Pro- and Antiinflammatory Cytokine Signaling: Reciprocal Antagonism Regulates Interferon-gamma Production by Human Natural Killer Cells

SummaryActivated monocytes produce proinflammatory cytokines (monokines) such as interleukin (IL)-12, IL-15, and IL-18 for induction of interferon-γ (IFN-γ) by natural killer (NK) cells. NK cells provide the antiinflammatory cytokine transforming growth factor (TGF)-β, an autocrine/negative regulator of IFN-γ. The ability of one signaling pathway to prevail over the other is likely important in controlling IFN-γ for the purposes of infection and autoimmunity, but the molecular mechanism(s) of how this counterregulation occurs is unknown. Here we show that in isolated human NK cells, proinflammatory monokines antagonize antiinflammatory TGF-β signaling by downregulating the expression of the TGF-β type II receptor, and its signaling intermediates SMAD2 and SMAD3. In contrast, TGF-β utilizes SMAD2, SMAD3, and SMAD4 to suppress IFN-γ and T-BET, a positive regulator of IFN-γ. Indeed, activated NK cells from Smad3−/− mice produce more IFN-γ in vivo than NK cells from wild-type mice. Collectively, our data suggest that pro- and antiinflammatory cytokine signaling reciprocally antagonize each other in an effort to prevail in the regulation of NK cell IFN-γ production

Mechanistic determination of fission product releases for a Mark III BWR plant

During the review of the GESSAR-II PRA by the Nuclear Regulatory Commission (NRC) and their contractors at Brookhaven National Laboratory (BNL) it was necessary to reanalyze potential fission product releases to the environment for several core meltdown accident sequences. The reanalysis was performed at BNL in two stages. The first stage was carried out prior to detailed mechanistic models were available at BNL and consisted of a sensitivity analysis using the MARCH and CORRAL computer codes. The effects of uncertainties in primary system retention, suppression pool scrubbing and core/concrete interactions on fission product release were handled by varying inputs to the MARCH/CORRAL codes. In this paper we outline the second stage of fission product release calculations, which was based on a system of codes developed under sponsorship of the Accident Source Term Program Office (ASTPO), USNRC. A comparison will be made between the range of source terms calculated by the first approach and the point estimate calculations provided by the more mechanistic codes. 8 refs., 2 tabs

Evaluation of containment failure modes and fission product releases during core meltdown accidents in a BWR with a Mark III containment

An assessment is described of potential failure modes and fission product releases for a large number of postulated core meltdown accidents in a BWR with a Mark III containment. For this containment design, the most important failure mode was found to be due to hydrogen related phenomena. A one-dimensional lumped parameter computer code has been developed and used to determine the probability of various hydrogen phenomena for a range of postulated core meltdown sequences. Potential containment loads have been estimated and compared against the containment capacity to determine the probability of containment failure. The fission product release assessment began by using the MARCH/CORRAL system of codes with key input parameters varied over a reasonable range. The parameters relate to primary system retention, re-emission, pool scrubbing, and fission product release in-vessel vs ex-vessel. The final step used more mechanistic calculations based on the system of codes recently developed under sponsorship of the Accident Source Term Program Office, NRC, and compares these predictions with the range of releases calculated in the sensitivity study

Landowner perceptions towards bioenergy production on degraded lands in Indonesia

Various tree species have been identified as having potential for bioenergy and restoration of degraded land. Using degraded land for bioenergy production provides Indonesia with an opportunity to meet its rapidly growing energy demand while creating productive landscapes. However, bioenergy production is not feasible without landowner participation. This study investigates factors affecting preferences for restoration tree species by analysing responses from 150 landowners with fire experience in Buntoi village in Central Kalimantan l. Results indicate 76% of landowners preferring familiar species with readily available markets, such as Albizia chinensis (sengon) and Hevea brasiliensis (rubber), for restoration on degraded land, with only 8% preferring Calophyllum inophyllum L. (nyamplung) for bioenergy production. The latter group of landowners revealed a capacity to handle the uncertainty of the bioenergy market as they had additional jobs and income, had migrated from Java where nyamplung is prevalent, or preferred agricultural extension to improve their technical capacity. These results contribute to identifying key conditions for a bottom-up approach to bioenergy production on degraded land in Indonesia: a stable bioenergy market for landowners, application of familiar bioenergy species, and agricultural extension support for capacity building

Rapid urbanisation in Singapore causes a shift from local provisioning and regulating to cultural ecosystem services use

Ecosystems support and enhance human life through providing ecosystem services. The use of ecosystem services changes over time, as environmental conditions and people's lifestyles change. Urbanisation is an extreme form of environmental change that can be expected to drastically alter the use of ecosystem services. We analysed people's childhood memories to quantify temporal changes in indicators of 11 ecosystem services in Singapore – a country which has rapidly urbanised over the past 70 years. We performed semi-structured interviews to elicit indicators of ecosystem service use from memories of childhood lifestyles and activities, comparing two groups of respondents; those born before 1960, and those born between 1989 and 1999. The two respondent groups recalled significantly different uses of ecosystem services, with a higher proportion of the pre-1960 respondents benefitting from locally-produced provisioning and regulating services, and a higher proportion of 1989–1999 respondents using most cultural services. This study thus demonstrates that urbanisation can decrease people's reliance on local ecosystems to provide raw materials, while leading to greater appreciation of cultural benefits. Management of ecosystem services in the present must consider the possibility that supply and demand of future ecosystem services may change in potentially unpredictable ways

Mapping degraded lands in Indonesia for bioenergy production potential

This study conducted a spatial analysis in Indonesia to estimate degraded lands potentially suitable for growing biodiesel species (Calophyllum inophyllum, Pongamia pinnata and Reutealis trisperma) and biomass species (Calliandra calothyrsus and Gliricidia sepium). Degraded lands have limited functions for food production, carbon storage, and conservation of biodiversity and native vegetation. Thus, identifying their potential to produce bioenergy can contribute to sustainable development by helping society to meet increasing energy demands and secure a new renewable energy source. The identified potential degraded lands were further examined with two scenarios: 1) an all-five-species scenario, examining the growth of all five species, and 2) a biodiesel-species-only scenario, analysing the growth of only biodiesel species. Study results illustrated approximately 3.5 million ha of degraded lands potentially suitable for these species in Indonesia. The all-five-species scenario indicated that these lands had the potential to produce 1,105 PJ yr¯¹ of biomass and 3 PJ yr¯¹ of biodiesel. The biodiesel-species-only scenario illustrated that these lands had the potential to produce 10 PJ yr¯¹ of biodiesel. In addition, many of these degraded lands were limited to support economies of scale for biofuel production due to their small land sizes. The study findings contribute to identifying lands with limited functions, modelling the growth of biofuel species on regional lands, and estimating carbon stocks of restored degraded lands in Indonesia

Emergency department antimicrobial use in a low-resource setting: results from a retrospective observational study at a referral hospital in Liberia

OBJECTIVE: Data on antimicrobial use in low-income and middle-income countries (LMICs) remain limited. In Liberia, the absence of local data impedes surveillance and may lead to suboptimal treatment, injudicious use and resistance against antimicrobials. This study aims to examine antimicrobial prescribing patterns for patients in the emergency department (ED) of a large Liberian public hospital. Secondarily, this prescribing was compared with WHO prescribing indicators. DESIGN: Retrospective observational study. SETTING: An adult ED of a large public hospital in Monrovia, Liberia. PARTICIPANTS: A total of 1082 adult patients (>18 years of age) were recorded in the ED, from 1 January to 30 June 2019. MAIN OUTCOME MEASURES: Number, type and name of antimicrobials ordered per patient were presented as number and percentages, with comparison to known WHO prescribing indicators. Pearson χ(2) tests were used to assess patient variables and trends in medication use. RESULTS: Of the total patients, 44.0% (n=476) were female and the mean age was 40.2 years (SD=17.4). An average of 2.78 (SD=2.02) medicines were prescribed per patient encounter. At least one antimicrobial was ordered for 64.5% encounters (n=713) and two or more antimicrobials for 35.7% (n=386). All antimicrobial orders in our sample used the generic name. Ceftriaxone, metronidazole and ampicillin were the most common and accounted for 61.2% (n=743) of antimicrobial prescriptions. The majority (99.9%, n=1211) of antimicrobials prescribed were from the WHO Essential Drugs List. CONCLUSION: This study is one of the first on ED-specific antimicrobial use in LMICs. We revealed a high rate of antimicrobial prescription, regardless of patient demographic or diagnosis. While empiric antimicrobial use is justified in certain acute clinical scenarios, the high rate from this setting warrants further investigation. The results of this study underscore the importance of ED surveillance to develop targeted antimicrobial stewardship interventions and improve patient care