AbstractDiptera fauna is updated. Numbers of species currently known from Canada, total Barcode Index Numbers (BINs), and estimated numbers of undescribed or unrecorded species are provided for each family. An overview of recent changes in the systematics and Canadian faunistics of major groups is provided as well as some general information on biology and life history. A total of 116 families and 9620 described species of Canadian Diptera are reported, representing more than a 36% increase in species numbers since the last comparable assessment by JF BINs have so far been obtained from flies in Canada. Estimates of additional number of species remaining to be documented in the country range from 5200 to 20,400.The Canadian  This paper is dedicated to the memory of Terry A Wheeler, an exceptional Canadian dipterist and long-time contributor to the Biological Survey of Canada, who passed away in the early stages of this project.Diptera counts almost 160,000 named species , flies have diversified to exploit almost all organic substrates for their development (see Chironomidae (non-biting midges), whose immature stages are primarily aquatic, account for the most named species (798) in a single family  gene . DNA barcoding and the Barcode Index Number (BIN) system  or the Sciaridae (129 vs 2863)  gene  has been) system  usually Muscidae  and Simumuliidae . Howevermuliidae , as wellDipteraManual of Nearctic , especially Volume 3 . While the Oreoleptidae and the Richardiidae represent new records for the country, most of the additional families represent reclassification of taxa formerly combined with other families (see text below and Table Tipulidae and Empididae) or those in which numerous synonymies were uncovered . Especially worth noting are the Sphaeroceridae and Anthomyzidae, with five- and nine-fold increases in species numbers since 1979, respectively. In each of these cases, the impressive increase in species numbers can be attributed to decades-long dedication to biosystematics study of particular families by individuals and institutions .When compared to the data provided in JF Diptera in Canada (mistakenly reported as 7058 in table 42) and estimated that an approximately equivalent number remained to be discovered. The 9620 species reported here represents a 36% increase since 1979. Significant advances have been made over the last four decades but some major gaps remain. While few families are known well enough to claim full coverage in Canada, the bulk of undescribed or unrecorded Canadian Diptera diversity is in the nematocerous families, especially those with diminutive and/or delicate adults such as the Chironomidae, Ceratopogonidae, Cecidomyiidae and Mycetophilidae, all of which are in great need of taxonomic attention (Table JF Diptera (Lower Diptera), previously known as Nematocera, include those species of adult flies with elongate antennae composed of at least four flagellomeres. The group includes 36 extant families worldwide, of which 33 occur in Canada. The concepts and names of many families have changed since JF The nematocerous Diptera tend to be long-legged and, compared to brachyceran Diptera, weaker fliers. Larvae are found in a wide array of habitats and include a large number of aquatic and semiaquatic taxa (see Tipulomorpha and Culicomorpha below), fungal feeders, gall makers, detritus feeders, predators, and even parasites, among others. The biting flies are mostly in the Culicomorpha and include those species that vector important diseases of humans, domestic animals and wildlife.As adults, nematocerous Diptera are clearly paraphyletic in relation to the Brachycera, although the exact sister group of Brachycera within the nematocerous Diptera is not certain , a small family now formally recognized as the sister group to the Tipulidae s. lat. (crane flies) (The major change to this infraorder since JF he World  and BOLDe flies) .Limoniidae (354 species in Canada) and Tipulidae (216), representing an increase of 21% since JF Chionea Dalman (Dicranoptycha Osten Sachen (Symplecta (Symplecta Meigen) (Limoniidae and of Nephrotoma Meigen (Prionocera Loew (Tipula (Eremotipula Alexander)  has not changed much since 1979, but 10 more species are expected in Canada   in the La Meigen , Prionocera Loew , and Tipexander)  in the Tn Arctic , 2000 ann Arctic . There apulidae 26, represpulidae 26, represLimonia Meigen and Metalimnobia Matsumura species), or carnivorous (some Limoniidae and Pediciidae species), and Cylindrotomidae are phytophagous. Tipulapaludosa Meigen and T.oleracea (Linnaeus) are established pests of dairy lands and golf courses , we have chosen not to assign these two families to infraorder.The placement of these two families remains controversial. Previously, they have both been assigned to the infraorder romorpha , Nymphomcomorpha , and one is recorded from Quebec and New Brunswick  and Neodiptera  families  has decreased from the 1979 estimate, due to several synonymies  remain to be documented .The Ptychopteromorpha for two small families of flies, Ptychopteridae and Tanyderidae. Molecular and morphological evidence supporting the transfer of the Tanyderidae to the Psychodomorpha  currently stand as the most species-rich family of Diptera in Canada, and at least 1000 additional species are expected to occur in the country (Table Chaoboridae (11 species in Canada), Thaumaleidae (13) and Dixidae (34) are represented by relatively few species , Simuliidae (164) and Ceratopogonidae (263) are all quite diverse, whereas a single species of Corethrellidae (formerly in Chaoboridae) is known for the country (Table Culicidae (mosquitoes) and Simuliidae (black flies) are both very well known, but while only three additional mosquito species are estimated to be unrecorded, a further 20 species of black flies are expected to eventually be documented in Canada (Table Ceratopogonidae (biting midges) are by far the most poorly known of biting flies. There are close to ten times as many BINs as recorded species for the group and it is thought that less than half of the Canadian fauna is known to date   , or cons s. str. .Axymyiidae are a small family of Holarctic flies with a single eastern species, Axymyiafurcata McAtee, recorded from Canada  but two species from the Pacific Northwest , whereas Bibionidae, Pachyneuridae, and Sciaroidea. Bibionomorpha: Bibionidae, Pachyneuridae (in part), Sciaroidea, and Anisopodidae. More recently molecular analyses have again supported the broad concept sensu Perissommatidae (Perissommatidae and Axymyiidae (Scatopsoidea. Recently Perissommatidae show derived attributes of the Bibionomorpha s. str. Given these conflicting classifications we have chosen to use both narrow (s. str.) and broad (s. lat.) concepts of the group as followed in Bibionomorpha s. str. have been studied by The boundaries of the mmatidae  or excluymyiidae . GrimaldBibionomorpha s. str. due to the absence of a highly modified and multi-chambered accessory gland and different configuration of the ejaculatory apodeme (Anisopodidae and Canthyloscelidae (= Synneuridae) have low diversity in Canada  but the Scatopsidae are represented by 30 species, with 15–20 more expected , Bibionidae (26), Hesperinidae , and the following four families, formerly included in Mycetophilidae by J.F. Ditomyiidae (3), Bolitophilidae (16), Keroplatidae (28) and Diadocidiidae (2) (Table Bibionidae known from Canada has decreased by approximately a third from the 1979 estimate (Table Seven of the ten families of Sciaridae (129 species in Canada) has quadrupled since 1979 (Table Cecidomyiidae (243 species in Canada) have more than doubled since 1979 and those of Mycetophilidae now reach 489 species, thereby representing the highest documented diversity of any family in this infraorder  made up of 3–8 fused flagellomeres. The group is very diverse with 83 families occurring in Canada   , the terde e.g., . Divisiogomorpha , Tabanomnomorpha , Stratioyomorpha  and Asillomorpha . Severalleptidae  and elevomyiidae  and Mythomyiidae  from RhaXylophagidae, although some authors have divided it into smaller family units  and Bolbomyiidae. The classification of Tabanomorpha occur in Canada and these are organized in two superfamilies. In Rhagionoidea, Bolbomyiidae include three known species in Canada and two more are expected , Athericidae (2), and the recently erected monotypic family Oreoleptidae (1) (Tabanidae (horse flies and deer flies) are much better known than most insects in Canada, with keys and illustrations known for all 142 species (Athericidae and Oreoleptidae occur in riffle zones and/or vegetation of cool streams and flowing rivers. Those of Pelecorhynchidae and Tabanidae are predators of invertebrates found mostly in wetland soils.In idae 1) ; Table 1 ; Table  species  as well  species . With thStratiomyomorpha includes three families, of which the Stratiomyidae and the Xylomyidae occur in Canada while the Pantophthalmidae are restricted to the Neotropics. The sister-group relationship of Stratiomyidae and Xylomyidae is strongly supported, especially by larval characters , which could reveal a few undescribed species as well as some synonyms. Only two genera and seven species of Xylomyidae are known from Canada  is now generally considered polyphyletic with the three parasitic families considered to be distantly related  has received a great deal of focus over the past decades , Mydidae (2), Mythicomyiidae (1), Hilarimorphidae (7), and Scenopinidae (10)  has nearly doubled, primarily through the recent publications of Bombyliidae in Canada is outlined in a world catalogue , which is considered to be either the sister group of Cyclorrhapha   and Oreogetonidae), because of the availability of family-group names   and threup names . The Iteagadidae . RecogniOreogetonidae (7 species), Empididae (251), Brachystomatidae (11), Hybotidae (155), and Dolichopodidae s. lat. (508), plus the Iteaphila genus-group (17). Apart from the Dolichopodidae , the remaining groups were lumped into the Empididae in JF Empidoidea is a moderate increase over the 800 species recorded by JF Empididae in Five families of this primarily predaceous group occur in Canada Table : Oreogetididae 25, BrachysOreogetonidae and two subfamilies of Empididae (Clinocerinae and Hemerodromiinae) include species with aquatic larvae. The remaining Empididae are mainly terrestrial and many species are important pollinators . The group is divided into the basal Lower Cyclorrhapha (“Aschiza”) and the monophyletic Schizophora . Schizophora are further divided into the paraphyletic Acalyptratae and the monophyletic Calyptratae.The Aschiza, which traditionally included the cyclorrhaphan families exclusive of Schizophora (or those flies without a ptilinum for exiting the puparium). Only Aschiza concept proposed by Aschiza” are a grade and should be referred to as the Lower Cyclorrhapha  and Opetiidae (non-Nearctic)  , but eveed Table , some reed Table  and moreed Table , routinePhoridae (including Sciadocerinae sensu Ironomyiidae (non-Nearctic) in this superfamily , Diopsidae (2), Strongylophthalmyiidae (2), and Tanypezidae (1). The Canadian fauna of these families appears to be relatively well-known and only a few species have been added in recent decades, but work on Psilidae is still required. Revisions and keys to Nearctic genera and species are available for Diopsidae  rendered them paraphyletic, but most contemporary authors now follow DK Micropezidae.The Micropezidae occur in Canada, one of which is a recently introduced European Micropeza Meigen  and Heterocheilidae (1) as families distinct from Dryomyzidae , Dryomyzidae (8), and Sepsidae (19). For Sciomyzidae (120) and Conopidae (42), species numbers in Canada have increased by approximately 40% since 1979  are parasitoids. Restriction to marine coasts is also common within the group .elopidae ; Conopidonopidae ; Dryomyzomyzidae ; Helcomyomyzidae ; Heterocheilidae ; Sciomyzomyzidae . As wellLauxanioidea, including two families found in Canada, Lauxaniidae and Chamaemyiidae. The current number of reported species in Canada for Lauxaniidae (78) and Chamaemyiidae (35) represent modest increases since 1979, but a few more species of each family are likely to be recorded in the future (Table Lauxanioidea fauna has not been revised since JF Pseudodinia Coquillet (Chamaemyiidae) by Lauxaniidae are suspected to be saprophagous as immatures while those of Chamaemyiidae are parasitoids of aphids and other Sternorrhyncha.The recent molecular analysis of Tephritidoidea” and a paraphyletic “lower Tephritidoidea”, all eight families of which are represented in Canada , Platystomatidae (10), Pyrgotidae (3), and Tephritidae (122). The “lower” families are Piophilidae (31), Pallopteridae (9), Lonchaeidae (99) and Richardiidae (1). Recently, a phylogeny by Tephritidae as paraphyletic, finding Richardiidae to belong to the “higher” group of families and a sister-group relationship to the remaining families. The numbers of known species have been relatively constant since 1979, with the exception of the family Tephritidae, which has tripled  , Aulacigastridae (2), Periscelididae (3), Odiniidae (6), Opomyzidae (11), Anthomyzidae (37) and Clusiidae (22). Numbers of Canadian species for these small families have remained relatively constant since 1979 with the exception of the Anthomyzidae, which increased nine-fold through the revisionary work of Clusiidae, which were fully revised over the past 20 years  were treated in a long series of papers by GCD Griffiths. Apart for the Anthomyzidae and the Clusiidae (see above), little has been published about the remaining families since 1979. Aulacigaster Macquart (the only Aulacigastridae occurring in Canada) and a new invasive Opomyzidae was recorded by The Canadian a Hendel ; Cerodon Rondani , 2012a; myza Mik ; Pseudona Hendel . Many noAgromyzidae being highly pestiferous, but there are also associations with fungi, sap fluxes, frass, and insect galleries in trees. Some taxa are predaceous and a few have larvae that are aquatic to semi-aquatic; Clusiidae to feed on biofilm in decaying wood.Carnoidea , Carnidae (12), and Milichiidae (13). Canacidae were globally catalogued recently , crop pests (some Chloropidae), and parasites in bird’s nests (Carnidae).Of the five da Table , three hrecently  and the ly e.g.,  and withly e.g., . These pEphydroidea , Diastatidae (7), Curtonotidae (1), and Camillidae (2). A few additional species of Diastatidae are expected ; relatively few additions are expected as further collecting is carried out , most recent published works  proposed by Calyptratae has remained mostly unchanged since This large monophyletic subgroup of es e.g., . Wherebyed works  have supHippoboscoidea are presently considered the sister-group to the remaining calyptrates (Glossinidae (tsetse flies) and the Hippoboscidae (louse flies and batflies) with only the latter family found in Canada. JF Nycteribiidae and Streblidae, which are now included as subfamilies of the Hippoboscidae  and the Oestroidea . The most important change relating to the Canadian fauna since JF Fanniidae as distinct from the Muscidae  and numerous synonymies have reduced the number of Canadian muscids to 440. The publication of more than a hundred new anthomyiid species and records . A few generic and type revisions  is the best known member of the group, but immature and adult muscoids exhibit a range of ecological habits so broad that it almost spans the complete spectrum displayed at the order level , but the same five families recognized by JF This large lineage of nearly 15,000 species worldwide  has longTachinidae have a large presence in Canada (Chironomidae as the most speciose family of Diptera in the country based on numbers of described species (Table Sarcophagidae (135 species in Canada) and the Calliphoridae (62) and their species numbers have increased by over 50% since 1979 (Table Oestridae (17 species in Canada) and introduced Rhinophoridae (2) have not undergone any significant changes since JF BINs and known species numbers is generally good in this superfamily except for the Oestridae and, to a lesser extent, the Calliphoridae  but most are saprophagous and associated with decaying animal matter. The Sarcophagidae have the most diverse larval habits of the superfamily; some are kleptoparasites in the nests of solitary bees and wasps, some feed on carrion or dung, and others are associated with living animals as parasitoids (particularly arthropods) or predators. Several parasitic species of Oestridae, Sarcophagidae and Calliphoridae are also known to cause myiasis in humans and other vertebrates (The rm hosts , and somtebrates .


Aquaculture of bivalve shellfish and seaweed represents a global opportunity to simultaneously advance coastal ecosystem recovery and provide substantive benefits to humanity. To identify marine ecoregions with the greatest potential for development of shellfish and seaweed aquaculture to meet this opportunity, we conducted a global spatial analysis using key environmental , socioeconomic , and human health factors . We identify a substantial opportunity for strategic sector development, with the highest opportunity marine ecoregions for shellfish aquaculture centered on Oceania, North America, and portions of Asia, and the highest opportunity for seaweed aquaculture distributed throughout Europe, Asia, Oceania, and North and South America. This study provides insights into specific areas where governments, international development organizations, and investors should prioritize new efforts to drive changes in public policy, capacity-building, and business planning to realize the ecosystem and societal benefits of shellfish and seaweed aquaculture. Globally, coastal ecosystems face numerous complex and interconnected anthropogenic threats, such as nutrient pollution, loss of habitats, and the compounding impacts of climate change . These sWhen managed within a broader ecosystem framework and strategy, aquaculture has the potential to enhance ecosystems and provide increased benefits to humanity , with vaHabitat-forming ecosystem engineers, such as oyster reefs, seagrass beds, and kelp forests, and associated biotic assemblages provide critical ecosystem services, but have suffered extensive losses globally as a result of overharvest, nutrient pollution, and other detrimental human activities ,23,24. OWhile commercial shellfish and seaweed aquaculture can help address a multitude of global environmental challenges and social issues, a variety of societal and human health factors also restrict where safe or sustainable shellfish and seaweed aquaculture can be developed. For example, regions lacking wastewater treatment infrastructure or where heavy metal or persistent organic pollutant concentrations are elevated may lead to production of shellfish or seaweed unfit for human consumption . AdditioIn this study, we conducted a global-scale spatial analysis that incorporated a broad suite of global datasets representing key environmental, socioeconomic, and human health considerations to develop a novel, quantitative global index—the ‘Restorative Aquaculture Opportunity Index’ (RAOI)—to aid in identification of marine ecoregions with substantial opportunity to benefit from ecosystem services provided by development of restorative shellfish and seaweed aquaculture . Specifically, we: (1) convened an expert panel of stakeholders to identify model inputs to the RAOI and weight their relative importance, (2) used a GIS-based modeling approach to integrate spatial data layers representing 16 environmental, socioeconomic, and human health factors to calculate the RAOI under varying scenarios optimized for shellfish and seaweed aquaculture, and (3) assessed sensitivity of the RAOI to the expert weightings and to individual factors. In this study, we identified regions of high opportunity around the world where commercial marine aquaculture may provide environmental and social benefits to drive conservation, public policy, and business planning efforts towards aquaculture systems that enhance ecosystem function, potentially unlocking a pragmatic approach to ecosystem recovery. To illustrate the immediate opportunity available to use restorative aquaculture in this way, we describe the efforts underway to operationalize the results of this study to guide shellfish and seaweed aquaculture development projects around the world.An initial literature review was conducted to understand the broad set of environmental, socioeconomic, and human health dimensions that might define where development of shellfish and seaweed aquaculture could mitigate environmental challenges and ensure societal benefits while accounting for constraints to sustainable development. In particular, we utilized resources such as the recent systematic literature review of ecosystem services associated with aquaculture conducted to determine applicable factors for inclusion within the analysis . ConcurrWe engaged a 13-person stakeholder group to determine factors to include within the RAOI and their associated weightings. The stakeholder group was purposively selected to consist of international expert representatives across the shellfish and seaweed aquaculture sectors, government scientists, private industry, academic and research institutions, non-governmental organizations, and international financial institutions . The stakeholder group determined which factors were to be included in the RAOI  and indeFor each environmental, socioeconomic, and human health factor for which an authoritative global dataset was identified, we followed a standardized protocol to process each dataset within ArcMap 10.5 for integration within the RAOI . Each glsensu [We subsequently defined a suitability function to describe the relationship between each factor and associated opportunity for development of commercial shellfish and seaweed aquaculture . We utilsensu ). LinearIt is important to note that these suitability functions are intended to represent commercial shellfish and seaweed aquaculture suitability relationships at the scale of MEs . When applied at the scale of estuaries for localized spatial planning and siting of specific shellfish and seaweed aquaculture operations, these functions may require modification due to considerations relevant at finer spatial scales .Ej) for shellfish and seaweed aquaculture was calculated as:Ej is the cumulative RAOI score of ecoregion j calculated as the product of the suitability score S of ecoregion j for spatial data layer x and the weight W of layer i summed across all n layers . To determine the sensitivity of the RAOI to individual factors within each scenario, we: (1) sequentially removed the four factors with the highest weight in both the shellfish and seaweed RAOI scenario that incorporated all environmental, socioeconomic, and human health factors—removing each factor one at a time , (2) re-We utilized a suitability analysis framework to develop the RAOI, however, we recognize alternative spatial analysis approaches have merit, particularly for selection of factors and assignment of weightings . Given the intended role of the RAOI to guide on-the-ground seaweed and shellfish aquaculture development projects around the world on behalf of government and NGO institutions, coupled with the importance of including factors beyond the core environmental considerations , it was essential to utilize the expert stakeholder panel approach to guide selection and weighting of the factors considered within the RAOI. The expert stakeholder panel approach allowed for establishment of “buy-in” to the RAOI, ensured inclusion of factors relevant to guiding decisions on aquaculture development, and improved the likelihood of its utilization.We incorporated the best available global datasets from authoritative sources within the spatial analysis. However, in compiling these datasets, data gaps were apparent for some factors for some MEs, particularly within MEs adjacent to low or lower-middle income countries. As the RAOI score in each scenario was calculated based on the cumulative sum of an ME’s score for a given factor multiplied by its associated factor-specific weight, this resulted in a bias towards identified HOMEs  corresponding with those with greater data availability. We addressed this bias in three ways: (1) we conducted the previously described sensitivity analysis to better understand the impact of the stakeholder weightings and individual factors on model output, (2) we produced a global map series that described the amount of data available for each ME that was incorporated within each RAOI scenario, and (3) we generated a map series of complementary output for the six RAOI scenarios where, if there was a data gap for a given factor within a given ME, the weights for factors where data was available were proportionally re-scaled to compute the overall RAOI score.The expert stakeholder group identified 16 factors considered necessary to identify high opportunity marine ecoregions (HOMEs) for shellfish and seaweed aquaculture development that were combined to calculate the ‘Restorative Aquaculture Opportunity Index’ (RAOI) across multiple scenarios  where nutrient inputs are the most elevated represent the highest opportunity locations for development of shellfish and seaweed aquaculture to provide nutrient pollution reduction benefits. High opportunity marine ecoregions (HOMEs)—those receiving the highest RAOI scores—for these benefits include those located throughout Europe and Asia, along the East and Gulf Coasts of North America, and in northern South America  and 9.3% ± 0.4% SE with removal of the aquaculture value (shellfish) factor  distributed throughout Europe, North and South America, Asia, and Oceania were identified as having the highest Restorative Aquaculture Opportunity Index (RAOI) scores within the scenarios that incorporated all environmental, socioeconomic, and human health factors—indicating the substantial opportunity across the globe for shellfish and seaweed aquaculture to provide environmental and socioeconomic benefits  and 4. WOf the top 25 HOMEs for shellfish aquaculture, 9 were located in Oceania , 8 in North America (24%), 5 in Europe (28%), and 3 in Asia 7%; . For seaModerate opportunity MEs were located throughout South America, Asia, and Africa, driven largely by modest environmental and socioeconomic opportunity, and some degree of human health concerns. In some cases, the RAOI scores of MEs with identified elevated environmental opportunity scores  were redIncreasingly, evidence indicates that where aquaculture development is intentionally designed to support beneficial environmental or social outcomes, positive impacts can be returned for both people and the ecosystem . SpatialDevelopment of shellfish and seaweed aquaculture within MEs with high RAOI scores does not guarantee provision of ecosystem services or that ecosystem function will be recovered. While the present study provides valuable insight at the global-scale to guide strategic aquaculture development initiatives at the scale of MEs, ultimately, multiple factors at successive geographic and ecosystem scales will affect the extent of ecosystem delivery of aquaculture and whether farms ultimately improve or degrade ecosystem function. These factors include the functional traits of culture species, abiotic and biotic characteristics of the surrounding environment, farm-design, and farming practices . For exaThe pre-existing extent of ecosystem degradation in a given location can make developing commercial shellfish and seaweed aquaculture for ecosystem recovery purposes more or less appealing (e.g. degraded species or areas can be subject to protective regulation). However, these areas can also provide critical opportunities to accelerate ecosystem recovery efforts through development of sustained aquaculture production to support delivery of ecosystem services, and the results of this study inform identification of regions where these opportunities are most likely to be realized. Appropriately located through use of regional and local scale spatial planning and management approaches, shellfish and seaweed aquaculture development can play a complementary role to aide governments and communities in achieving conservation, ecosystem recovery or other environmental goals. For example, within the Chesapeake Bay region, the Maryland Department of Natural Resources developed web-accessible, dynamic maps of priority areas for various forms of oyster mariculture to guide management decisions regarding where establishment of leases would most likely yield optimal oyster growth alongside water filtration ecosystem services and while minimizing the likelihood of space use conflict .Concurrent with the rapid, production-centered development of commercial shellfish and seaweed aquaculture sectors, there exists nascent interest in the development of shellfish and seaweed aquaculture for bioremediation, environmental improvement, and other non-consumptive purposes , 39. TheThrough conducting this global-scale spatial analysis, we identified HOMEs for development of shellfish and seaweed aquaculture to support ecosystem recovery and benefit society. These locations of high opportunity, depending on specific environmental, socioeconomic and human health conditions, may benefit from targeted efforts to build in-region technical capacity for shellfish and seaweed aquaculture, improve sector governance, and improve environmental and economic performance of aquaculture to yield benefits to coastal ecosystems and communities. Examples of these targeted efforts include those in Indonesia and Belize where The Nature Conservancy is working with local fishers, government agencies, and NGO partners to build capacity for sustainable seaweed aquaculture sectors . This inAs coastal ecosystems and communities face mounting threats, a more integrated, pragmatic, and market-driven approach to ecosystem recovery and management efforts is increasingly critical. Shellfish and seaweed aquaculture hold great promise as a tool that can play a role in improving the outcomes of these efforts when developed responsibly. The high opportunity marine ecoregions identified in this study represent those areas where targeted governance support and business development efforts by governments, international development organizations, and investors may hold the greatest promise to develop these sectors in a manner that supports positive outcomes for both ecosystems and society.S1 FigDark blue colors indicate marine ecoregions with high amounts of available data to represent factors considered within each spatial analysis scenario.(TIFF)Click here for additional data file.S2 FigHigh (green) to low (red) opportunity marine ecoregions for development of (A) shellfish aquaculture and (B) seaweed aquaculture based on the synthesis of all environmental, socioeconomic, and human health factors  accordin(TIFF)Click here for additional data file.S3 FigThe mean and standard deviation of RAOI scores in each scenario are included.(TIF)Click here for additional data file.S1 TableFor ecoregions where data was not available for certain factors included within a given restorative aquaculture opportunity analysis scenario Figs , the wei(XLSX)Click here for additional data file.S1 Data(XLSX)Click here for additional data file.


On August 8, 2018, the New York City Department of Health and Mental Hygiene notified CDC about two high school students hospitalized for pneumonia of unknown etiology who had recently returned from community service trips constructing houses near Tijuana in Baja California, Mexico. Patients had developed fever 9 and 11 days after travel, followed by rash and lower respiratory symptoms. Symptoms did not improve with multiple courses of antibacterial medications, and the patients subsequently received diagnoses of coccidioidomycosis, a fungal disease commonly known as valley fever.Given the occurrence of severe illness in two young and previously healthy persons, additional case finding was conducted through outreach to the school group and an organization that coordinates service trips, as well as through Epi-X* notices. By October 15, 2018, eight cases of clinically diagnosed valley fever had been reported in four states  in persons who traveled on multiple service trips during June–July 2018 . Four paValley fever is primarily acquired through inhalation of airborne dust or soil containing the spores. Approximately 40% of persons develop influenza-like symptoms 1–3 weeks after exposure. Approximately 5%‒10% of persons develop serious pulmonary problems, and an even smaller percent (1%) of persons develop disseminated disease. The disease is endemic in the southwestern United States, northern Mexico, and parts of Central and South America (The severity of illness and delays in accurate diagnosis observed in this outbreak underscore the importance of obtaining a travel history and considering coccidioidomycosis in persons with respiratory symptoms, with or without rash, who have returned from northern Mexico or areas of the United States where the disease is endemic.


Public Health Laboratories (PHLs) in Puerto Rico did not escape the devastation caused by Hurricane Maria. We implemented a quality management system (QMS) approach to systematically reestablish laboratory testing, after evaluating structural and functional damage. PHLs were inoperable immediately after the storm. Our QMS-based approach began in October 2017, ended in May 2018, and resulted in the reestablishment of 92% of baseline laboratory testing capacity. Here, we share lessons learned from the historic recovery of the largest United States’ jurisdiction to lose its PHL capacity, and provide broadly applicable tools for other jurisdictions to enhance preparedness for public health emergencies. Hurricane Maria hit Puerto Rico in 2017 and resulted in a complete loss of activity of the Public Health Laboratories. Here, the authors discuss the approach taken and tools developed to re-establish activity in these laboratories using a quality management system and the lessons learned in this process. PRDH served a population of more than 3.3 million people before Hurricane Maria, and the storm represented a historic loss of capacity for the most populous jurisdiction in the United States to completely have lost its PHL operations. The PRDH PHL system consists of four facilities across the island, located in the municipalities of San Juan, Arecibo, Mayaguez, and Ponce . Of note, a number of individual laboratories in the central, Mayaguez, and Ponce facilities are under strict regulatory oversight by the Centers for Medicare & Medicaid Services (CMS) as this agency is responsible for the Clinical Laboratory Improvement Amendments (CLIA). However, this agency issued a waiver to regulatory requirements. The PRDH PHL system also includes the Biological and Chemical Emergencies Laboratory (BCEL) and the Newborn Screening Laboratory, both of which are located in San Juan.In September 2017, Hurricane Maria severely damaged the Puerto Rico Department of Health (PRDH) Public Health Laboratories (PHLs), resulting in immediate and long-term impacts on public health services. PHLs serve an integral role in protecting human health by conducting laboratory tests to identify disease outbreaks and monitor the safety of food, water, and the environment. In addition, the Puerto Rico PHLs partner with the Laboratory Response Network , the CDC Laboratory Team (consisting of 23 Spanish-speaking responders from October 2017 through May 2018) worked with laboratory subject matter experts (SMEs) at PRDH and began efforts to reestablish laboratory activities to pre-Hurricane Maria levels in coordination with federal, state, and non-governmental partners. The main goal of this work was to facilitate the reestablishment of full laboratory testing capacity at PRDH. This Perspective describes the significant challenges faced in restoring laboratory functions, capacity, services, and clinical testing in Puerto Rico, the specific efforts that were needed after the event and the lessons learned in this process.1. Briefly, Fig. The team’s approach aligned with principles outlined by the Clinical and Laboratory Standards Institute (CLSI) as laboratory quality system essentials (QSE) Fig. 1. Briefl1. These tools have been made freely available under a Creative Commons Attribution (CC-BY 4.0) license online to assist with enhancing laboratory preparedness efforts (https://figshare.com/s/4f9bf87e55304b5ae577). An important aspect of a quality systems approach to disaster recovery is the identification and implementation of Quality Indicator (QI) assessment2. QIs provide an objective measure to potentially evaluate all critical domains identified in the disaster recovery process. Data from and outcomes associated with those domain assessments may be implemented in a consistent and comparable manner across settings and over time. When assessing the quality of restored laboratory services using QIs, it is important to ensure systematic and consistent data collection and analysis by using a comprehensive set of indicators that addresses all stages of the assessment2.For implementation, we developed tools and integrated them with response and recovery activitiesThe impact on Hurricane Maria on the PRDH PHL’s ranged from tangible, e.g. roof damage, to intangible, including disruption of internal laboratory processes and procedures that are critical for providing services. In Phase 1, after assuring the safety of all the personnel, facilities were assessed to systematically identify the areas of impact and the organization of the response was established. Laboratory assessments were conducted by an interdisciplinary team of CDC laboratory scientists with experience in management of laboratory quality, safety, and CLIA-regulated testing, who represented a variety of subject matter expertise areas. Team members were recruited for overlapping 3-week deployments, in an approach that facilitated a flexible, rapidly mobilizable and sustainable emergency response. The first representatives of the team deployed to Puerto Rico on 12 October 2017, in recognition that rapid needs assessment is foundational to strategic response. Deployment timing was impacted by logistical constraints due to limited access to the island following a natural disaster of the scale of Hurricane Maria. Assessment of laboratory spaces was triaged based on the identification of priority pathogens, as determined by PRDH SME’s. Assessments of spaces critical for restoring testing capacity for these pathogens were completed within 2 weeks of the first deployment. Deployers used an assessment tool previously developed for the baseline assessment of foodborne, waterborne, and environmental laboratory activities. The tool also contained questions about accreditation, licensing, quality and additional questions covering CLIA activities were also added. Subsequent members of the laboratory team assessed remaining laboratory spaces, including those at other PRDH facilities across the island, throughout the month of November. In the weeks following Hurricane Maria, CDC asked the Association of Public Health Laboratories (APHL) to conduct independent assessments of the PRDH facilities during the month of October. Assessments of PRDH facilities were also conducted by the Federal Emergency Management Agency (FEMA).3. While the individual findings from APHL and CDC assessment teams were consistent, this quality-focused approach was developed by CDC deployers to address the need for a prospective, systems-wide evaluation of the impact of the hurricane to facilitate recovery of this complex laboratory network. Multiple barriers to re-establishment of services were identified in the aftermath of Hurricane Maria, including a need for access to uninterrupted municipal power, facility damage, damage to critical equipment and reagents, and challenges with procurement. The Biological and Chemical Emergency Laboratory (BCEL) and Newborn Screening Laboratory sustained minimal damage and service interruptions . However, two laboratory facilities This QSE-based approach facilitated the integration of prospective laboratory assessments with response activities, through the identification and monitoring of inter-dependent laboratory needs. Initial assessments of the laboratory spaces showed that direct damage from water or wind, and indirect damage due to power fluctuations following the storm and subsequent attempts to connect the buildings to generators Table , impacteAs a result of impacted cold storage 12 (86%) of the individual laboratories reported loss of critical reagents. Reagents stored at room temperature also have temperature range requirements, which were challenging to maintain without climate control. Therefore, an initial priority was to mitigate critical laboratory needs in the facilities and safety domain, followed by procurement of reagents and tools necessary for qualification of equipment  and water testing by the Environmental Protection Agency (EPA). Proficiency testing, a method of evaluation by an external regulatory body based on the ability of a laboratory to evaluate a panel of standardized unknown specimens, is a cornerstone of laboratory certification. Laboratory Team members worked with PRDH laboratory SMEs to understand the impact of Hurricane Maria on proficiency and certification timelines, which could potentially result in regulatory non-compliance. This phased approach informed assessment of reagent needs to support quality assurance of clinical, surveillance and environmental testing . In turn, the reactivation of proficiency testing services administered by PRDH had important implications for other public health and clinical laboratories within the jurisdiction, which rely on PRDH central PHL’s to support their own quality assurance programs.In Phase 2, by controlling the process of how equipment was excessed (if damaged) or purchased and inventoried, the response moved quickly into the next phase of restoring local diagnostic and surveillance testing. Maintaining documents and records was key to ensure items were received and qualified and that service and maintenance contracts were procured. Hurricane Maria also impacted procurement. The laboratory team worked with PRDH SME’s to identify vendors ; create purchasing accounts when necessary; verify prices; set the terms of contracts and service agreements; and finally, purchase the goods. The only two delivery routes to Puerto Rico are by air and by sea. Because of disruption in routine shipping systems, optimization of these procedures  was a strategic element of the process.4. The first shipments included essential laboratory items . Later orders included laboratory items that failed quality control checks when PRDH was returned to grid power, as well as those that failed after prolonged exposure to heat and humidity . By 18 May 2018, 226 days into the laboratory response, 92% of the laboratory testing capacity based on the volume of tests run in the previous year could be performed  was key. If nonconforming events occur, they should be managed and used to inform the continual improvement process.5. A template for a sample shipping and tracking database is provided at https://figshare.com/s/4f9bf87e55304b5ae577. In December 2017, two QSE modules covering sample shipping and sample tracking were developed. Analysis of QI, e.g. average sample shipping time (defined as the time a package left PRDH in San Juan until it was received by CDC in Atlanta) from 1.3 days in November to 1.0 days in December demonstrated the impact of tool implementation. The shipping time remained at less than 1.1 days through the duration of the response (until May 2018), with one exception due to adverse weather events in January 2018 that affected air traffic nationwide. The primary reason for improved shipping was due to the reduction in the number of packages delayed or rejected by the courier because of errors in package labeling. As of 18 May 2018, more than 2800 clinical and surveillance samples were shipped from PRDH to partner testing laboratories. CDC tested 75% of the samples shipped, and coordinated the shipping of samples being tested for tuberculosis to partner laboratories in the states of Georgia, Virginia, and Florida. The CDC Foundation and partner organizations like APHL and CDC EOC supplied necessary items to facilitate the sample shipping process, including courier fees and laboratory consumables like biohazard bags, shipping boxes, dry ice, and ice packs.In addition to procurement of critical laboratory supplies, infectious disease testing needed to be reestablished. During the initial response, priority pathogens were identified by PRDH and partner laboratories in the continental US were identified by the CDC Laboratory Team to reestablish interim clinical diagnostic testing and surveillance for those pathogens starting in October 2017. Sample shipping and tracking systems were implemented by the CDC Laboratory Team to facilitate this process and provide quality assuranceThe PRDH facilities that provided testing for priority pathogens were the initial focus, although the overlap in laboratory facilities meant that many of the laboratory concerns were addressed simultaneously. Additional requirements to reestablish laboratory operations included reconnection to the electrical power grid, repair or replacement of air conditioning units, repair of back-up electric generators, mold remediation, re-certification/re-qualification of essential equipment, and further support for existing documentation. Hurricane Maria resulted in extensive losses of high-cost, high-impact electronic laboratory equipment, including analytical instrument computers, printers, cables, and local network/Internet access. One crucial recovery measure implemented was the installation of uninterruptible power source (UPS) towers, which allowed for a controlled shutdown of instruments when generator or grid power was interrupted. Achieving full power status  in the laboratory areas (excluding administrative and office spaces) was coordinated between federal agencies and PRDH. By mid-February 2018, the percent of laboratory areas that achieved full power status increased to more than 80%.https://figshare.com/s/4f9bf87e55304b5ae577 helped us establish priorities for equipment repair or replacement.A final consideration for the recovery phase was the expansion of the QMS already in place at PRDH. The existing QMS provided support toward long-term recovery and complemented PRDH’s emergency preparedness and readiness plans. With the influx of new refrigerators, freezers, and incubators, attendant National Institute of Standards and Technology (NIST)-certified thermometers were needed. Ordering new equipment required measuring available space and making sure surfaces were leveled. Basic items such as a tape measure and a level to perform these tasks were not easily available. It was quickly realized that an Emergency Laboratory Kit needed to be developed that included components required to move or re-qualify equipment and establish whether instruments needed to be excessed and replaced. The collection of equipment listed in the Example Emergency Laboratory Kit that can be found at PHLs are a critical component of emergency public health responses in general. Laboratory activities are integral to confirming environmental, epidemiological and clinical investigations for individuals and vulnerable populations following an emergency event. In order to appropriately respond, health professionals and responders need diagnoses for individual patients as well as syndromic surveillance to detect outbreaks or emerging diseases.https://figshare.com/s/4f9bf87e55304b5ae577 were used during the response described here to help reestablish laboratory testing capacity to 92% within a period of 6 months. Some of the local routine testing at PRDH was resumed starting in December 2017, when the laboratories testing for rabies and influenza surveillance were restored and recertified. The sequential handover was accomplished collaboratively by PRDH staff and the CDC Laboratory Team as laboratory spaces were restored, with assistance from the multidisciplinary partners (including CDC field staff assigned to PRDH) who worked closely across federal agency jurisdictions and geographic boundaries. The reestablishment of testing illustrated in Fig. The mitigation tools developed and available at https://figshare.com/s/4f9bf87e55304b5ae577. The Inventory and Priority Supplies Template and the Sample Shipping and Tracking Log Template are available for laboratory staff and administration to review, edit as appropriate, and implement to help secure their own facilities to support enterprise level preparedness activities. We have also developed a training manual for laboratory responders which proved useful to maintain continuity while deployed staff rotate through, and are demobilized and backfilled. By using a quality management-based, process control approach, the workflows, and templates presented in this Perspective are widely applicable to public health and other laboratory networks that could be damaged by a regional disaster event, or in other emergency circumstances when PHL facilities are compromised or stressed.An additional outcome of this work has been the enhancement of the preparedness of public health laboratory facilities by creating tools to facilitate the reestablishment of services after interruption by an emergency event. Logistical challenges addressed included equipment and reagent delivery delays due to interruption in the transportation chain, and the installation of larger items when building infrastructure was damaged . The resources and templates created during this response are in the public domain, and are available for download at


To assess the possible impacts caused by cooling-water intake system entrainment and impingement losses, populations of six target fish species near power plants on the Ohio River were modeled. A Leslie matrix model was constructed to allow an evaluation of bluegill, freshwater drum, emerald shiner, gizzard shad, sauger, and white bass populations within five river pools. Site-specific information on fish abundance and length-frequency distribution was obtained from long-term Ohio River Ecological Research Program and Ohio River Sanitation Commission (ORSANCO) electrofishing monitoring programs. Entrainment and impingement data were obtained from 316(b) demonstrations previously completed at eight Ohio River power plants. The model was first run under a scenario representative of current conditions, which included fish losses due to entrainment and impingement. The model was then rerun with these losses added back into the populations, representative of what would happen if all entrainment and impingement losses were eliminated. The model was run to represent a 50-year time period, which is a typical life span for an Ohio River coal-fired power plant. Percent changes between populations modeled with and without entrainment and impingement losses in each pool were compared to the mean interannual coefficient of variation (CV), a measure of normal fish population variability. In 6 of the 22 scenarios of fish species and river pools that were evaluated , the projected fish population change was greater than the expected variability of the existing fish population, indicating a possible adverse environmental impact. Given the number of other variables affecting fish populations and the conservative modeling approach, which assumed 100% mortality for all entrained fish and eggs, it was concluded that the likelihood of impact was by no means assured, even in these six cases. It was concluded that in most cases, current entrainment and impingement losses at six Ohio River power plants have little or no effect at the population level.


Health Disparities (HD) are community-based, biomedical challenges in need of innovative contributions from Science, Technology, Engineering and Math (STEM) fields. Surprisingly, STEM professionals demonstrate a persistent lack of HD awareness and/or engagement in both research and educational activities. This project introduced Health Disparities (HD) as technical challenges to incoming undergraduates in order to elevate engineering awareness of HD. The objective was to advance STEM-based, HD literacy and outreach to young cohorts of engineers. Engineering students were introduced to HD challenges in technical and societal contexts as part of Engineering 101 courses. Findings demonstrate that student comprehension of HD challenges increased via joint study of rising health care costs, engineering ethics and growth of biomedical-related engineering areas. Health Disparities (HD) are preventable differences in the incidence, prevalence, mortality and burden of disease on communities targeted by factors such as gender, residence, ethnicity and/or socioeconomic status . HD haveThe interdisciplinary nature of engineering can help decipher many current and developing HD challenges by leveraging engineering underpinnings to integrate technology with fundamental science, clinical therapies and health outcomes. Further, joint biomedical- related engineering ventures have impacted US public policy , health This brief describes a 4-year project undertaken to advance STEM- based HD literacy  and outrThis project was conducted with incoming undergraduate cohorts (first year students and transfers) at the Grove School of Engineering at the City College of New York (CCNY) over 4 years. Students in the introductory engineering course (ENGR 101) were given surveys and assignments to complete, whose results were statistically analyzed using the student’s t-test and post-hoc Tukey test. The overall course goal was to expose new students to potential engineering careers using small projects and assignments that cultivate their requisite technical skills. Each cohort in this study was comprised of 135–155 students, per year, all of whom were declared engineering majors and were predominantly under the age of 25.CCNY heralds the only accredited, public engineering school in New York City, and is the flagship campus of the 24 schools that comprise the City University of New York (CUNY). CCNY is also a Minority Serving Institution  in whichThis project introduced the concepts of health disparities (HD) to incoming students via the required, introductory course in Engineering. This was executed in two parts: (a) Placing HD and STEM fields in the context of US health care costs and (b) Using HD data as part of technical engineering training. Assessment of increased student HD awareness upon course completion was also measured.www.cms.gov). More poignantly, this costly trend has increased dramatically in the current decade and is expected to continue. In complement, data in www.nsf.gov). This academic trend has steadily increased through 2017, where nearly one third of all US baccalaureate degrees were awarded in STEM [Incoming engineering students were introduced to the rising costs of US health care alongside the increasing numbers of STEM majors. As shown in  in STEM .Using this national data, courses discussed unique interdisciplinary opportunities for engineers in health care and policy, as well as introduced the concepts of HD and community-based challenges in global and US health. The second part of the project utilized HD data for technical assignments that developed statistical problem-solving skills needed in engineering professions. Students manipulated and analyzed epidemiological data from select US case studies of well-known HD challenges, e.g. cardiovascular disease , obesityThe project, lastly, measured student awareness of HD challenges and how BME could be expanded with an HD context. Students were asked to provide an answer to the question, ‘Why are challenges in US Health Disparities important?’ at both the beginning and end of the course. As shown in By contrast, The growth of Health Disparities (HD) across different communities of Americans represents a biomedical challenge that has engaged few engineering professionals. Technical curricula lag in introducing HD challenges as opportunities for engineering innovation and impact, despite record numbers of STEM degrees awarded this decade. This brief describes a strategy with which to introduce engineering majors to HD challenges in a technical context. Introductory 101 courses became ideal nucleation sites because HD comprehension requires a technical grasp of statistical analyses fundamental to all engineering experiments. In addition, HD challenges simultaneously introduce contemporary themes within engineering ethics that interface with public policy, generational societal activism  and ABETThe responses from engineering cohorts recorded in this project illustrate two main themes. First, incoming engineers were often unaware of the high cost of health care or the prevalence of HD in the US. This is expected, as students can rely upon their parents for US medical insurance until the age of 25, as a whole are among the healthiest cohorts of Americans, and are minimally exposed to disparities in disease progression and/or burden within their age group . Second,Future projects will develop comprehensive strategies to increase engineering engagement in HD by: (a) Integrating HD data into research and engineering design projects; (b) Incorporating underlying HD medical principles into required STEM courses; and (c) Using HD challenges to improve experimental design procedures. Ambitious programmatic actions include developing an HD-based engineering ethics curriculum and creating an HD certificate program or approved engineering minor in Health Disparities jointly with community and public health programs.Introducing engineering undergraduates to HD literature in joint technical and societal contexts increases student awareness and comprehension of these complex community-based challenges. Early exposure to HD as engineering challenges will help increase the number of HD-related researchers in STEM and incorporate HD into engineering ethics and technical curricula.


Introduction: The incidence of pituitary dysfunction after severe ischemic stroke is unknown, however given the increasing attention to pituitary dysfunction after neurological injuries such as traumatic brain injury, this may represent a novel area of research in stroke.Methods: We perform an arginine and human growth hormone releasing hormone challenge on ischemic stroke patients within a week of symptom onset.Results: Over the study period, 13 patients were successfully tested within a week of stroke . Overall, 9(69%) patients had a poor response, with 7(54%) of these patients meeting the criteria for had human growth hormone deficiency. Other measures of pituitary function were within normal ranges.Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery. Enhancement of recovery after ischemic stroke has been a challenging area, with no intervention being widely adopted to promote recovery in clinical practice. In the search for innovative treatment targets post stroke, we decided to investigate pituitary function after stroke with a focus on human growth hormone (hGH). Other acute brain insults such as traumatic brain injury (TBI) and subarachnoid hemorrhage have demonstrated hypopituitarism in around one quarter of patients shortly after injury . AlthougConsecutive patients presenting to the John Hunter Hospital Emergency Department with first ever clinical diagnosis of an ischemic stroke were assessed for this study. The acute clinical diagnosis was confirmed by multi modal computed tomography (CT) which included CT angiography, CT perfusion and a noncontrast CT. Patients presenting with symptoms typical of transient ischemic attack or stroke mimics such as migraine with aura, seizures, acute confusional states, hypoglycaemia, diabetes, or patients with symptoms related to known prior stroke, or patients with a known history of conversion disorder were excluded from the study.Baseline clinical data recorded included demographics , vascular risk factors , clinical features such as the baseline and 24 h National Institutes of Health Stroke Scale (NIHSS), and premorbid modified Rankin Score (mRS), mRS at discharge and 90 days post stroke.If the patient consented to the study, researchers would organize a fasting blood assessment for the next morning to be taken between 8 and 10 a.m. All enrolled patients underwent growth hormone (GH) provocative test with a GH-releasing-hormone (GHRH) and arginine infusion . GH reseIf the patient was able, study specific assessments were also performed at the time of blood testing and included the Montreal Cognitive Assessment (MoCA) and the NIHSS.From July 2016 to July 2017, 13 patients were enrolled in this prospective study. Median time of testing was 7 days post stroke . All patients with GH deficiency were unable to complete the MoCA assessments.In a cohort of patients with a severe ischemic stroke, we report that there is a considerable number of patients who fulfill criteria for GH deficiency after a provocative test 54–69%) in the first month after stroke. There are limited case series documenting early growth hormone dysfunction after stroke, however, reported pituitary dysfunction may last for up to 12 months (–69% in tThe biological reason behind the observed decline in hGH after stroke, TBI, or subarachnoid hemorrhage is largely unknown. Importantly, pituitary dysfunction after TBI is associated with a worse neurological outcome and increased morbidity and mortality , which mIn conclusion, we report a novel finding of GH deficiency after ischemic stroke, which may ultimately represent a novel treatment to enhance post stroke cognition and recovery. Further studies in stroke survivors are required to understand if those with hGH deficiencies or any other pituitary dysfunction have poorer recovery, and what factors predict which patients are likely to experience hGH deficiency after stroke. Moreover, further studies following endocrine function over time in patients after stroke may be required since pituitary deficiency may be transient in some patients.This study were approved by the Hunter New England Human Research Ethics Committee and each participant provided written informed consent.TL: acquisition of data, critical revision of the manuscript for important intellectual content and study supervision; CG-E: acquisition of data, critical revision of the manuscript for important intellectual content and study supervision; FW: analysis and interpretation, critical revision of the manuscript for important intellectual content and study supervision; LO: critical revision of the manuscript for important intellectual content and study supervision; MN: critical revision of the manuscript for important intellectual content and study supervision; NS: acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content and study supervision; CL: analysis and interpretation,critical revision of the manuscript for important intellectual content and study supervision; MP: Study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content and study supervision; JI: critical revision of the manuscript for important intellectual content and study supervision; AB: Study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content, and study supervision.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The topic of older adults’ information and communication technology (ICT) use looms large because of the beneficial effects of ICT use on physical health, emotional well-being, and social engagement. Previous research has shown that memory performance is also linked with ICT use, but the direction of influence is yet to be determined. Individuals with higher levels of memory function are more likely to use ICT devices, but ICT use may have protective effects on maintaining memory because using technologies includes mental exercises. The current study examined the temporal sequence of ICT use and memory performance, which can provide insight into the causation. Using three waves  from the National Health and Aging Trends Study (NHATS), a total of 4,048 community-dwelling older adults aged 65 and above were selected for the analysis. Memory performance was measured by summing scores of immediate and delayed word recall. Reciprocal 5-year lagged associations between ICT use and memory were examined, while controlling for age, gender, education, racial/ethnic minority status, and depressive symptoms. The final model showed adequate fit indices (CFI = .979 and RMSEA = .038). Word recall significantly predicted ICT use in later years. Reciprocally, greater use of ICT was significantly associated with better memory performance in following years. The effect of ICT use on memory performance was of greater magnitude in comparison with memory as a predictor for ICT use. These results suggest that ICT can have potential benefits for maintaining memory in old age.


The field of Primary Immunodeficiencies (PID) is growing fast. Over 400 diseases are defined and characterized by recurrent or chronic infections, autoimmunity, allergy, inflammation, or cancer as a consequence of genetic alterations affecting the immune system . The oveHumans are genetically heterogeneous, and the environmental characteristics and social habits differ dramatically in the several geographic regions of the world. Consequently, the prevalence and distribution of the nine groups of primary immunodeficiencies vary worldwide, and the clinical profile of a particular PID will also vary.Most of the literature and discoveries about Primary Immunodeficiencies come from North America and Europe and refer to these geographical areas. This Frontiers Research Topic was developed to bring together original clinical and basic research from authors representing various geographical areas to highlight challenges and developments in epidemiology, diagnosis, and treatment of Primary Immunodeficiencies worldwide.Aghamohammadi et al.;de Albuquerque et al.;Goel et al.;Macklin et al.;Pietrucha et al.;Rechavi et al.;Schlechter et al.;Segundo et al.;Slade et al.), 2 Case Reports , 2 Mini-reviews , 6 Reviews , 2 Perspectives , and 1 Opinion (Sorensen).Twenty-two articles are included in this Research Topic, and are categorized into the following types: 9 Original Research (Lee and Lau). Furthermore, it is shown that PID patients excrete poliovirus for extended periods , and that these may form a reservoir that forms a risk to poliovirus eradication strategies . Ruffner et al. provide a comprehensive overview of viral complications of PIDs. On top of infections, vaccination with live strains such as BCG are a major risk for complications in those countries where it is provided, including in India , and these complications are also associated with newly identified genetic causes of PID (de Jesus Nunes-Santos and Rosenzweig).Within the context of epidemiology, several papers present and discuss infectious complications in international cohorts. It is discussed how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections worldwide , and an antibody-deficient cohort in Australia . These complications most frequently involve autoimmunity, gastrointestinal disease, granulomatous inflammation, and malignancy. Disease complications vary even between individuals with the same genetic defect as illustrated by two siblings with RNF168 deficiency, highlighting roles for additional genetic or epidemiological factors . Countries in the Middle East and North Africa (MENA) with high rates of consanguinity face additional challenges , as some autosomal recessive disorders can be unexpectedly frequent and disease presentation can be complicated by other genetic changes.In addition to infectious complications, non-infectious complications are more frequently documented worldwide as exemplified in papers presenting the PID field in India . In developed countries, the implementation of next-generation sequencing technologies has taken flight , and facilitates quick diagnosis such as in the case of X-Linked Moesin-Associated Immunodeficiency  and MAP3K14 deficiency .Diagnostic challenges vary worldwide. Access to genetic genetics in developing countries is often limited, and shipment of patient material can be costly. The use of dried bloodspots for sequence analysis of genomic DNA will be a means to overcome the cost limitation , and many countries worldwide, including Israel, have now adopted it .The most optimal timing of PID diagnosis is before disease presentation and that is aimed at in newborn screening programs. A lot of experience has been obtained with the T cell receptor excision circle (TREC) assay in the USA (Sorensen), and this can result in substantial diagnostic delays . Functional assays for diagnostics require more insights into disease pathogenesis, and this lies at the heart of basic research into PID. Examples included in this Research Topic are examination of STAT phosphorylation upon cytokine receptor engagement , and in vitro models of innate immune responses to Candida .Still, more insights into PID pathogenesis and genetics are needed. Diagnosis of antibody deficiency remains challenging, especially in the context of normal total IgG serum levels (Quinti and Mitrevski), and might warrant the use even beyond antibody deficiency. More recently developed biologicals will hold even more promise over the coming years (Quinti and Mitrevski). Corrective therapy would be ultimate form of treatment, and hematopoietic stem cell transplantation is currently more widely applied in combined immunodeficiencies and in immune dysregulation disorders. Although the rarity of specific PIDs could hamper clinical trials, the genetic definition of disease should provide the best rationale for compassionate access to enable precision medicine.The ultimate focus of the Research Topic concerns treatment of PID. Immunoglobulin replacement therapy is already provided for over 60 years to supplement IgG, but has additional immunomodulatory roles that are still not completely understood .


The burden of osteoporosis, both on the health care system and individuals, is high. Despite this, a high percentage of patients with or at risk of osteoporosis are not identified, screened and treated appropriately. Delivering osteoporosis care to at-risk patients is complicated by a fractured health care delivery system. In this presentation, we present data from interviews with VA clinicians in order to identify challenges of osteoporosis care within the VA health care system. While clinicians reported initiating a range of bone health care delivery interventions, they identified challenges that inhibited long-term sustainability: 1) low prioritization of bone health among national and facility leadership; 2) fragmentation of clinical responsibility and care delivery; and 3) barriers endemic to the osteoporosis care delivery system. Our results indicate that, even within an integrated health care delivery system, significant coordination challenges exist.


Journal of the Medical Library Association (JMLA) had the highest percentage of articles with both librarian and faculty coauthors out of 13 peer-reviewed journals in science, technology, engineering, and medicine librarianship and education between 2005 and 2014. A deeper and updated analysis of JMLA research articles and case studies published between 2008 and 2017 revealed that 29% of articles had both librarian and faculty coauthors. The main topics of librarian-faculty collaboration, as described in these articles, were related to patient and consumer health information and clinical information-seeking and decision-making by health care providers. Most faculty coauthors came from the disciplines of biomedical or health informatics and biostatistics and library and information science. The publication of these articles in the JMLA provides evidence of health sciences librarians’ and information specialists’ ability to collaborate with faculty members to advance the knowledgebase and practice of librarianship and the health sciences.A recent study by Higgins and colleagues reports that the  Journal of the Medical Library Association (JMLA) had the highest percentage (12%) of articles with both librarian and faculty coauthors between 2005 and 2014 [Health Information and Libraries Journal and Medicine Reference Services Quarterly) as opposed to science and engineering journals, suggesting that “medical librarians as a professional group have been accepted by medical faculty and clinicians within research, education, and clinical teams” [Last year, Higgins and colleagues found that out of 13 peer-reviewed journals in science, technology, engineering, and medicine (STEM) librarianship and education, the JMLA, I was thrilled to see the journal at the top of this list, which provided evidence of health sciences librarians’ and information specialists’ ability to collaborate with faculty members to advance the knowledgebase and practice of librarianship and the health sciences. At the same time, however, some questions came to mind: What are the topics of these collaborative articles? What are the most common disciplines of collaborating faculty members? To answer these questions, I asked Higgins and her coauthors to share their data [As the editor of the eir data , they saThe line between being a librarian versus being a faculty member can be fuzzy. For the purpose of this analysis, I defined “librarian” as practicing librarians, library directors, full-time library staff, informationists, information specialists, curators, archivists, National Library of Medicine staff and fellows, or Medical Library Association staff, regardless of whether their positions were tenure-track. I defined “faculty” as nonpractioner professors in library and information science (LIS), professors in any other non-LIS discipline, or physicians. Data visualization was performed using Tableau software .JMLA (n=374) had both librarian and faculty coauthors, whereas 59% (n=222) and 13% (n=50) of such articles had only librarian authors or no librarian authors, respectively. That is, early a third of JMLA articles describing research projects or library-driven initiatives were borne out of collaboration between librarians and faculty members or physicians.Between 2008 and 2017, I found that 29% (n=109) of research articles and case studies published in the JMLA remained fairly stable across this 10-year period despite some year-to-year variation , and the number of article coauthors—regardless of their identity—also held steady over time, with an average of 3 authors per article. The much higher proportion of collaborative articles found in this analysis compared with the previous analysis by Higgins and colleagues [The proportion of librarian-faculty collaborative articles published in the JMLA articles, I categorized each collaborative article by its primary focus. I found that the main topics of collaboration were related to patient and consumer health information (n=22) and clinical information-seeking and decision-making by health care providers (n=20)  . Other tJMLA articles, I classified individual faculty members based on their primary departmental affiliations as provided in the articles or, if not available, professional information discerned through Google searches. Perhaps not surprisingly, I found that most faculty coauthors came from the disciplines of biomedical or health informatics and biostatistics (n=29) and LIS (n=27) (To identify the disciplines of the 167 faculty coauthors of the 109 collaborative S (n=27) . Other cThe results of the present analysis and that of Higgins and colleagues  highlighImportantly, these analyses do not touch upon the undoubtedly large body of literature reflecting librarian-faculty collaborations that appear in medical, information science, and other types of journals  that alsMLA Research Training Institute for Health Sciences Librarians) and to formalize institutional support for research engagement in terms of providing funding, protecting research time, and fostering a “research culture” in libraries [To increase the capability and readiness of health sciences librarians and information specialists to work alongside faculty and physicians as members of interdisciplinary research teams, the profession must continue to provide opportunities for research training and mentorship (e.g., the ibraries . Also, libraries .Finally, congratulations to those health sciences librarians and information specialists who have successfully forged partnerships with faculty or physicians and published the outcomes. Keep up the good work!


In a Policy Forum, Irva Hertz-Picciotto and colleagues review the scientific evidence linking organophosphate pesticides to cognitive, behavioral, and neurological deficits in children and recommend actions to reduce exposures. Widespread use of organophosphate (OP) pesticides to control insects has resulted in ubiquitous human exposures.High exposures to OP pesticides are responsible for poisonings and deaths, particularly in developing countries.Compelling evidence indicates that prenatal exposure at low levels is putting children at risk for cognitive and behavioral deficits and for neurodevelopmental disorders.To protect children worldwide, we recommend the following:Governments phase out chlorpyrifos and other OP pesticides, monitor watersheds and other sources of human exposures, promote use of integrated pest management (IPM) through incentives and training in agroecology, and implement mandatory surveillance of pesticide-related illness.Health professions implement curricula on the hazards from OP pesticides in nursing and medical schools and in continuing medical education courses and educate their patients and the public about these hazards.Agricultural entities accelerate the development of nontoxic approaches to pest control through IPM and ensure the safety of workers through training and provision of protective equipment when toxic chemicals are to be used.Organophosphate (OP) compounds were originally developed as human nerve gas agents during the 1930s–1940s, and some were later adapted as insecticides at lower doses [In the United States, many OP pesticides—including malathion, dichlorvos, azinphos-methyl, and chlorpyrifos—were licensed for insecticidal use before requirements to evaluate human toxicity or ecologic effects were established . BecauseThe most comprehensive global database on recent pesticide use includes information reported by 71 countries in five regions . Annual OP pesticides present a range of health hazards. Here we review the scientific evidence of OP impacts on child neurodevelopment. In addition, we discuss inadequacies in current OP pesticide regulations and present recommendations for urgently needed policy change.Systematic reviews and multiple epidemiologic studies in the US and other countries, spanning diverse populations in both urban and agricultural settings, have linked OP exposures during fetal development with poorer cognitive, behavioral, and social development in children –11. GeneConsistent with the wide range of outcomes reported in human studies, the toxicity of early-life OP pesticides on neurodevelopmental end points has been confirmed in experimental animal studies. Parallel with epidemiologic findings, effects on cognition, motor activity, and social behaviors were repeatedly demonstrated in rodents dosed in early life with concentrations of OPs eliciting little to no inhibition of AChE in the brain ,12. The Since publication of the epidemiologic reviews, a higher likelihood of an ASD diagnosis was observed for children born to women residing within (versus beyond) 1.5 km of OP pesticide applications on agricultural fields; the strongest associations were for chlorpyrifos . AnotherAccurate measurement of exposure is critical in environmental health studies. The OP pesticide studies determined exposure in various ways, ranging from quantification of OP metabolites in maternal urine collected during pregnancy and direct measurement of chlorpyrifos in umbilical cord blood to quantifying nearby pesticide use by geographically linking residential addresses with California’s database of commercial pesticide applications ,21. The Critical to understanding the influences on early child neurodevelopment is the distinction between acute effects after high-level exposures versus sequelae from chronic lower exposures. As noted above, by inhibiting the enzyme AChE, high-level OPs cause acute, in some cases fatal, effects in humans . Indeed,Large quantities of highly hazardous OP pesticides are imported into developing countries. For example, OP pesticides ranked fourth among 24 chemical groups of pesticides imported into Central American countries , for whiAs tragic as these acute poisonings are, an OP pesticide exposure in the absence of overt poisoning does not imply that neurologic damage has not occurred—for both children and adults ). The USHence, AChE inhibition cannot be used as a biomarker to identify neurodevelopmentally harmful OP pesticide exposures. Reliance on AChE inhibition for regulatory purposes obscures the serious threat that OP pesticides pose to early brain development and represents an unscientific and inadequate approach to health risk assessment. In fact, other effects appear likely to mediate the OP toxicity to neuronal systems that is foundational for childhood behavioral and cognitive deficits. Toxicologic evidence implicates OP pesticides in neuroinflammation, protein-kinase C receptor signaling, insulin resistance, dopaminergic and glutamatergic neurotransmission, and interference with DNA synthesis and nuclear transcription factor functioning, mechanisms highly relevant for brain development ,32–34.Indeed, as-yet-undiscovered harm may emerge from further follow-up of those exposed in early life. Outcomes from fetal exposures appear to be persistent, with associations observed into mid- and late childhood. One cohort repeatedly showed deficits in memory, IQ, and attention deficits or ADHD at ages 2, 3, 5, and 7 years, whereas another exhibited deficits in mental development and reasoning in infancy and at ages 6–9 years (reviewed in ). ChildrPesticide regulations vary widely across the globe. As with pesticide usage, no database has consolidated this information for all countries. Within the US, the EPA regulates pesticides under two overlapping statutes—the Federal Food, Drug, and Cosmetic Act (FFDCA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Many of the insecticides banned in the US were initially licensed prior to 1970, when required health and safety assessment was minimal and before the US EPA was formed. As a result of legislation in the 1970s requiring increased health and safety studies, voluntary agreements were reached between manufacturers and the EPA to cancel or phase out registrations for some pesticides, including 18 OP insecticides.In 1996, the Food Quality Protection Act (FQPA) amended FIFRA and FFDCA by requiring the EPA to include additional safety factors to protect children because of their greater exposures and heightened susceptibility . ChildreAfter passage of the FQPA, OP pesticide use across all market sectors declined by over 70%, from 70 million pounds per year (lbs/yr) in 2000 to about 20 million lbs/yr in 2012 (the most recent available data) . By 2002In 2016, the EPA concluded that exposure to chlorpyrifos—the most commonly used OP insecticide in the US—from either food or drinking water alone could lead to unacceptably high population exposures and determined that some reproductive-aged women, infants, and children consumed levels of chlorpyrifos substantially above the acceptable level for these vulnerable life stages . The EPAIn 2014, the American Academy of Pediatrics called for pediatricians and governments to recognize and reduce pesticide exposures through education, pesticide labeling, public health surveillance, and regulatory action . In 2016We recommend the following actions by governments:National and state or provincial governments, globally: phase out use of all OPs in agriculture;National and state or provincial governments, globally: ban nonagricultural use of all OPs, including household products;US EPA: revoke all food tolerances for chlorpyrifos, as the agency previously proposed;US EPA and state governments: phase out the use of all other OPs in agriculture;US EPA: ban nonagricultural pest control uses of the few remaining OPs;In the interim, national, state, and local agencies: take steps to reduce human exposure ;National, state, and local agencies: conduct regular monitoring of watersheds to ensure OPs do not continue to pollute lakes, rivers, and streams, including those that are sources of drinking water, and implement targeted monitoring of drinking water;National and state agencies: establish an effective comprehensive pesticide use and illness reporting program either nationally or through coordinated statewide programs.We recommend that medical schools, public health programs, and healthcare associations:organize continuing medical education courses to educate healthcare providers on both acute and chronic effects of exposures to toxic chemicals, including how to recognize and treat children who received high OP exposures; how to advise pregnant women and parents of young children on steps they can take to avoid pesticide exposures from lice, flea, and tick treatments , lawn aneducate health providers on the necessary reporting of pesticide poisonings to state surveillance;encourage schools of nursing and medicine to incorporate curricula on environmental hazards that include pesticides and medical boards to include environmental health in their examinations.We recommend that agricultural entities:provide enhanced training for workers, in the most appropriate languages and at relevant educational levels, on the handling and application of pesticides and on the worker protection standards. In the US, this means EPA Worker Protection Standards training at the required frequency;educate workers on how to avoid take-home exposures to their families;institute environmentally friendly approaches to control pests—integrated pest management (IPM)—with a goal to eliminate or minimize toxic chemicals in our food sources.Exemplary actions at various governmental levels have been taken. At the multinational level the EU chose to not approve close to 200 pesticides, of which over 20 are OPs, and multiple individual countries have instituted bans on OPs such as dichlorvos, methamidophos, and methyl parathion . In the In reducing OP pesticide usage, toxic effects from substitute or replacement chemicals require scrutiny. Pyrethroid pesticides have replaced OPs as the main class of insecticides in residential pest control products, but recent rodent laboratory studies and epidemiologic studies suggest that prenatal pyrethroid pesticide exposures may also increase the risk of adverse neurodevelopment and behaviors and negative emotions ,52–54. NWhat are the alternatives, if synthetic pesticides other than OPs are also neurotoxic?Bacillus thuringiensis to control Lepidoptera) [Agriculture represents the vast majority of OP pesticide use, which includes both crop and livestock production. Widespread implementation of IPM is needed to reduce this use. IPM is a reduced-risk pest management strategy that emphasizes inspection, monitoring, prevention, and pest control using the least toxic methods including (agri)cultural practices such as intercropping , crop rotation, and cover crops ; physical controls such as traps or bug vacuums; habitat management that encourages beneficial insects; and biological control, such as the release of parasitic wasps to control aphids, with pesticides used only as a last resort. When used, least-toxic pesticides are chosen first, such as materials approved for organic farming  .While IPM strategies do not, in principle, forbid the use of OP and other neurotoxic pesticides, these higher-risk materials serve as a last resort and should be applied in a way that protects human and environmental health. That most crops produced with OP pesticides are also produced organically provides compelling evidence that OP pesticides are not essential . Some rePublic health, a second use of OP pesticides, represents a small fraction of their applications. For example, OP pesticides are used for mosquito and other vector control to prevent vector-borne diseases such as Zika virus or West Nile virus. We do not recommend abrupt changes in pest management that would increase the risk of exposure to these viruses. We do advocate increased funding for better understanding of the ecology and biology of these and other vectors and the diseases they spread and alternative methods to control them without the use of OP or other neurotoxic pesticides. The historical example of the Mediterranean fruit fly in California, a serious invasive agricultural pest, provides a model for application to disease vectors. In the early 1990s, state officials used helicopters to spray malathion over residential areas where over 2 million people resided . SubsequStructural, indoor, and landscape pesticide applications, the third category of OP uses, can result in high exposures. Dichlorvos, an OP already banned in many countries, is still permitted indoors by the US government for flying insects. Similarly, malathion is still sold for landscape and garden use. Given risks of adverse health effects due to chronic, low-level exposures and reported acute poisoning of consumers in the US , we recoTo preserve health and sustainability, both indoor and outdoor pest management must ultimately rely on nontoxic or less toxic alternatives; simultaneously, agriculture needs stronger support to move towards a systems approach that minimizes use of neurotoxic pesticides while providing healthy food and economic sustainability for farmers. The Report on the Right to Food by the Special Rapporteur to the UN General Assembly articulates a similar philosophy: in order to successfully reduce or eliminate use of hazardous pesticides, the international community’s efforts will need to address the ecologic, social, and economic factors currently embedded in agricultural policies. At the national level, this will require challenging agrochemical-dependent farming to restructure and seek the safest feasible alternatives . We joinS1 FigMap created with mapchart.net. OP, organophosphate.Darker shading indicates greater usage per 1,000 square km. Gray shading indicates that no data were available during that time period. For countries with data available for some but not all years during 2010–2015, the available data within that period were used. Source for US data was ; and for(TIF)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.S2 Text(DOCX)Click here for additional data file.S3 Text(DOCX)Click here for additional data file.S4 Text(DOCX)Click here for additional data file.