Shallow lakes are hotspots for carbon processing and important natural sources of methane (CH4) emission. Ebullitive CH4 flux may constitute the overwhelming majority of total CH4 flux, but the ...episodic nature of ebullition events makes determining both quantity and the controlling factors challenging. Here we used the world's longest running shallow-lake mesocosm facility, where the experimental treatments are low and high nutrients crossed with three temperatures, to investigate the quantity and drivers of CH4 ebullition. The mean CH4 ebullition flux in the high nutrient treatment (41.5 ± 52.3 mg CH4–C m−2 d−1) mesocosms was significantly larger than in the low nutrient treatment (3.6 ± 5.4 mg CH4–C m−2 d−1) mesocosms, varying with temperature scenarios. Over eight weeks from June to August covered here warming resulted in a weak, but insignificant enhancement of CH4 ebullition. We found significant positive relationships between ebullition and chlorophyll-a, dissolved organic carbon (DOC), biodegradable DOC, δ2H, δ18O and δ13C-DOC, autochthonous dissolved organic matter (DOM) fluorescent components, and a fraction of lipids, proteins, and lignins revealed using ultrahigh-resolution mass spectrometry, and a negative relationship between ebullitive CH4 flux and the percentage volume inhabited of macrophytes. A 24 h laboratory bio-incubation experiment performed at room temperature (20 ± 2 °C) in the dark further revealed a rapid depletion of algal-DOM concurrent with a massive increased CH4 production, whereas soil-derived DOM had a limited effect on CH4 production. We conclude that eutrophication likely induced the loss of macrophytes and increase in algal biomass, and the resultant accumulation algal derived bio-labile DOM potentially drives enhanced outgassing of ebullitive CH4 from the shallow-lake mesocosms.
Display omitted
•CH4 ebullition enhanced with increasing Chl-a, DOC, BDOC and autochthonous DOM.•Highly biolabile protein-rich components are likely biodegraded from algal scums.•Autochthonous algal-derived DOC share enriched δ2H, δ18O and δ13C-DOC.•Markedly increased CH4 concurrent with rapid depletion of highly biolabile algal-DOM.
Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early ...initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure.
The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care.
DICTATE-AHF is a prospective, multicenter, open-label, randomized trial enrolling a planned 240 patients in the United States. Patients with type 2 diabetes hospitalized with hypervolemic AHF and an estimated glomerular filtration rate of at least 30 mL/min/1.73m2 are eligible for participation. Patients are randomly assigned 1:1 to dapagliflozin 10 mg once daily or structured usual care until day 5 or hospital discharge. Both treatment arms receive protocolized diuretic and insulin therapies. The primary endpoint is diuretic response expressed as the cumulative change in weight per cumulative loop diuretic dose in 40 mg intravenous furosemide equivalents. Secondary and exploratory endpoints include inpatient worsening AHF, 30-day hospital readmission for AHF or diabetic reasons, change in NT-proBNP, and measures of natriuresis. Safety endpoints include the incidence of hyper/hypoglycemia, ketoacidosis, worsening kidney function, hypovolemic hypotension, and inpatient mortality.
The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.
To update the ASCO clinical practice guideline on adjuvant endocrine therapy based on emerging data about the optimal duration of aromatase inhibitor (AI) treatment.
ASCO conducted a systematic ...review of randomized clinical trials from 2012 to 2018. Guideline recommendations were based on the Panel's review of the evidence from six trials.
The six included studies of AI treatment beyond 5 years of therapy demonstrated that extension of AI treatment was not associated with an overall survival advantage but was significantly associated with lower risks of breast cancer recurrence and contralateral breast cancer compared with placebo. Bone-related toxic effects were more common with extended AI treatment.
The Panel recommends that women with node-positive breast cancer receive extended therapy, including an AI, for up to a total of 10 years of adjuvant endocrine treatment. Many women with node-negative breast cancer should consider extended therapy for up to a total of 10 years of adjuvant endocrine treatment based on considerations of recurrence risk using established prognostic factors. The Panel noted that the benefits in absolute risk of reduction were modest and that, for lower-risk node-negative or limited node-positive cancers, an individualized approach to treatment duration that is based on considerations of risk reduction and tolerability was appropriate. A substantial portion of the benefit for extended adjuvant AI therapy was derived from prevention of second breast cancers. Shared decision making between clinicians and patients is appropriate for decisions about extended adjuvant endocrine treatment, including discussions about the absolute benefits in the reduction of breast cancer recurrence, the prevention of second breast cancers, and the impact of adverse effects of treatment. Additional information can be found at www.asco.org/breast-cancer-guidelines .
Fresh waters make a disproportionately large contribution to greenhouse gas (GHG) emissions, with shallow lakes being particular hot spots. Given their global prevalence, how GHG fluxes from shallow ...lakes are altered by climate change may have profound implications for the global carbon cycle. Empirical evidence for the temperature dependence of the processes controlling GHG production in natural systems is largely based on the correlation between seasonal temperature variation and seasonal change in GHG fluxes. However, ecosystem‐level GHG fluxes could be influenced by factors, which while varying seasonally with temperature are actually either indirectly related (e.g. primary producer biomass) or largely unrelated to temperature, for instance nutrient loading. Here, we present results from the longest running shallow‐lake mesocosm experiment which demonstrate that nutrient concentrations override temperature as a control of both the total and individual GHG flux. Furthermore, testing for temperature treatment effects at low and high nutrient levels separately showed only one, rather weak, positive effect of temperature (CH₄ flux at high nutrients). In contrast, at low nutrients, the CO₂ efflux was lower in the elevated temperature treatments, with no significant effect on CH₄ or N₂O fluxes. Further analysis identified possible indirect effects of temperature treatment. For example, at low nutrient levels, increased macrophyte abundance was associated with significantly reduced fluxes of both CH₄ and CO₂ for both total annual flux and monthly observation data. As macrophyte abundance was positively related to temperature treatment, this suggests the possibility of indirect temperature effects, via macrophyte abundance, on CH₄ and CO₂ flux. These findings indicate that fluxes of GHGs from shallow lakes may be controlled more by factors indirectly related to temperature, in this case nutrient concentration and the abundance of primary producers. Thus, at ecosystem scale, response to climate change may not follow predictions based on the temperature dependence of metabolic processes.
The siderophore aerobactin is the dominant siderophore produced by hypervirulent Klebsiella pneumoniae (hvKP) and was previously shown to be a major virulence factor in systemic infection. However, ...strains of hvKP commonly produce the additional siderophores yersiniabactin, salmochelin, and enterobactin. The roles of these siderophores in hvKP infection have not been optimally defined. To that end, site-specific gene disruptions were created in hvKP1 (wild type), resulting in the generation of hvKP1ΔiucA (aerobactin deficient), hvKP1ΔiroB (salmochelin deficient), hvKP1ΔentB (enterobactin and salmochelin deficient), hvKP1Δirp2 (yersiniabactin deficient), and hvKP1ΔentBΔirp2 (enterobactin, salmochelin, and yersiniabactin deficient). The growth/survival of these constructs was compared to that of their wild-type parent hvKP1 ex vivo in human ascites fluid, human serum, and human urine and in vivo in mouse systemic infection and pulmonary challenge models. Interestingly, in contrast to aerobactin, the inability to produce enterobactin, salmochelin, or yersiniabactin individually or in combination did not decrease the ex vivo growth/survival in human ascites or serum or decrease virulence in the in vivo infection models. Surprisingly, none of the siderophores increased growth in human urine. In human ascites fluid supplemented with exogenous siderophores, siderophores increased the growth of hvKP1ΔiucA, with the relative activity being enterobactin > aerobactin > yersiniabactin > salmochelin, suggesting that the contribution of aerobactin to virulence is dependent on both innate biologic activity and quantity produced. Taken together, these data confirm and extend a role for aerobactin as a critical virulence factor for hvKP. Since it appears that aerobactin production is a defining trait of hvKP strains, this factor is a potential antivirulence target.
To update the ASCO clinical practice guideline on adjuvant endocrine therapy on the basis of emerging data on the optimal duration of treatment, particularly adjuvant tamoxifen.
ASCO convened the ...Update Committee and conducted a systematic review of randomized clinical trials from January 2009 to June 2013 and analyzed three historical trials. Guideline recommendations were based on the Update Committee's review of the evidence. Outcomes of interest included survival, disease recurrence, and adverse events.
This guideline update reflects emerging data on duration of tamoxifen treatment. There have been five studies of tamoxifen treatment beyond 5 years of therapy. The two largest studies with longest reported follow-up show a breast cancer survival advantage with 10-year durations of tamoxifen use. In addition to modest gains in survival, extended therapy with tamoxifen for 10 years compared with 5 years was associated with lower risks of breast cancer recurrence and contralateral breast cancer.
Previous ASCO guidelines recommended treatment of women who have hormone receptor-positive breast cancer and are premenopausal with 5 years of tamoxifen, and those who are postmenopausal a minimum of 5 years of adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor (in sequence). If women are pre- or perimenopausal and have received 5 years of adjuvant tamoxifen, they should be offered 10 years total duration of tamoxifen. If women are postmenopausal and have received 5 years of adjuvant tamoxifen, they should be offered the choice of continuing tamoxifen or switching to an aromatase inhibitor for 10 years total adjuvant endocrine therapy.
Since its inception, the theory of alternative equilibria in shallow lakes has evolved and been applied to an ever wider range of ecological and socioecological systems. The theory posits the ...existence of two alternative stable states or equilibria, which in shallow lakes are characterised by either clear water with abundant plants or turbid water where phytoplankton dominate. Here, we used data simulations and real-world data sets from Denmark and north-eastern USA (902 lakes in total) to examine the relationship between shallow lake phytoplankton biomass (chlorophyll-a) and nutrient concentrations across a range of timescales. The data simulations demonstrated that three diagnostic tests could reliably identify the presence or absence of alternative equilibria. The real-world data accorded with data simulations where alternative equilibria were absent. Crucially, it was only as the temporal scale of observation increased (>3 years) that a predictable linear relationship between nutrient concentration and chlorophyll-a was evident. Thus, when a longer term perspective is taken, the notion of alternative equilibria is not required to explain the response of chlorophyll-a to nutrient enrichment which questions the utility of the theory for explaining shallow lake response to, and recovery from, eutrophication.
To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer.
A literature search identified ...relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations.
An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences.
The Update Committee recommends that postmenopausal women with hormone receptor-positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy.
With the implementation of the EU Water Framework Directive (WFD), the member states have to classify the ecological status of surface waters following standardised procedures. It was a matter of ...some surprise to lake ecologists that zooplankton were not included as a biological quality element (BQE) despite their being considered to be an important and integrated component of the pelagic food web. To the best of our knowledge, the decision of omitting zooplankton is not wise, and it has resulted in the withdrawal of zooplankton from many so-far-solid monitoring programmes. Using examples from particularly Danish, Estonian, and the UK lakes, we show that zooplankton (sampled from the water and the sediment) have a strong indicator value, which cannot be covered by sampling fish and phytoplankton without a very comprehensive and costly effort. When selecting the right metrics, zooplankton are cost-efficient indicators of the trophic state and ecological quality of lakes. Moreover, they are important indicators of the success/failure of measures taken to bring the lakes to at least good ecological status. Therefore, we strongly recommend the EU to include zooplankton as a central BQE in the WFD assessments, and undertake similar regional calibration exercises to obtain relevant and robust metrics also for zooplankton as is being done at present in the cases of fish, phytoplankton, macrophytes and benthic invertebrates.
To update the ASCO adjuvant endocrine therapy guideline based on emerging data concerning the benefits and risks of ovarian suppression in addition to standard adjuvant therapy in premenopausal women ...with estrogen receptor-positive breast cancer.
ASCO convened an Update Panel and conducted a systematic review of randomized clinical trials investigating ovarian suppression.
Two trials investigating the addition of ovarian suppression to tamoxifen did not show an overall clinical benefit for ovarian suppression. Nonetheless, the addition of ovarian suppression to standard adjuvant therapy with tamoxifen or with an aromatase inhibitor improved disease-free survival and improved freedom from breast cancer and distant recurrence compared with tamoxifen alone among the subset of patients who were at sufficient risk for recurrence such that adjuvant chemotherapy was warranted. Compared with tamoxifen alone, ovarian suppression was associated with a substantial increase in menopausal symptoms, sexual dysfunction, and diminished quality of life.
The Panel recommends that higher-risk patients should receive ovarian suppression in addition to adjuvant endocrine therapy, whereas lower-risk patients should not. Women with stage II or III breast cancers who would ordinarily be advised to receive adjuvant chemotherapy should receive ovarian suppression with endocrine therapy. The panel recommends that some women with stage I or II breast cancers at higher risk of recurrence who might consider chemotherapy may also be offered ovarian suppression with endocrine therapy. Women with stage I breast cancers not warranting chemotherapy should not receive ovarian suppression, nor should women with node-negative cancers 1 cm or less. Ovarian suppression may be administered with either tamoxifen or an aromatase inhibitor. Additional information is available at www.asco.org/guidelines/endocrinebreast and www.asco.org/guidelineswiki.
PDF
