30 research outputs found
Nitrate- and silicate-competition among antarctic phytoplankton
Natural phytoplankton from antarctic waters in the Drake Passage were used for competition experiments in semicontinuous cultures. The outcome of interspecific competition for silicate and nitrate was studied at a range of Si:N ratios (from 2.6:1 to 425:1) and at three different dilution rates. For five species Monod kinetics of silicate-and nitrate-limited growth has been established. Comparison between theoretical predictions derived from Monod kinetics and the outcome of competition experiments showed only minor deviations. Contrary to literature data, considerable depletion of nitrate was found in antarctic seawater. Both the concentrations of soluble silicate and of nitrate were too low to support maximum growth rates of some of the diatom species under investigation
Durable response with single-agent acalabrutinib in patients with relapsed or refractory mantle cell lymphoma
Bruton tyrosine kinase (BTK) inhibitors have greatly
improved the spectrum of treatment options in mantle cell
lymphoma (MCL) [1–4]. Acalabrutinib is a highly selective,
orally administered, and potent BTK inhibitor with limited
off-target activity [5]. Acalabrutinib was approved in 2017
by the US Food and Drug Administration for the treatment
of relapsed/refractory MCL based on clinical data from the
open-label, multicenter, phase 2 ACE-LY-004 study of
acalabrutinib 100 mg twice daily [1]. Here, we present
updated results from the ACE-LY-004 study after a median
26-month follow-up.
Eligibility criteria and study design were published previously (Supplementary methods) [1]. Analysis of minimal
residual disease (MRD) was conducted after complete
response (CR) or partial response (PR) was achieved
using the quantitative ClonoSEQ next-generation sequencing (5 × 10−6
) assay (Adpative Biotechnologies, Seattle,
WA, USA) in consenting patients with available paired
archival tumor and whole blood samples. Data are updated
as of February 12, 2018
Human Tumour Immune Evasion via TGF-β Blocks NK Cell Activation but Not Survival Allowing Therapeutic Restoration of Anti-Tumour Activity
Immune evasion is now recognized as a key feature of cancer progression. In animal models, the activity of cytotoxic lymphocytes is suppressed in the tumour microenvironment by the immunosuppressive cytokine, Transforming Growth Factor (TGF)-β. Release from TGF-β-mediated inhibition restores anti-tumour immunity, suggesting a therapeutic strategy for human cancer. We demonstrate that human natural killer (NK) cells are inhibited in a TGF-β dependent manner following chronic contact-dependent interactions with tumour cells in vitro. In vivo, NK cell inhibition was localised to the human tumour microenvironment and primary ovarian tumours conferred TGF-β dependent inhibition upon autologous NK cells ex vivo. TGF-β antagonized the interleukin (IL)-15 induced proliferation and gene expression associated with NK cell activation, inhibiting the expression of both NK cell activation receptor molecules and components of the cytotoxic apparatus. Interleukin-15 also promotes NK cell survival and IL-15 excluded the pro-apoptotic transcription factor FOXO3 from the nucleus. However, this IL-15 mediated pathway was unaffected by TGF-β treatment, allowing NK cell survival. This suggested that NK cells in the tumour microenvironment might have their activity restored by TGF-β blockade and both anti-TGF-β antibodies and a small molecule inhibitor of TGF-β signalling restored the effector function of NK cells inhibited by autologous tumour cells. Thus, TGF-β blunts NK cell activation within the human tumour microenvironment but this evasion mechanism can be therapeutically targeted, boosting anti-tumour immunity
WHO global research priorities for antimicrobial resistance in human health
The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR
WHO global research priorities for antimicrobial resistance in human health
The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR
Impact de fertilisations a forte variabilite saisonniere et annuelle sur le phytoplancton d'un ecosysteme eutrophe
The fertilization of an eutrophic ecosystem of Western Europe (the Bay of Brest, 180 km super(2)) is observed from 1979 to 1982. Rich inputs in nutrients and dissolved organic matter flow into this semi-enclosed basin which waters are well mixed by the intensive action of tides. Natural and waste waters inputs are variable on a seasonal and annual scale; this induces large variations on the phytoplanktonic communities. This ecosystem presents high levels of primary production and low degree of maturity. By means of a model, the nitrate uptake by phytoplankton photosynthetic activity is simulated during spring 1980
Non-penetrating subclavian artery trauma: management by selective transluminally placed stent device
Non-penetrating injury to the subclavian artery has not often been reported. The limited experience of surgeons with this type of trauma and the difficult vascular control required for its management make it a surgical challenge. We report on two cases, one after blunt trauma and the other with a subclavian artery aneurysm following anterior dislocation of the shoulder. Percutaneous stent implantation in the subclavian artery was successfully performed with, in the second case, coil embolization of the aneurysm. Follow-up Doppler sonography and angiogram demonstrated patency and luminal integrity of the involved artery. This less invasive procedure may be a significant advance and a new approach in the conservative management of traumatic subclavian injury for selected cases
Variability in nutrient concentrations around Elephant Island, Antarctica, during 1991-1993
The nutrient status of the various water mass structures within a large sampling grid around Elephant Island are reported and the nutrient concentrations relative to jata from the physical and biological components of the Antarctic Marine Living Resources Programme are discussed. Concentrations of silicic acid, nitrate and phosphate (Si/N/P) were measured in the upper water column during January-March of three successive years. Samples were taken from eleven depths at 17 stations in 1991, and at four depths at 144 stations in 1992 and 182 stations in 1993. There was considerable variability in the concentrations of all three nutrients within the study area, but silicic acid showed the greatest variance among the water masses present in the sampling grid. The ratios (Si/N/P) of the nutrient deficits (difference in winter and summer values) in the upper 100 m differed considerably in Drake Passage waters as compared to Bransfield Strait waters, with both nitrate and silicic acid showing the greatest variance. Nutrient deficits did not increase from January to February, indicating that rates of replenishment of nutrients to the euphotic zone by physical processes and/or biological regeneration were approximately equal to the rate of uptake and assimilation by phytoplankton during that time period. The seasonal deficits, however, were substantial. Estimates of daily rates of primary production based on these nutrient deficits were comparable to the rates as measured by radiocarbon for Drake Passage waters, but much smaller for Bransfield Strait waters