen, M. L., Smith, J. L., Solow, A. R., & Trainer, V. L. Marine harmful algal blooms (HABs) in the united states: history, current status and future trends. Harmful Algae, 102, (2021): 101975, https://doi.org/10.1016/j.hal.2021.101975.Harmful algal blooms (HABs) are diverse phenomena involving multiple. species and classes of algae that occupy a broad range of habitats from lakes to oceans and produce a multiplicity of toxins or bioactive compounds that impact many different resources. Here, a review of the status of this complex array of marine HAB problems in the U.S. is presented, providing historical information and trends as well as future perspectives. The study relies on thirty years (1990–2019) of data in HAEDAT - the IOC-ICES-PICES Harmful Algal Event database, but also includes many other reports. At a qualitative level, the U.S. national HAB problem is far more extensive than was the case decades ago, with more toxic species and toxins to monitor, as well as a larger range of impacted resources and areas affected. Quantitatively, no significant trend is seen for paralytic shellfish toxin (PST) events over the study interval, though there is clear evidence of the expansion of the problem into new regions and the emergence of a species that produces PSTs in Florida – Pyrodinium bahamense. Amnesic shellfish toxin (AST) events have significantly increased in the U.S., with an overall pattern of frequent outbreaks on the West Coast, emerging, recurring outbreaks on the East Coast, and sporadic incidents in the Gulf of Mexico. Despite the long historical record of neurotoxic shellfish toxin (NST) events, no significant trend is observed over the past 30 years. The recent emergence of diarrhetic shellfish toxins (DSTs) in the U.S. began along the Gulf Coast in 2008 and expanded to the West and East Coasts, though no significant trend through time is seen since then. Ciguatoxin (CTX) events caused by Gambierdiscus dinoflagellates have long impacted tropical and subtropical locations in the U.S., but due to a lack of monitoring programs as well as under-reporting of illnesses, data on these events are not available for time series analysis. Geographic expansion of Gambierdiscus into temperate and non-endemic areas (e.g., northern Gulf of Mexico) is apparent, and fostered by ocean warming. HAB-related marine wildlife morbidity and mortality events appear to be increasing, with statistically significant increasing trends observed in marine mammal poisonings caused by ASTs along the coast of California and NSTs in Florida. Since their first occurrence in 1985 in New York, brown tides resulting from high-density blooms of Aureococcus have spread south to Delaware, Maryland, and Virginia, while those caused by Aureoumbra have spread from the Gulf Coast to the east coast of Florida. Blooms of Margalefidinium polykrikoides occurred in four locations in the U.S. from 1921–2001 but have appeared in more than 15  U.S. estuaries since then, with ocean warming implicated as a causative factor. Numerous blooms of toxic cyanobacteria have been documented in all 50  U.S. states and the transport of cyanotoxins from freshwater systems into marine coastal waters is a recently identified and potentially significant threat to public and ecosystem health. Taken together, there is a significant increasing trend in all HAB events in HAEDAT over the 30-year study interval. Part of this observed HAB expansion simply reflects a better realization of the true or historic scale of the problem, long obscured by inadequate monitoring. Other contributing factors include the dispersion of species to new areas, the discovery of new HAB poisoning syndromes or impacts, and the stimulatory effects of human activities like nutrient pollution, aquaculture expansion, and ocean warming, among others. One result of this multifaceted expansion is that many regions of the U.S. now face a daunting diversity of species and toxins, representing a significant and growing challenge to resource managers and public health officials in terms of toxins, regions, and time intervals to monitor, and necessitating new approaches to monitoring and management. Mobilization of funding and resources for research, monitoring and management of HABs requires accurate information on the scale and nature of the national problem. HAEDAT and other databases can be of great value in this regard but efforts are needed to expand and sustain the collection of data regionally and nationally.Support for DMA, MLR, and DMK was provided through the Woods Hole Center for Oceans and Human Health (National Science Foundation grant OCE-1840381 and National Institutes of Health grants NIEHS‐1P01-ES028938–01) and the U.S. National Office for Harmful Algal Blooms with funding from NOAA's National Centers for Coastal Ocean Science (NCCOS) through the Cooperative Institute for the North Atlantic Region (CINAR) (NA14OAR4320158, NA19OAR4320074). Funding for KAL and DMA was provided by the National Oceanic and Atmospheric Administration National Centers for Coastal Ocean Science Competitive Research Program under award NA20NOS4780195 to the Woods Hole Oceanographic Institution and NOAA's Northwest Fisheries Science Center. We also acknowledge support for A.H. from the National Oceanic and Atmospheric Administration [NOAA] Office of Ocean and Coastal Resource Management Award NA19NOS4780183, C.J.G from NOAA-MERHAB (NA19NOS4780186) and (NA16NOS4780189) for VLT Support was also received for JLS, CJG, and VLT from NOAA-NCCOS-ECOHAB under awards NA17NOS4780184 and NA19NOS4780182. This is ECOHAB publication number ECO972

Impact of pre-analytical and analytical variables associated with sample preparation on flow cytometric stainings obtained with EuroFlow panels

Objective interpretation of FC results may still be hampered by limited technical standardization. The EuroFlow consortium conducted a series of experiments to determine the impact of different variables on the relative distribution and the median fluorescence intensity (MFI) of markers stained on different cell populations, from both healthy donors and patients’ samples with distinct hematological malignancies. The use of different anticoagulants; the time interval between sample collection, preparation, and acquisition; pH of washing buffers; and the use of cell surface membrane-only (SM) vs. cell surface plus intracytoplasmic (SM+CY) staining protocols, were evaluated. Our results showed that only monocytes were represented at higher percentages in EDTA- vs. heparin-anticoagulated samples. Application of SM or SM+CY protocols resulted in slight differences in the percentage of neutrophils and debris determined only with particular antibody combinations. In turn, storage of samples for 24 h at RT was associated with greater percentage of debris and cell doublets when the plasma cell disorder panel was used. Furthermore, 24 h storage of stained cells at RT was selectively detrimental for MFI levels of CD19 and CD45 on mature B- and T-cells (but not on leukemic blasts, clonal B- and plasma cells, neutrophils, and NK cells). The obtained results showed that the variables evaluated might need to be tailored for sample and cell type(s) as well as to the specific markers compared; however, defining of well-balanced boundaries for storage time, staining-to-acquisition delay, and pH of washing buffer would be a valid recommendation for most applications and circumstances described herein.This research was funded by the EuroFlow Consortium which received support from the FP6-2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The EuroFlow Consortium is part of the European Scientific Foundation for Hemato-Oncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA); the grant of the Polish National Center for Research and Development (no. STRATEGMED3/304586/5/NCBR/2017 Person ALL); and internal grant of the Medical University of Silesia (no. PCN-1-050/K/0/K); the grant of CIBER-ONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER (no. CB16/12/00400)

Are vaccination programmes delivered by lay health workers cost-effective? A systematic review

<p>Abstract</p> <p>Background</p> <p>A recently updated Cochrane systematic review on the effects of lay or community health workers (LHWs) in primary and community health care concluded that LHW interventions could lead to promising benefits in the promotion of childhood vaccination uptake. However, understanding of the costs and cost-effectiveness of involving LHWs in vaccination programmes remains poor. This paper reviews the costs and cost-effectiveness of vaccination programme interventions involving LHWs.</p> <p>Methods</p> <p>Articles were retrieved if the title, keywords or abstract included terms related to 'lay health workers', 'vaccination' and 'economics'. Reference lists of studies assessed for inclusion were also searched and attempts were made to contact authors of all studies included in the Cochrane review. Studies were included after assessing eligibility of the full-text article. The included studies were then reviewed against a set of background and technical characteristics.</p> <p>Results</p> <p>Of the 2616 records identified, only three studies fully met the inclusion criteria, while an additional 11 were retained as they included some cost data. Methodologically, the studies were strong but did not adequately address affordability and sustainability and were also highly heterogeneous in terms of settings and LHW outcomes, limiting their comparability. There were insufficient data to allow any conclusions to be drawn regarding the cost-effectiveness of LHW interventions to promote vaccination uptake. Studies focused largely on health outcomes and did illustrate to some extent how the institutional characteristics of communities, such as governance and sources of financial support, influence sustainability.</p> <p>Conclusion</p> <p>The included studies suggest that conventional economic evaluations, particularly cost-effectiveness analyses, generally focus too narrowly on health outcomes, especially in the context of vaccination promotion and delivery at the primary health care level by LHWs. Further studies on the costs and cost-effectiveness of vaccination programmes involving LHWs should be conducted, and these studies should adopt a broader and more holistic approach.</p

Identification of miRSNPs associated with the risk of multiple myeloma

Accepted articleMultiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression. MiRSNPs are known to be associated with risk of various types of cancer, but they have never been investigated in MM. We performed an in silico genome-wide search for miRSNPs predicted to alter binding of miRNAs to their target sequences. We selected 12 miRSNPs and tested their association with MM risk. Our study population consisted of 1,832 controls and 2,894 MM cases recruited from seven European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with p<0.05: rs286595 (located in gene MRLP22) and rs14191881 (located in gene TCF19). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3UTR of the POU5F1 gene), rs1419881 (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with MM risk. In conclusion, we sought to identify genetic polymorphisms associated with MM risk starting from genome-wide prediction of miRSNPs. For some mirSNPs, we have shown promising associations with MM risk. What's new? Even though deregulation of miRNA expression has been associated with human cancers little information is available regarding their relation with MM susceptibility. We performed an in silico genome-wide search for miRSNPs and selected the most promising ones for an association study. The SNPs with the strongest associations with MM risk are localized in genes which have never been related with MM.This work was partially funded by: intramural funds of German Cancer Research Center (DKFZ), Grant ref. HUS412A1271 from the “Gerencia Regional de Salud de la Junta de Castilla y Léon”. This work was supported by grants from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688). Catalan Government DURSI grant 2014SGR647 and Instituto de Salud Carlos III, co7funded by FEDER funds –a way to build Europe– grants PI11701439 and PIE13/00022info:eu-repo/semantics/publishedVersio

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries