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BACKGROUND: Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future. DESIGN: The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field. RESULTS: Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues. CONCLUSIONS: We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.
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Hematología , Receptores Quiméricos de Antígenos , Acreditación , Adulto , Médula Ósea , Humanos , Inmunoterapia Adoptiva , Receptores de Antígenos de Linfocitos TRESUMEN
The atmosphere is host to a complex electric environment, ranging from a global electric circuit generating fluctuating atmospheric electric fields to local lightning strikes and ions. While research on interactions of organisms with their electrical environment is deeply rooted in the aquatic environment, it has hitherto been confined to interactions with local electrical phenomena and organismal perception of electric fields. However, there is emerging evidence of coupling between large- and small-scale atmospheric electrical phenomena and various biological processes in terrestrial environments that even appear to be tied to continental waters. Here, we synthesize our current understanding of this connectivity, discussing how atmospheric electricity can affect various levels of biological organization across multiple ecosystems. We identify opportunities for research, highlighting its complexity and interdisciplinary nature and draw attention to both conceptual and technical challenges lying ahead of our future understanding of the relationship between atmospheric electricity and the organization and functioning of biological systems.
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Ecosistema , Electricidad , AtmósferaRESUMEN
There is an increasing interest to study the interactions between atmospheric electrical parameters and living organisms at multiple scales. So far, relatively few studies have been published that focus on possible biological effects of atmospheric electric and magnetic fields. To foster future work in this area of multidisciplinary research, here we present a glossary of relevant terms. Its main purpose is to facilitate the process of learning and communication among the different scientific disciplines working on this topic. While some definitions come from existing sources, other concepts have been re-defined to better reflect the existing and emerging scientific needs of this multidisciplinary and transdisciplinary area of research.
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Biología , ElectricidadRESUMEN
OBJECTIVES: To describe a cross-border foodborne outbreak of Shigella sonnei that occurred in Ireland and Northern Ireland (NI) in December 2016 whilst also highlighting the valuable roles of sales data and international collaboration in the investigation and control of this outbreak. STUDY DESIGN: A cross-border outbreak control team was established to investigate the outbreak. METHODS: Epidemiological, microbiological, and environmental investigations were undertaken. Traditional analytical epidemiological studies were not feasible in this investigation. The restaurant chain provided sales data, which allowed assessment of a possible increased risk of illness associated with exposure to a particular type of heated food product (product A). RESULTS: Confirmed cases demonstrated sole trimethoprim resistance: an atypical antibiogram for Shigella isolates in Ireland. Early communication and the sharing of information within the outbreak control team facilitated the early detection of the international dimension of this outbreak. A joint international alert using the European Centre for Disease Control's confidential Epidemic Intelligence Information System for Food- and Waterborne Diseases and Zoonoses (EPIS-FWD) did not reveal further cases outside of the island of Ireland. The outbreak investigation identified that nine of thirteen primary case individuals had consumed product A from one of multiple branches of a restaurant chain located throughout the island of Ireland. Product A was made specifically for this chain in a food production facility in NI. S. sonnei was not detected in food samples from the food production facility. Strong statistical associations were observed between visiting a branch of this restaurant chain between 5 and 9 December 2016 and eating product A and developing shigellosis. CONCLUSIONS: This outbreak investigation highlights the importance of international collaboration in the efficient identification of cross-border foodborne outbreaks and the value of using sales data as the analytical component of such studies.
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Brotes de Enfermedades/estadística & datos numéricos , Disentería Bacilar/epidemiología , Enfermedades Transmitidas por los Alimentos/epidemiología , Shigella sonnei , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Comercio/economía , Brotes de Enfermedades/economía , Disentería Bacilar/economía , Disentería Bacilar/microbiología , Femenino , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/economía , Enfermedades Transmitidas por los Alimentos/microbiología , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Irlanda del Norte/epidemiología , Restaurantes , Adulto JovenRESUMEN
Titanium dioxide nanoparticles (TiO2NP) are increasingly released in soil ecosystems, while there is limited understanding of the impacts of TiO2NP on soil bacterial communities. Here we investigated the effects of TiO2NP on the taxonomic composition and functional profile of a soil bacterial community over a 60-day exposure period. In short-term exposure (1-day), contradictory effects on the taxonomic composition of soil bacterial communities were found after exposure to a low realistic environmental concentration of TiO2NP at 1â¯mg/kg as compared to the effects induced by medium and high concentrations of TiO2NP at 500 and 2000â¯mg/kg. After long-term exposure (60-day), the negative effects of TiO2NP at the low concentration disappeared, and the inhibition by TiO2NP of the abundance of core taxa was enhanced along with increasing exposure concentrations. However, although significant alterations were observed in the taxonomic composition over time and exposure concentrations, no significant change was observed in the community functional profile as well as enzyme activity after 60-day exposure, indicating that functional redundancy likely contributed to the bacterial community tolerance after the exposure to TiO2NP. Our study highlighted the importance of assessing bacterial community compositional and functional responses in assessing the environmental risk of nanoparticles on soil ecosystems.
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Nanopartículas , Microbiología del Suelo , Suelo , Titanio/análisis , EcosistemaRESUMEN
Metal-based engineered nanomaterials (ENMs) are known to affect bacterial processes and metabolic activities. While testing their negative effects on biological components, studies traditionally rely on initial exposure concentrations and thereby do not take into consideration the dynamic behavior of ENMs that ultimately determines exposure and toxicity (e.g. ion release). Moreover, functional responses of soil microbial communities to ENMs exposure can be caused by both the particulate forms and the ionic forms, yet their relative contributions remain poorly understood. Therefore, we investigated the dynamic changes of exposure concentrations of three different types of ENMs (nano-ZnO, -Cu and -Pb) and submicron particles (SMPs) in relation to their impact on the capacity of soil bacterial communities to utilize carbon substrates. The different ENMs were chosen to differ in dissolution potential. The dynamic exposures of ENMs were considered using a time weighted average (TWA) approach. The joint toxicity of the particulate forms and the ionic forms of ENMs was evaluated using a response addition model. Our results showed that the effect concentrations of spherical nano-ZnO, -Cu and SMPs, and Pb-based perovskites expressed as TWA were lower than expressed as initial concentrations. Both particulate forms and ionic forms of spherical 18nm, 43nm nano-ZnO and 50nm, 100nm nano-Cu contribute to the overall response at the EC50 levels. The particulate forms for 150nm, 200nm and 900nm ZnO SMPs and rod-shaped 78nm nano-Cu mainly affected the soil microbial metabolic potential, while the Cu ions released from spherical 25nm nano-Cu, 500nm Cu SMPs and Pb ions released from perovskites mainly described the effects to bacterial communities. Our results indicate that the dynamic exposure of ENMs and relative contributions of particles and ions require consideration in order to pursue a naturally realistic assessment of environmental risks of metal-based ENMs.
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Cobre/análisis , Plomo/análisis , Nanopartículas/análisis , Microbiología del Suelo , Contaminantes del Suelo/análisis , Óxido de Zinc/análisis , Compuestos de Calcio/química , Carbono/metabolismo , Cobre/toxicidad , Iones , Plomo/toxicidad , Consorcios Microbianos/efectos de los fármacos , Nanopartículas/toxicidad , Países Bajos , Óxidos/química , Tamaño de la Partícula , Suelo/química , Contaminantes del Suelo/toxicidad , Titanio/química , Óxido de Zinc/toxicidadRESUMEN
The effect of celebrity diagnosis on public awareness of health conditions has already been well documented. In October 2014, Bono, the lead singer with U2, revealed publicly for the first time that he has glaucoma. This study aimed to analyze the impact of Bono's announcement on public awareness of glaucoma using Google Search trends as an indicator of public interest in the disease. Google Trends was used to examine Google Search activity for the term 'Glaucoma' between 2009 and 2015 in both Ireland and the United Kingdom. Trend analyses were performed using Microsoft Excel Version 14.3.5. Increased Google Search activity for 'Glaucoma' in October 2014 was found in both Ireland and the United Kingdom. A five-fold increase from the mean Google Search activity for this term was found in Ireland and a two-fold increase from the mean Google Search activity for this term was found in the United Kingdom. No such increase in Google Search activity occurred during each country's 2014 Glaucoma Awareness week. Google Trends is useful in medical research as a means of assessing public awareness of, and/or interest in, health related topics. Current approaches to glaucoma related health promotion in both Ireland and the United Kingdom have failed to yield an increase in on-line Google Search activity. While there was an increase in interest in glaucoma it is unclear whether this led to an increase in health seeking behaviour.
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Información de Salud al Consumidor/estadística & datos numéricos , Personajes , Glaucoma , Conductas Relacionadas con la Salud , Internet/estadística & datos numéricos , Música , Concienciación , Información de Salud al Consumidor/tendencias , Humanos , Internet/tendencias , Irlanda , Masculino , Reino UnidoRESUMEN
BACKGROUND: We compared the effectiveness and cost of a pain screening and treatment program, with usual care in head and neck cancer patients with significant pain. METHODS: Patients were screened for the presence of pain and then randomly assigned to either an intervention group, consisting of a pain treatment protocol and an education program, or to usual care. Primary outcome was change in the Pain Severity Index (PSI) over three months. RESULTS: We screened 1074 patients of whom 156 were randomized to either intervention or usual care. Mean PSI was reduced over three months in both groups, with no significant difference between the two groups. The Pain Management Index (PMI) at three months, was significantly improved in the intervention group compared with usual care (P<0.001), as was Patient Satisfaction (mean difference in scores was statistically significant: -0.30 [-0.60 to -0.15]). All subjects reported clinically significant levels of anxiety and depression throughout the study. Treatment costs were significantly higher for intervention (mean=£400) compared with usual care (£200), with a low likelihood of being cost-effective. CONCLUSIONS: There was no difference in the Pain Severity Index between the two groups. However there were significant improvements in the intervention group in patient satisfaction and PMI. The pain screening process itself was effective. Sufficient benefit was demonstrated as a result of the intervention to allow continued development of pain treatment pathways, rather than allowing pain treatment to be left to nonformalised ad hoc arrangements.
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Protocolos Clínicos , Neoplasias de Cabeza y Cuello/complicaciones , Manejo del Dolor/métodos , Dolor/diagnóstico , Dolor/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias de Cabeza y Cuello/economía , Costos de la Atención en Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Dolor/economía , Manejo del Dolor/economía , Educación del Paciente como Asunto/economía , Educación del Paciente como Asunto/métodos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
A 53-year-old man took his own life while receiving biological therapy with the tumour necrosis factor-α inhibitor adalimumab for severe psoriasis. The patient had a psychiatric history and a 32-year history of variable unstable psoriasis. Reported suicide in patients with psoriasis receiving adalimumab is rare (only one other reported case). It is important, however, to recognize the effects of skin disease on the mental health of vulnerable patients receiving biological agents. Patients will benefit from a more holistic approach that includes both dermatological and psychological assessment and treatment.
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Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Productos Biológicos/efectos adversos , Trastorno Depresivo/etiología , Psoriasis , Suicidio , Adalimumab , Dermatología , Humanos , Masculino , Persona de Mediana Edad , Rol del Médico , Psoriasis/tratamiento farmacológico , Psoriasis/psicología , Factores de RiesgoRESUMEN
The use of agrochemicals is increasingly recognized as interfering with pollination services due to its detrimental effects on pollinators. Compared to the relatively well-studied chemical toxicity of agrochemicals, little is known on how they influence various biophysical floral cues that are used by pollinating insects to identify floral rewards. Here, we show that widely used horticultural and agricultural synthetic fertilizers affect bumblebee foraging behavior by altering a complex set of interlinked biophysical properties of the flower. We provide empirical and model-based evidence that synthetic fertilizers recurrently alter the magnitude and dynamics of floral electrical cues, and that similar responses can be observed with the neonicotinoid pesticide imidacloprid. We show that biophysical responses interact in modifying floral electric fields and that such changes reduce bumblebee foraging, reflecting a perturbation in the sensory events experienced by bees during flower visitation. This unveils a previously unappreciated anthropogenic interference elicited by agrochemicals within the electric landscape that is likely relevant for a wide range of chemicals and organisms that rely on naturally occurring electric fields.
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The atmosphere hosts multiple sources of electric charge that influence critical processes such as the aggregation of droplets and the removal of dust and aerosols. This is evident in the variability of the atmospheric electric field. Whereas these electric fields are known to respond to physical and geological processes, the effect of biotic sources of charge has not hitherto been considered. Here, we combine theoretical and empirical evidence to demonstrate that honeybee swarms directly contribute to atmospheric electricity, in proportion to the swarm density. We provide a quantitative assessment of this finding, by comparing the electrical contribution of various swarming insect species with common abiotic sources of charge. This reveals that the charge contribution of some insect swarms will be comparable with that of meteorologically induced variations. The observed transport of charge by insects therefore demonstrates an unexplored role of biogenic space charge for physical and ecological processes in the atmosphere.
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Humans alter the environment at unprecedented rates through habitat destruction, nutrient pollution and the application of agrochemicals. This has recently been proposed to act as a potentially significant driver of pathogen-carrying mosquito species (disease vectors) that pose a health risk to humans and livestock. Here, we use a unique set of locations along a large geographical gradient to show that landscapes disturbed by a variety of anthropogenic stressors are consistently associated with vector-dominated mosquito communities for a wide range of human and livestock infections. This strongly suggests that human alterations to the environment promote the presence and abundance of disease vectors across large spatial extents. As such, it warrants further studies aimed at unravelling mechanisms underlying vector prevalence in mosquito communities, and opens up new opportunities for preventative action and predictive modelling of vector borne disease risks in relation to degradation of natural ecosystems.
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Culicidae/clasificación , Culicidae/crecimiento & desarrollo , Ecosistema , Actividades Humanas/estadística & datos numéricos , Malaria/transmisión , Mosquitos Vectores/patogenicidad , Densidad de Población , Animales , Biodiversidad , Humanos , Malaria/epidemiología , Malaria/parasitología , SudáfricaRESUMEN
BACKGROUND: Mosquito population dynamics are driven by large-scale (e.g. climatological) and small-scale (e.g. ecological) factors. While these factors are known to independently influence mosquito populations, it remains uncertain how drivers that simultaneously operate under natural conditions interact to influence mosquito populations. We, therefore, developed a well-controlled outdoor experiment to assess the interactive effects of two ecological drivers, predation and nutrient availability, on mosquito life history traits under multiple temperature regimes. METHODS: We conducted a temperature-controlled mesocosm experiment in Kruger National Park, South Africa, with the yellow fever mosquito, Aedes aegypti. We investigated how larval survival, emergence and development rates were impacted by the presence of a locally-common invertebrate predator (backswimmers Anisops varia Fieber (Notonectidae: Hemiptera), nutrient availability (oligotrophic vs eutrophic, reflecting field conditions), water temperature, and interactions between each driver. RESULTS: We observed that the effects of predation and temperature both depended on eutrophication. Predation caused lower adult emergence in oligotrophic conditions but higher emergence under eutrophic conditions. Higher temperatures caused faster larval development rates in eutrophic but not oligotrophic conditions. CONCLUSIONS: Our study shows that ecological bottom-up and top-down drivers strongly and interactively govern mosquito life history traits for Ae. aegypti populations. Specifically, we show that eutrophication can inversely affect predator-prey interactions and mediate the effect of temperature on mosquito survival and development rates. Hence, our results suggest that nutrient pollution can overrule biological constraints on natural mosquito populations and highlights the importance of studying multiple factors.
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Aedes/fisiología , Eutrofización , Aedes/crecimiento & desarrollo , Animales , Femenino , Rasgos de la Historia de Vida , Masculino , Nutrientes , Conducta Predatoria , TemperaturaRESUMEN
The Earth's subsurface represents a complex electrochemical environment that contains many electro-active chemical compounds that are relevant for a wide array of biologically driven ecosystem processes. Concentrations of many of these electro-active compounds within Earth's subsurface environments fluctuate during the day and over seasons. This has been observed for surface waters, sediments and continental soils. This variability can affect particularly small, relatively immobile organisms living in these environments. While various drivers have been identified, a comprehensive understanding of the causes and consequences of spatio-temporal variability in subsurface electrochemistry is still lacking. Here we propose that variations in atmospheric electricity (AE) can influence the electrochemical environments of soils, water bodies and their sediments, with implications that are likely relevant for a wide range of organisms and ecosystem processes. We tested this hypothesis in field and laboratory case studies. Based on measurements of subsurface redox conditions in soils and sediment, we found evidence for both local and global variation in AE with corresponding patterns in subsurface redox conditions. In the laboratory, bacterial respiratory responses, electron transport activity and H2S production were observed to be causally linked to changes in atmospheric cation concentrations. We argue that such patterns are part of an overlooked phenomenon. This recognition widens our conceptual understanding of chemical and biological processes in the Earth's subsurface and their interactions with the atmosphere and the physical environment.
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Plastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity.
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Nanopartículas/toxicidad , Poliestirenos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/fisiología , Animales , Animales Modificados Genéticamente , Metabolismo Energético/efectos de los fármacos , Glucosa/metabolismo , Hidrocortisona/metabolismo , Larva/efectos de los fármacos , Larva/fisiología , Actividad Motora/efectos de los fármacos , Mutación , Plásticos/toxicidad , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Distribución Tisular , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Adequate predictions of mosquito-borne disease risk require an understanding of the relevant drivers governing mosquito populations. Since previous studies have focused mainly on the role of temperature, here we assessed the effects of other important ecological variables (predation, nutrient availability, presence of conspecifics) in conjunction with the role of temperature on mosquito life history parameters. We carried out two mesocosm experiments with the common brown house mosquito, Culex pipiens, a confirmed vector for West Nile Virus, Usutu and Sindbis, and a controphic species; the harlequin fly, Chironomus riparius. The first experiment quantified interactions between predation by Notonecta glauca L. (Hemiptera: Notonectidae) and temperature on adult emergence. The second experiment quantified interactions between nutrient additions and temperature on larval mortality and adult emergence. Results indicate that 1) irrespective of temperature, predator presence decreased mosquito larval survival and adult emergence by 20-50%, 2) nutrient additions led to a 3-4-fold increase in mosquito adult emergence and a 2-day decrease in development time across all temperature treatments, 3) neither predation, nutrient additions nor temperature had strong effects on the emergence and development rate of controphic Ch. riparius. Our study suggests that, in addition to of effects of temperature, ecological bottom-up (eutrophication) and top-down (predation) drivers can have strong effects on mosquito life history parameters. Current approaches to predicting mosquito-borne disease risk rely on large-scale proxies of mosquito population dynamics, such as temperature, vegetation characteristics and precipitation. Local scale management actions, however, will require understanding of the relevant top-down and bottom-up drivers of mosquito populations.
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Culex/fisiología , Eutrofización , Conducta Predatoria , Temperatura , Animales , Chironomidae/fisiología , Chironomidae/virología , Culex/crecimiento & desarrollo , Culex/virología , Larva/fisiología , Control de Mosquitos/métodos , Mosquitos Vectores/fisiología , Dinámica Poblacional , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/transmisión , Fiebre del Nilo Occidental/virología , Virus del Nilo Occidental/fisiologíaRESUMEN
Agricultural ditches host a diverse community of species. These species often are unwarrantedly exposed to fertilizers and a wide-array of pesticides (hereafter: agrochemicals). Standardized ecotoxicological research provides valuable information to predict whether these pesticides possibly pose a threat to the organisms living within these ditches, in particular macro-invertebrates. However, knowledge on how mixtures of these agrochemicals affect macro-invertebrates under realistic abiotic conditions and with population and community complexity is mostly lacking. Therefore we examined here, using a full factorial design, the population responses of macroinvertebrate species assemblages exposed to environmentally relevant concentrations of three commonly used agrochemicals (for 35days) in an outdoor experiment. The agrochemicals selected were an insecticide (imidacloprid), herbicide (terbuthylazine) and nutrients (NPK), all having a widespread usage and often detected together in watersheds. Effects on species abundance and body length caused by binary mixture combinations could be described from single substance exposure. However, when agrochemicals were applied as tertiary mixtures, as they are commonly found in agricultural waters, species' abundance often deviated from expectations made based on the three single treatments. This indicates that pesticide-mixture induced toxicity to population relevant endpoints are difficult to extrapolate to field conditions. As in agricultural ditches often a multitude (approx. up to 7) of agrochemicals residues are detected, we call other scientist to verify the ecological complexity of non-additive induced shifts in natural aquatic invertebrate populations and aquatic species assemblages.
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Nanoplastic debris is currently expected to be ubiquitously distributed in aquatic environments and an emerging environmental issue affecting organisms across trophic levels. While ingestion of particles receives most attention, other routes of uptake and cellular accumulation remain unexplored. Here, the planktonic filter feeder Daphnia magna was used to track routes of uptake and target tissues of polystyrene nanoparticles (PSNPs). A sublethal concentration of 5 mg L-1 fluorescent PSNPs (25 nm) was used to monitor accumulation in adult animals as well as their embryos in the open brood pouch. A time series throughout embryonic development within the brood pouch revealed accumulation of PSNP in or on lipophilic cells in the early stages of embryonic development while the embryo is still surrounded by a chorion and before the beginning of organogenesis. In contrast, PSNP particles were neither detected in the gut epithelium nor in lipid droplets in adults. An ex vivo exposure of embryos to PSNP demonstrated a similar accumulation of PSNP in or on lipophilic cells, illustrating the likelihood of brood pouch-mediated PSNP uptake by embryos. By demonstrating embryo PSNP uptake via the brood pouch, data presented here give novel insights in bioaccumulation of nanoparticles and likely other lipophilic contaminants. Since this uptake route can occur within a diverse array of aquatic organisms, this study warrants consideration of brood pouch-mediated accumulation in efforts studying the hazards and risks of nanoparticle contamination.