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Microeukaryotes are key contributors to marine carbon cycling. Their physiology, ecology, and interactions with the chemical environment are poorly understood in offshore ecosystems, and especially in the deep ocean. Using the Autonomous Underwater Vehicle Clio, microbial communities along a 1050 km transect in the western North Atlantic Ocean were surveyed at 10-200 m vertical depth increments to capture metabolic signatures spanning oligotrophic, continental margin, and productive coastal ecosystems. Microeukaryotes were examined using a paired metatranscriptomic and metaproteomic approach. Here we show a diverse surface assemblage consisting of stramenopiles, dinoflagellates and ciliates represented in both the transcript and protein fractions, with foraminifera, radiolaria, picozoa, and discoba proteins enriched at >200 m, and fungal proteins emerging in waters >3000 m. In the broad microeukaryote community, nitrogen stress biomarkers were found at coastal sites, with phosphorus stress biomarkers offshore. This multi-omics dataset broadens our understanding of how microeukaryotic taxa and their functional processes are structured along environmental gradients of temperature, light, and nutrients.
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Dinoflagelados , Ecosistema , Agua de Mar , Océano Atlántico , Dinoflagelados/metabolismo , Dinoflagelados/genética , Cilióforos/genética , Cilióforos/metabolismo , Transcriptoma , Estramenopilos/genética , Estramenopilos/metabolismo , Ciclo del Carbono , Nitrógeno/metabolismo , Proteómica/métodosRESUMEN
Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu-cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow-up of 13.3 months, median progression-free survival (PFS) for infused patients was 21 months (10.1-NA) with a 6- and 12-month PFS of 82% (95% confidence interval [CI], 71-89) and 62% (95% CI, 49-73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non-relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA-2 and other real-world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.
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Ocean spring phytoplankton blooms are dynamic periods important to global primary production. We document vertical patterns of a diverse suite of eukaryotic algae, the prasinophytes, in the North Atlantic Subtropical Gyre with monthly sampling over four years at the Bermuda Atlantic Time-series Study site. Water column structure was used to delineate seasonal stability periods more ecologically relevant than seasons defined by calendar dates. During winter mixing, tiny prasinophytes dominated by Class II comprise 46 ± 24% of eukaryotic algal (plastid-derived) 16S rRNA V1-V2 amplicons, specifically Ostreococcus Clade OII, Micromonas commoda, and Bathycoccus calidus. In contrast, Class VII are rare and Classes I and VI peak during warm stratified periods when surface eukaryotic phytoplankton abundances are low. Seasonality underpins a reservoir of genetic diversity from multiple prasinophyte classes during warm periods that harbor ephemeral taxa. Persistent Class II sub-species dominating the winter/spring bloom period retreat to the deep chlorophyll maximum in summer, poised to seed the mixed layer upon winter convection, exposing a mechanism for initiating high abundances at bloom onset. Comparisons to tropical oceans reveal broad distributions of the dominant sub-species herein. This unparalleled window into temporal and spatial niche partitioning of picoeukaryotic primary producers demonstrates how key prasinophytes prevail in warm oceans.
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ABSTRACT: Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly diagnosed CD20+ B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560 mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline International Prognostic Index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] immunochemotherapy, with ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11 of 38 patients (29%; 95% confidence interval [CI], 15-46). This did not reach the prespecified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%; 95% CI, 44-76), and 2-year overall survival (76%; 95% CI, 63-91). Adverse events were mostly hematological, gastrointestinal, and infective. Although TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered at www.clinicaltrials.gov as #ISRCTN32667607.
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Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Trastornos Linfoproliferativos , Piperidinas , Rituximab , Humanos , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/administración & dosificación , Persona de Mediana Edad , Femenino , Masculino , Adenina/análogos & derivados , Adenina/uso terapéutico , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/etiología , Anciano , Adulto , Rituximab/efectos adversos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Órganos/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/uso terapéutico , Estudios Prospectivos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/administración & dosificaciónRESUMEN
Iron is important in regulating the ocean carbon cycle1. Although several dissolved and particulate species participate in oceanic iron cycling, current understanding emphasizes the importance of complexation by organic ligands in stabilizing oceanic dissolved iron concentrations2-6. However, it is difficult to reconcile this view of ligands as a primary control on dissolved iron cycling with the observed size partitioning of dissolved iron species, inefficient dissolved iron regeneration at depth or the potential importance of authigenic iron phases in particulate iron observational datasets7-12. Here we present a new dissolved iron, ligand and particulate iron seasonal dataset from the Bermuda Atlantic Time-series Study (BATS) region. We find that upper-ocean dissolved iron dynamics were decoupled from those of ligands, which necessitates a process by which dissolved iron escapes ligand stabilization to generate a reservoir of authigenic iron particles that settle to depth. When this 'colloidal shunt' mechanism was implemented in a global-scale biogeochemical model, it reproduced both seasonal iron-cycle dynamics observations and independent global datasets when previous models failed13-15. Overall, we argue that the turnover of authigenic particulate iron phases must be considered alongside biological activity and ligands in controlling ocean-dissolved iron distributions and the coupling between dissolved and particulate iron pools.
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Hierro , Minerales , Agua de Mar , Hierro/análisis , Hierro/química , Hierro/metabolismo , Ligandos , Minerales/análisis , Minerales/química , Minerales/metabolismo , Ciclo del Carbono , Conjuntos de Datos como Asunto , Océano Atlántico , Agua de Mar/análisis , Agua de Mar/química , Bermudas , Factores de Tiempo , Estaciones del Año , Soluciones/química , InternacionalidadRESUMEN
Gas exchange between the atmosphere and ocean interior profoundly impacts global climate and biogeochemistry. However, our understanding of the relevant physical processes remains limited by a scarcity of direct observations. Dissolved noble gases in the deep ocean are powerful tracers of physical air-sea interaction due to their chemical and biological inertness, yet their isotope ratios have remained underexplored. Here, we present high-precision noble gas isotope and elemental ratios from the deep North Atlantic (~32°N, 64°W) to evaluate gas exchange parameterizations using an ocean circulation model. The unprecedented precision of these data reveal deep-ocean undersaturation of heavy noble gases and isotopes resulting from cooling-driven air-to-sea gas transport associated with deep convection in the northern high latitudes. Our data also imply an underappreciated and large role for bubble-mediated gas exchange in the global air-sea transfer of sparingly soluble gases, including O2, N2, and SF6. Using noble gases to validate the physical representation of air-sea gas exchange in a model also provides a unique opportunity to distinguish physical from biogeochemical signals. As a case study, we compare dissolved N2/Ar measurements in the deep North Atlantic to physics-only model predictions, revealing excess N2 from benthic denitrification in older deep waters (below 2.9 km). These data indicate that the rate of fixed N removal in the deep Northeastern Atlantic is at least three times higher than the global deep-ocean mean, suggesting tight coupling with organic carbon export and raising potential future implications for the marine N cycle.
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The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly characterized. Current practice is guided through physician preference rather than established evidence. Identification of effective BT modalities and factors predictive of response could improve both CAR-T intention to treat and clinical outcomes. We assessed BT modality and response in 375 adult patients with LBCL in relation to outcomes after axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel (Tisa-cel) administration. The majority of patients received BT with chemotherapy (57%) or radiotherapy (17%). We observed that BT was safe for patients, with minimal morbidity or mortality. We showed that complete or partial response to BT conferred a 42% reduction in disease progression and death after CD19CAR-T therapy. Multivariate analysis identified several factors associated with likelihood of response to BT, including response to last line therapy, the absence of bulky disease, and the use of polatuzumab-containing chemotherapy regimens. Our data suggested that complete or partial response to BT may be more important for Tisa-cel than for Axi-cel, because all patients receiving Tisa-cel with less than partial response to BT experienced frank relapse within 12 months of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned toward optimal response and disease debulking, to improve patient outcomes associated with CD19CAR-T. Polatuzumab-containing regimens should be strongly considered for all suitable patients, and failure to achieve complete or partial response to BT before Tisa-cel administration may prompt consideration of further lines of BT where possible.
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Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Adulto , Humanos , Recurrencia Local de Neoplasia , Terapia Puente , Proteínas Adaptadoras Transductoras de Señales , Antígenos CD19/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológicoRESUMEN
Deep convective mixing of dissolved and suspended organic matter from the surface to depth can represent an important export pathway of the biological carbon pump. The seasonally oligotrophic Sargasso Sea experiences annual winter convective mixing to as deep as 300 m, providing a unique model system to examine dissolved organic matter (DOM) export and its subsequent compositional transformation by microbial oxidation. We analyzed biogeochemical and microbial parameters collected from the northwestern Sargasso Sea, including bulk dissolved organic carbon (DOC), total dissolved amino acids (TDAA), dissolved metabolites, bacterial abundance and production, and bacterial community structure, to assess the fate and compositional transformation of DOM by microbes on a seasonal time-scale in 2016-2017. DOM dynamics at the Bermuda Atlantic Time-series Study site followed a general annual trend of DOC accumulation in the surface during stratified periods followed by downward flux during winter convective mixing. Changes in the amino acid concentrations and compositions provide useful indices of diagenetic alteration of DOM. TDAA concentrations and degradation indices increased in the mesopelagic zone during mixing, indicating the export of a relatively less diagenetically altered (i.e., more labile) DOM. During periods of deep mixing, a unique subset of dissolved metabolites, such as amino acids, vitamins, and benzoic acids, was produced or lost. DOM export and compositional change were accompanied by mesopelagic bacterial growth and response of specific bacterial lineages in the SAR11, SAR202, and SAR86 clades, Acidimicrobiales, and Flavobacteria, during and shortly following deep mixing. Complementary DOM biogeochemistry and microbial measurements revealed seasonal changes in DOM composition and diagenetic state, highlighting microbial alteration of the quantity and quality of DOM in the ocean.
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Relapsed or refractory primary central nervous system lymphoma (rrPCNSL) confers a poor prognosis with no accepted standard of care. Very few prospective studies have been conducted in this patient group. This study was a multicenter phase 1/2 study that investigated thiotepa in combination with ifosfamide, etoposide, and rituximab (TIER) for the treatment of PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. A 3 + 3 design investigated the recommended phase 2 dose of thiotepa for a single-stage phase 2 cohort by assessing the activity of 2 cycles of TIER against rrPCNSL. The primary outcome was overall response rate. The dose-finding study demonstrated that 50 mg/m2 of thiotepa could be safely delivered within the TIER regimen. No dose-limiting toxicities were encountered in phase 1, and TIER was well-tolerated by the 27 patients treated in phase 2. The most common grade 3 to 4 toxicities were neutropenia (56% of patients) and thrombocytopenia (39%). An overall response was confirmed in 14 patients (52%), which met the prespecified threshold for clinically relevant activity. The median progression-free survival was 3 months (95% confidence interval [CI], 2 to 6 months) and overall survival 5 months (95% CI, 3 to 9 months). Exploratory analyses suggest a greater benefit for thiotepa-naïve patients. Six patients successfully completed autologous stem cell transplantation (ASCT) consolidation, with 4 experiencing durable remissions after a median follow-up of 50 months. The TIER regimen can be delivered safely and is active against rrPCNSL. When it is followed by ASCT, it can provide durable remission and long-term survival. However, for the majority of patients, prognosis remains poor, and novel treatment strategies are urgently needed. This trial was registered at https://www.clinicaltrialsregister.eu/ctr-search/search as EudraCT 2014-000227-24 and ISRCTN 12857473.
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Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Estudios Prospectivos , Tiotepa/uso terapéutico , Trasplante AutólogoRESUMEN
Vast and diverse microbial communities exist within the ocean. To better understand the global influence of these microorganisms on Earth's climate, we developed a robot capable of sampling dissolved and particulate seawater biochemistry across ocean basins while still capturing the fine-scale biogeochemical processes therein. Carbon and other nutrients are acquired and released by marine microorganisms as they build and break down organic matter. The scale of the ocean makes these processes globally relevant and, at the same time, challenging to fully characterize. Microbial community composition and ocean biochemistry vary across multiple physical scales up to that of the ocean basins. Other autonomous underwater vehicles are optimized for moving continuously and, primarily, horizontally through the ocean. In contrast, Clio, the robot that we describe, is designed to efficiently and precisely move vertically through the ocean, drift laterally in a Lagrangian manner to better observe water masses, and integrate with research vessel operations to map large horizontal scales to a depth of 6000 meters. We present results that show how Clio conducts high-resolution sensor surveys and sample return missions, including a mapping of 1144 kilometers of the Sargasso Sea to a depth of 1000 meters. We further show how the samples obtain filtered biomass from seawater that enable genomic and proteomic measurements not possible through in situ sensing. These results demonstrate a robotic oceanography approach for global-scale surveys of ocean biochemistry.
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BACKGROUND: Optimal upfront therapy for posttransplant lymphoproliferative disease (PTLD) arising after solid organ transplant remains contentious. Rituximab monotherapy (R-Mono) in unselected patients has shown a lack of durable remissions. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based chemotherapy confers improved response rates, although concerns exist about toxicity. METHODS: This multicenter retrospective study reports outcomes for adults with biopsy-proven B-cell PTLD treated initially with R-Mono or Rituximab plus CHOP (R-CHOP). Selection of therapy was made according to physician preference. RESULTS: Among 101 patients, 41 received R-Mono and 60 had R-CHOP. Most (93%) had undergone renal or liver transplantation. R-CHOP showed a trend toward improved complete (53% versus 71%; P = 0.066) and overall (75% versus 90%; P = 0.054) response rates. In the R-Mono group, 13 of 41 (32%) subsequently received chemotherapy, while 25 of 41 (61%) remained progression-free without further therapy. With median follow-up of 47 months, overall survival (OS) was similar for R-Mono and R-CHOP, with 3-year OS of 71% and 63%, respectively (P = 0.722). Non-PTLD mortality was 3 of 41 (7%) and 4 of 60 (7%) within 12 months of R-Mono or R-CHOP, respectively. The International Prognostic Index was statistically significant, with low- (0-2 points) and high-risk (≥3 points) groups exhibiting 3-year OS of 78% and 54%, respectively (P = 0.0003). In low-risk PTLD, outcomes were similar between therapies. However, in high-risk disease R-Mono conferred an inferior complete response rate (21% versus 68%; P = 0.006), albeit with no impact on survival. CONCLUSIONS: Our data support R-Mono as initial therapy for PTLD arising after renal or liver transplantation. However, upfront R-CHOP may benefit selected high-risk cases in whom rapid attainment of response is desirable.
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Antineoplásicos Inmunológicos/uso terapéutico , Trastornos Linfoproliferativos/tratamiento farmacológico , Trasplante de Órganos/efectos adversos , Rituximab/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Inglaterra , Femenino , Humanos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Trasplante de Órganos/mortalidad , Prednisona/uso terapéutico , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de Riesgo , Rituximab/efectos adversos , Factores de Tiempo , Vincristina/uso terapéutico , Adulto JovenRESUMEN
Outcome of patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) remains poor, highlighting the need for novel treatment approaches. The multicentre randomised phase II LEGEND trial evaluated lenalidomide in combination with rituximab, methylprednisolone and gemcitabine (R-GEM-L) vs. standard R-GEM-P as second-line treatment of DLBCL. The study closed early to recruitment after the planned interim analysis failed to demonstrate a complete response (CR) rate of ≥ 40% in either arm. Among 34 evaluable patients, 7/18 (38.9%) achieved CR with R-GEM-L and 3/16 (18.8%) with R-GEM-P. Median event-free and overall survival was 3.5/3.8 months and 10.8/8.3 months for R-GEM-L and R-GEM-P, respectively. The incidence of grade ≥ 3 toxicities was 52% in R-GEM-L and 83% in R-GEM-P. Efficacy and tolerability of R-GEM-L seem comparable with R-GEM-P and other standard salvage therapies, but a stringent design led to early trial closure. Combination of lenalidomide with gemcitabine-based regimens should be further evaluated in r/r DLBCL.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Rituximab/administración & dosificación , Rituximab/efectos adversos , Tasa de Supervivencia , GemcitabinaAsunto(s)
Alemtuzumab/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma de Células T/tratamiento farmacológico , Virosis/epidemiología , Adulto , Anciano , Alemtuzumab/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Humanos , Incidencia , Linfoma de Células T/inmunología , Linfoma de Células T/mortalidad , Dosis Máxima Tolerada , Persona de Mediana Edad , Prednisona/administración & dosificación , Prednisona/efectos adversos , Supervivencia sin Progresión , Tasa de Supervivencia , Vincristina/administración & dosificación , Vincristina/efectos adversos , Activación Viral/efectos de los fármacos , Activación Viral/inmunología , Virosis/inducido químicamente , Virosis/inmunologíaRESUMEN
The treatment landscape for mantle cell lymphoma (MCL) has changed dramatically in recent years, with findings from clinical trials reporting improvements in survival. Data on the general patient population are, however, sparse; and it is unclear whether the effects observed in clinical trials have translated into the real-world setting. To investigate this, we examined first-line and relapsed/refractory (RR) disease management in 335 MCL patients diagnosed between 2004 and 2015 in an established population-based patient cohort, along with data on demographic, diagnostic and prognostic factors. Marked treatment and survival changes were observed; first-line rituximab immunotherapy, for example, increased from 32% to 86% over the 11-year period, and median survival increased from 2·0 years among those first treated in 2004-2011 to 3·5 years among those treated in 2012-2015. Outcomes for RR disease also improved, from 8 months in 2004-2011 to 16·8 months in 2012-2015, coinciding with the introduction of agents, such as bendamustine and ibrutinib. Encouragingly, improvements were seen across all ages; 1-year overall survival among patients over 70 years treated for RR disease almost doubled. Our analyses underscore the importance of monitoring the impact of treatment changes in the real-world setting.
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Clorhidrato de Bendamustina/administración & dosificación , Inmunoterapia , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/terapia , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Rituximab/administración & dosificación , Adenina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperidinas , Tasa de Supervivencia , Reino Unido/epidemiologíaAsunto(s)
Cuidados a Largo Plazo/normas , Linfoma de Células B Grandes Difuso/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Pruebas Hematológicas , Humanos , Cuidados a Largo Plazo/métodos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Recurrencia , Inducción de Remisión , Adulto JovenRESUMEN
Modern reef-building corals sustain a wide range of ecosystem services because of their ability to build calcium carbonate reef systems. The influence of environmental variables on coral calcification rates has been extensively studied, but our understanding of their relative importance is limited by the absence of in situ observations and the ability to decouple the interactions between different properties. We show that temperature is the primary driver of coral colony (Porites astreoides and Diploria labyrinthiformis) and reef-scale calcification rates over a 2-year monitoring period from the Bermuda coral reef. On the basis of multimodel climate simulations (Coupled Model Intercomparison Project Phase 5) and assuming sufficient coral nutrition, our results suggest that P. astreoides and D. labyrinthiformis coral calcification rates in Bermuda could increase throughout the 21st century as a result of gradual warming predicted under a minimum CO2 emissions pathway [representative concentration pathway (RCP) 2.6] with positive 21st-century calcification rates potentially maintained under a reduced CO2 emissions pathway (RCP 4.5). These results highlight the potential benefits of rapid reductions in global anthropogenic CO2 emissions for 21st-century Bermuda coral reefs and the ecosystem services they provide.
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Antozoos/metabolismo , Calcificación Fisiológica , Arrecifes de Coral , Animales , Carbonato de Calcio/metabolismo , Dióxido de Carbono/química , Concentración de Iones de Hidrógeno , Luz , TemperaturaRESUMEN
The water vapour isotopic composition (1H216O, H218O and 1H2H16O) of the Atlantic marine boundary layer has been measured from 5 research vessels between 2012 and 2015. Using laser spectroscopy analysers, measurements have been carried out continuously on samples collected 10-20 meter above sea level. All the datasets have been carefully calibrated against the international VSMOW-SLAP scale following the same protocol to build a homogeneous dataset covering the Atlantic Ocean between 4°S to 63°N. In addition, standard meteorological variables have been measured continuously, including sea surface temperatures using calibrated Thermo-Salinograph for most cruises. All calibrated observations are provided with 15-minute resolution. We also provide 6-hourly data to allow easier comparisons with simulations from the isotope-enabled Global Circulation Models. In addition, backwards trajectories from the HYSPLIT model are supplied every 6-hours for the position of our measurements.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Linfadenopatía Inmunoblástica/tratamiento farmacológico , Linfoma de Células T/tratamiento farmacológico , Talidomida/administración & dosificación , Vidarabina/análogos & derivados , Anciano , Anciano de 80 o más Años , Ciclofosfamida/efectos adversos , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Linfadenopatía Inmunoblástica/mortalidad , Linfadenopatía Inmunoblástica/patología , Linfoma de Células T/mortalidad , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Talidomida/efectos adversos , Vidarabina/administración & dosificación , Vidarabina/efectos adversosRESUMEN
AIMS: We aimed to describe and compare survival in teenagers and young adults (TYAs) with cancer to that of younger children and older adults, to identify sub-populations at greater or lesser risk of death. METHODS: We compared survival in cancer patients diagnosed in the United Kingdom aged 13-24 years (TYAs) to those aged 0-12 (children) and 25-49 years (adults) using the National Cancer Data Repository. All cases had a first cancer diagnosis between 1st January 2001 and 31st December 2005 with censor date 31st December 2010 or death if earlier. RESULTS: We found six distinct statistically significant survival patterns. In pattern 1, the younger the age-group the better the 1- and 5-year survival (acute lymphoid leukaemia, carcinoma of ovary and melanoma). In pattern 2, TYAs had a worse 5-year survival than both children and young adults (bone and soft tissues sarcomas). In pattern 3, TYAs had a worse 1-year survival but no difference at 5-years (carcinoma of cervix and female breast). In pattern 4, TYAs had better 1-year survival than adults, but no difference at 5 years (carcinoma of liver and intrahepatic bile ducts, germ cell tumours of extra-gonadal sites). In pattern 5, the younger the age-group the better the 5-year survival, but the difference developed after 1-year (acute myeloid leukaemia, carcinoma of colon and rectum). In pattern 6, there was no difference in 1- and 5-year survival between TYAs and adults (testicular germ cell tumours, ovarian germ cell tumours and carcinoma of thyroid). CONCLUSION: TYAs with specific cancer diagnoses can be grouped according to 1- and 5-year survival patterns compared to children and young adults. To further improve survival for TYAs, age-specific biology, pharmacology, proteomics, genomics, clinician and patient behaviour studies embedded within clinical trials are required.