Three-way fungal interactions affect the potential biological control of Himalayan balsam, Impatiens glandulifera

Himalayan balsam (Impatiens glandulifera) is one of the most invasive weeds across Europe. The rust fungus, Puccinia komarovii var. glanduliferae has been introduced as a biological control agent, but success has been patchy. Here, we investigated whether mycorrhizal and endophytic fungi can affect rust efficacy and plant growth. Over three experiments we found that AM fungi and the rust alone or together consistently reduced plant growth, but this depended on the identity of species in the AM inoculum. Meanwhile, AM fungi increased infection frequency of the endophyte Colletotrichum acutatum. Rust inoculation had no detrimental effects on mycorrhizal colonisation or C. acutatum infection, but the latter two fungi reduced rust sporulation. However, plant size was reduced when all three fungal types were present, suggesting that a combined fungal inoculum offers a promising approach for the control of this weed

From Random Matrices to Stochastic Operators

We propose that classical random matrix models are properly viewed as finite difference schemes for stochastic differential operators. Three particular stochastic operators commonly arise, each associated with a familiar class of local eigenvalue behavior. The stochastic Airy operator displays soft edge behavior, associated with the Airy kernel. The stochastic Bessel operator displays hard edge behavior, associated with the Bessel kernel. The article concludes with suggestions for a stochastic sine operator, which would display bulk behavior, associated with the sine kernel.Comment: 41 pages, 5 figures. Submitted to Journal of Statistical Physics. Changes in this revision: recomputed Monte Carlo simulations, added reference [19], fit into margins, performed minor editin

A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis

It was recently demonstrated that interleukin (IL)-23–driven IL-17–producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases. We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I–deficient (IL-1RI−/−) mice. Furthermore, the incidence of experimental autoimmune encephalomyelitis (EAE) was significantly lower in IL-1RI−/− compared with wild-type mice, and this correlated with a failure to induce autoantigen-specific ThIL-17 cells, whereas induction of Th1 and Th2 responses was not substantially different. However, EAE was induced in IL-1RI−/− mice by adoptive transfer of autoantigen-specific cells from wild-type mice with EAE. IL-23 alone did not induce IL-17 production by T cells from IL-1RI−/− mice, and IL-23–induced IL-17 production was substantially enhanced by IL-1α or IL-1β, even in the absence of T cell receptor stimulation. We demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor κB, and novel protein kinase C isoforms in IL-1– and IL-23–mediated IL-17 production. Tumor necrosis factor α also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent. Our findings demonstrate that IL-1 functions upstream of IL-17 to promote pathogenic ThIL-17 cells in EAE

Progress in Interferometry for LISA at JPL

Recent advances at JPL in experimentation and design for LISA interferometry include the demonstration of Time Delay Interferometry using electronically separated end stations, a new arm-locking design with improved gain and stability, and progress in flight readiness of digital and analog electronics for phase measurements.Comment: 11 pages, 9 figures, LISA 8 Symposium, Stanford University, 201

Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis in people with liver cirrhosis:a network meta-analysis

BACKGROUND:Approximately 2.5% of all hospitalisations in people with liver cirrhosis are for spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis is associated with significant short-term mortality; therefore, it is important to prevent spontaneous bacterial peritonitis in people at high risk of developing it. Antibiotic prophylaxis forms the mainstay preventive method, but this has to be balanced against the development of drug-resistant spontaneous bacterial peritonitis, which is difficult to treat, and other adverse events. Several different prophylactic antibiotic treatments are available; however, there is uncertainty surrounding their relative efficacy and optimal combination. OBJECTIVES:To compare the benefits and harms of different prophylactic antibiotic treatments for prevention of spontaneous bacterial peritonitis in people with liver cirrhosis using a network meta-analysis and to generate rankings of the different prophylactic antibiotic treatments according to their safety and efficacy. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to November 2018 to identify randomised clinical trials in people with cirrhosis at risk of developing spontaneous bacterial peritonitis. SELECTION CRITERIA:We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis undergoing prophylactic treatment to prevent spontaneous bacterial peritonitis. We excluded randomised clinical trials in which participants had previously undergone liver transplantation, or were receiving antibiotics for treatment of spontaneous bacterial peritonitis or other purposes. DATA COLLECTION AND ANALYSIS:We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS:We included 29 randomised clinical trials (3896 participants; nine antibiotic regimens (ciprofloxacin, neomycin, norfloxacin, norfloxacin plus neomycin, norfloxacin plus rifaximin, rifaximin, rufloxacin, sparfloxacin, sulfamethoxazole plus trimethoprim), and 'no active intervention' in the review. Twenty-three trials (2587 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, with or without other features of decompensation, having ascites with low protein or previous history of spontaneous bacterial peritonitis. The follow-up in the trials ranged from 1 to 12 months. Many of the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Overall, approximately 10% of trial participants developed spontaneous bacterial peritonitis and 15% of trial participants died. There was no evidence of differences between any of the antibiotics and no intervention in terms of mortality (very low certainty) or number of serious adverse events (very low certainty). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the trials reported health-related quality of life or the proportion of people with serious adverse events. There was no evidence of differences between any of the antibiotics and no intervention in terms of proportion of people with 'any adverse events' (very low certainty), liver transplantation (very low certainty), or the proportion of people who developed spontaneous bacterial peritonitis (very low certainty). The number of 'any' adverse events per participant was fewer with norfloxacin (rate ratio 0.74, 95% CrI 0.59 to 0.94; 4 trials, 546 participants; low certainty) and sulfamethoxazole plus trimethoprim (rate ratio 0.19, 95% CrI 0.02 to 0.81; 1 trial, 60 participants; low certainty) versus no active intervention. There was no evidence of differences between the other antibiotics and no intervention in the number of 'any' adverse events per participant (very low certainty). There were fewer other decompensation events with rifaximin versus no active intervention (rate ratio 0.61, 65% CrI 0.46 to 0.80; 3 trials, 575 participants; low certainty) and norfloxacin plus neomycin (rate ratio 0.06, 95% CrI 0.00 to 0.33; 1 trial, 22 participants; low certainty). There was no evidence of differences between the other antibiotics and no intervention in the number of decompensations events per participant (very low certainty). None of the trials reported health-related quality of life or development of symptomatic spontaneous bacterial peritonitis. One would expect some correlation between the above outcomes, with interventions demonstrating effectiveness across several outcomes. This was not the case. The possible reasons for this include sparse data and selective reporting bias, which makes the results unreliable. Therefore, one cannot draw any conclusions from these inconsistent differences based on sparse data. There was no evidence of any differences in the subgroup analyses (performed when possible) based on whether the prophylaxis was primary or secondary. FUNDING:the source of funding for five trials were organisations who would benefit from the results of the study; six trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 18 trials was unclear. AUTHORS' CONCLUSIONS:Based on very low-certainty evidence, there is considerable uncertainty about whether antibiotic prophylaxis is beneficial, and if beneficial, which antibiotic prophylaxis is most beneficial in people with cirrhosis and ascites with low protein or history of spontaneous bacterial peritonitis. Future randomised clinical trials should be adequately powered, employ blinding, avoid postrandomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, health-related quality of life, and decompensation events

Treatment for ascites in adults with decompensated liver cirrhosis:a network meta-analysis

BACKGROUND:Approximately 20% of people with cirrhosis develop ascites. Several different treatments are available; including, among others, paracentesis plus fluid replacement, transjugular intrahepatic portosystemic shunts, aldosterone antagonists, and loop diuretics. However, there is uncertainty surrounding their relative efficacy. OBJECTIVES:To compare the benefits and harms of different treatments for ascites in people with decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for ascites according to their safety and efficacy. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until May 2019 to identify randomised clinical trials in people with cirrhosis and ascites. SELECTION CRITERIA:We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and ascites. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS:We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS:We included a total of 49 randomised clinical trials (3521 participants) in the review. Forty-two trials (2870 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, without other features of decompensation, having mainly grade 3 (severe), recurrent, or refractory ascites. The follow-up in the trials ranged from 0.1 to 84 months. All the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Approximately 36.8% of participants who received paracentesis plus fluid replacement (reference group, the current standard treatment) died within 11 months. There was no evidence of differences in mortality, adverse events, or liver transplantation in people receiving different interventions compared to paracentesis plus fluid replacement (very low-certainty evidence). Resolution of ascites at maximal follow-up was higher with transjugular intrahepatic portosystemic shunt (HR 9.44; 95% CrI 1.93 to 62.68) and adding aldosterone antagonists to paracentesis plus fluid replacement (HR 30.63; 95% CrI 5.06 to 692.98) compared to paracentesis plus fluid replacement (very low-certainty evidence). Aldosterone antagonists plus loop diuretics had a higher rate of other decompensation events such as hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding compared to paracentesis plus fluid replacement (rate ratio 2.04; 95% CrI 1.37 to 3.10) (very low-certainty evidence). None of the trials using paracentesis plus fluid replacement reported health-related quality of life or symptomatic recovery from ascites. FUNDING:the source of funding for four trials were industries which would benefit from the results of the study; 24 trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 21 trials was unclear. AUTHORS' CONCLUSIONS:Based on very low-certainty evidence, there is considerable uncertainty about whether interventions for ascites in people with decompensated liver cirrhosis decrease mortality, adverse events, or liver transplantation compared to paracentesis plus fluid replacement in people with decompensated liver cirrhosis and ascites. Based on very low-certainty evidence, transjugular intrahepatic portosystemic shunt and adding aldosterone antagonists to paracentesis plus fluid replacement may increase the resolution of ascites compared to paracentesis plus fluid replacement. Based on very low-certainty evidence, aldosterone antagonists plus loop diuretics may increase the decompensation rate compared to paracentesis plus fluid replacement

Pathways to Coastal Resiliency: The Adaptive Gradients Framework

Current and future climate-related coastal impacts such as catastrophic and repetitive flooding, hurricane intensity, and sea level rise necessitate a new approach to developing and managing coastal infrastructure. Traditional “hard” or “grey” engineering solutions are proving both expensive and inflexible in the face of a rapidly changing coastal environment. Hybrid solutions that incorporate natural, nature-based, structural, and non-structural features may better achieve a broad set of goals such as ecological enhancement, long-term adaptation, and social benefits, but broad consideration and uptake of these approaches has been slow. One barrier to the widespread implementation of hybrid solutions is the lack of a relatively quick but holistic evaluation framework that places these broader environmental and societal goals on equal footing with the more traditional goal of exposure reduction. To respond to this need, the Adaptive Gradients Framework was developed and pilot-tested as a qualitative, flexible, and collaborative process guide for organizations to understand, evaluate, and potentially select more diverse kinds of infrastructural responses. These responses would ideally include natural, nature-based, and regulatory/cultural approaches, as well as hybrid designs combining multiple approaches. It enables rapid expert review of project designs based on eight metrics called “gradients”, which include exposure reduction, cost efficiency, institutional capacity, ecological enhancement, adaptation over time, greenhouse gas reduction, participatory process, and social benefits. The framework was conceptualized and developed in three phases: relevant factors and barriers were collected from practitioners and experts by survey; these factors were ranked by importance and used to develop the initial framework; several case studies were iteratively evaluated using this technique; and the framework was finalized for implementation. The article presents the framework and a pilot test of its application, along with resources that would enable wider application of the framework by practitioners and theorists

Transmission ecology of canine parvovirus in a multi-host, multi-pathogen system

Understanding multi-host pathogen maintenance and transmission dynamics is critical for disease control. However, transmission dynamics remain enigmatic largely because they are difficult to observe directly, particularly in wildlife. Here, we investigate the transmission dynamics of canine parvovirus (CPV) using state-space modelling of 20-years of CPV serology data from domestic dogs and African lions in the Serengeti ecosystem. We show that, although vaccination reduces the probability of infection in dogs, and despite indirect enhancement of population seropositivity as a result of vaccine shedding, the vaccination coverage achieved has been insufficient to prevent CPV from becoming widespread. CPV is maintained by the dog population and has become endemic with ~3.5-year cycles and prevalence reaching ~80%. While the estimated prevalence in lions is lower, peaks of infection consistently follow those in dogs. Dogs exposed to CPV are also more likely to become infected with a second multihost pathogen, canine distemper virus. However, vaccination can weaken this coupling raising questions about the value of monovalent versus polyvalent vaccines against these two pathogens. Our findings highlight the need to consider both pathogen- and host-level community interactions when seeking to understand the dynamics of multi-host pathogens and their implications for conservation, disease surveillance and control programmes

The NuSTAR ULX program

We present the results of the first large program of broadband ULX observations with NuSTAR, XMM-Newton and Suzaku, yielding high-quality spectra and timing measurements from 0.3-30 keV in 6 ULXs, providing powerful information for understanding the accretion modes and nature of the central BHs. In particular, we find that all ULXs in our sample have a clear cutoff above 10 keV. This cutoff is less pronounced than expected by Comptonization from a cold, thick corona. We confirm the presence of a soft excess at low energies in the brightest ULXs, with temperatures below ~ 0.5 keV. We make an estimates on the masses of several ULXs based on spectral variability and model fitting