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The first case of evolved protoporphyrinogen oxidase (PPO)-inhibitor resistance was observed in 2001 in common waterhemp [Amaranthus tuberculatus (Moq.) Sauer var. rudis (Sauer) Costea and Tardif]. This resistance in A. tuberculatus is most commonly conferred by deletion of the amino acid glycine at the 210th position (ΔGly-210) of the PPO enzyme (PPO2) encoded by PPX2. In a field in Kentucky in 2015, inadequate control of Amaranthus plants was observed following application of a PPO inhibitor. Morphological observations indicated that survivors included both A. tuberculatus and Palmer amaranth (Amaranthus palmeri S. Watson). Research was conducted to confirm species identities and resistance and then to determine whether resistance evolved independently in the two species or via hybridization. Results from a quantitative PCR assay based on the ribosomal internal transcribed spacer confirmed that both A. tuberculatus and A. palmeri coexisted in the field. The mutation conferring ΔGly-210 in PPO2 was identified in both species; phylogenetic analysis of a region of PPX2, however, indicated that the mutation evolved independently in the two species. Genotyping of greenhouse-grown plants that survived lactofen indicated that all A. tuberculatus survivors, but only a third of A. palmeri survivors, contained the ΔGly-210 mutation. Consequently, A. palmeri plants were evaluated for the presence of an arginine to glycine or methionine substitution at position 128 of PPO2 (Arg-128-Gly and Arg-128-Met). The Arg-128-Gly substitution was found to account for resistance that was not accounted for by the ΔGly-210 mutation in plants from the A. palmeri population. Results from this study provide a modern-day example of both parallel and convergent evolution occurring within a single field.
Introduction: The Prehospital Evidence-Based Practice (PEP) program is an online, freely accessible, continuously updated Emergency Medical Services (EMS) evidence repository. This summary describes the research evidence for the identification and management of adult patients suffering from sepsis syndrome or septic shock. Methods: PubMed was searched in a systematic manner. One author reviewed titles and abstracts for relevance and two authors appraised each study selected for inclusion. Primary outcomes were extracted. Studies were scored by trained appraisers on a three-point Level of Evidence (LOE) scale (based on study design and quality) and a three-point Direction of Evidence (DOE) scale (supportive, neutral, or opposing findings based on the studies’ primary outcome for each intervention). LOE and DOE of each intervention were plotted on an evidence matrix (DOE x LOE). Results: Eighty-eight studies were included for 15 interventions listed in PEP. The interventions with the most evidence were related to identification tools (ID) (n = 26, 30%) and early goal directed therapy (EGDT) (n = 21, 24%). ID tools included Systematic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA) and other unique measures. The most common primary outcomes were related to diagnosis (n = 30, 34%), mortality (n = 40, 45%) and treatment goals (e.g. time to antibiotic) (n = 14, 16%). The evidence rank for the supported interventions were: supportive-high quality (n = 1, 7%) for crystalloid infusion, supportive-moderate quality (n = 7, 47%) for identification tools, prenotification, point of care lactate, titrated oxygen, temperature monitoring, and supportive-low quality (n = 1, 7%) for vasopressors. The benefit of prehospital antibiotics and EGDT remain inconclusive with a neutral DOE. There is moderate level evidence opposing use of high flow oxygen. Conclusion: EMS sepsis interventions are informed primarily by moderate quality supportive evidence. Several standard treatments are well supported by moderate to high quality evidence, as are identification tools. However, some standard in-hospital therapies are not supported by evidence in the prehospital setting, such as antibiotics, and EGDT. Based on primary outcomes, no identification tool appears superior. This evidence analysis can guide selection of appropriate prehospital therapies.
Introduction: Early and accurate diagnosis of critical conditions is essential in emergency medical services (EMS). Serum lactate testing may be used to identify patients with worse prognosis, including sepsis. Recently, the use of a point-of-care lactate (POCL) test has been evaluated in guiding treatment in patients with sepsis. Operating as part of the Prehospital Evidence Based Practice (PEP) Program, the authors sought to identify and describe the body of evidence for POCL use in EMS and the emergency department (ED) for patients with sepsis. Methods: Following PEP methodology, in May 2018, PubMed was searched in a systematic manner. Title and abstract screening were conducted by the program coordinator. These studies were collected, appraised and added to the existing body of literature contained within the PEP database. Evidence appraisal was conducted by two reviewers who assigned both a level of evidence (LOE) on a novel three tier scale and a direction of evidence (supportive, neutral or opposing; based on primary outcome). Data on setting and study design were also extracted. Results: Eight studies were included in our analysis. Three of these studies were conducted in the ED setting; each investigating the POCL test's ability to predict severe sepsis, ICU admission or death. All three studies found supportive results for POCL. A systematic review on the use of POCL in the ED determined that this test can also improve time to treatment. Five of the total 8 studies were conducted prehospitally. Two of these studies were supportive of POCL use in the prehospital setting; in terms of feasibility and the ability to predict sepsis. Both of these study sites used this early information as part of initiating a “sepsis alert” pathway. The other three prehospital studies provide neutral support for POCL. One study demonstrated moderate ability of POCL to predict severe illness. Two studies found poor agreement between prehospital POCL and serum lactate values. Conclusion: Limited low and moderate quality evidence suggest POCL may be feasible and helpful in predicting sepsis in the prehospital setting. However, there is sparse and inconsistent support for specific important outcomes, including accuracy.
The strength of ceramics or glasses can be increased by placing their surfaces into compression. Techniques include ion exchange, temperature glazing, surface chemical reactions and stress-induced phase transformations. Although most of these techniques are well recognized, little effort has been expended In experimentally determining the magnitude of the compressive stress, and in particular, to use experimental evidence to identify important material and process parameters that need to be controlled. The goal of this investigation was to determine some of the factors that effect the magnitude, profile and depth of the compressive layer introduced by a structural phase transformation. X-ray residual stress measurements were used to directly determine the state of the surface residual stress.
OBJECTIVES/SPECIFIC AIMS: o To review the community’s recommendations on how to rebuild trust in the Flint community. o To review effective community engagement strategies utilized with the Flint Special Projects for project conceptualization, participant recruitment, data analysis, project oversight, and dissemination. METHODS/STUDY POPULATION: The study population includes nearly two hundred residents representing seniors, youth and diverse ethnicities recruited to participate in eleven focus group meetings. The population also represents the general public who attended informational meetings in Flint, Michigan to learn about the crisis and allow residents to voice their opinions and concerns during the onset of the crisis. The project is a mixed methods community based participatory research effort that utilized community decision making in all phases of the effort such as pre-conception, implementation, dissemination and advocacy to encourage the community’s recommendations are adopted at policy and institutional responsiveness levels. It includes three community engaged research efforts: (project 1) A qualitative analysis of community sentiment provided during 17 recorded legislative, media and community events, and (projects 2-3) two mixed methods efforts utilizing purposive sampling of stakeholders whose voice may not have been heard. RESULTS/ANTICIPATED RESULTS: The project presents a qualitative analysis of the community’s voice during the onset of the man-made disaster when the community first became aware of the emergency manager’s plans to switch the water source. It also reflects current perspectives of community voice since the projects are scheduled to end late February 2019. Findings from a trust measure administered to nearly two hundred residents will be presented, along with a qualitative analysis of focus group findings among segments of the population (seniors, youth, and diverse ethnicities) who may have been left out of narratives on the water crisis. Finally, the project will compare empowerment and resiliency approaches being utilized in Flint, Michigan to recover from the disaster with other approaches grounded in literature and theory. DISCUSSION/SIGNIFICANCE OF IMPACT: Communities of color often experience social determinants of health which negatively impact their health, well-being and human rights. Some Flint citizens are experiencing negative health consequences (i.e., rashes, brain and behavioral sequelle, fertility, etc.) as a result of the disaster, and are uncertain of health outcomes in the future. This is the first project to rigorously document and analyze levels of trust and mistrust in the city of Flint since the water disaster occurred. The qualitative research will guide future clinical research that will benefit this traumatized community experiencing high levels of mistrust (i.e., government, elected officials, etc.). The community engaged methodology involved residents and study participants in all phases of the project including project oversight, validating and analyzing data, and dissemination. This methodology will contribute to existing literature and theory on community based participatory research, community engaged research, team science and citizen science. The approaches empowered a call to action among residents, for example, seniors who attended two senior focus group sessions shared “they are hopeful and have a purpose,” resulting in the creation of a council (with officers) at their housing complex to advocate for the well-being of seniors during the recovery process. Recruitment methodologies were extremely successful due to resident level trust in community leaders and community partner organizations. Finally, the project’s examination of approaches encouraging empowerment and resiliency will provide lessons learned for other communities challenged with crisis.
Nutritional management of pigs to optimise growth demands pig-specific, time-specific and place-specific determination and provision of nutritional requirement. These elements need to be incorporated into response prediction models that operate in a real-time (not retrospective) closed-loop control environment. This implies appropriate means for the on-line measurement of response to change in nutrient provision, and the simultaneous means for manipulation of feeding level and feed quality. The paper describes how response prediction modelling and response measurement may now be achieved. Optimisation may be pursued with mixed objectives, including those of production efficiency and environmental protection.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Integrated management systems (IMS) for pigs offer the prospects of optimising meat production and minimising nitrogenous pollution through closed-loop control of pig growth by nutritional control (Whittemore, et al., 2001). Such an IMS requires a real-time sensor system, a nutritional model which is optimised in response to data collected in by the sensor system, and a control system which uses forward predictions of the model to predict the nutritional regime required to satisfy growth and pollution targets. An experiment was carried out to determine the accuracy to which a novel IMS system can direct pig weight gain and fatness towards preset targets through nutritional control.
The purpose of an integrated management system is to optimise both pig performance and environmental protection. A major impediment to this process has been the inability to measure and control the production process in real time, for specific and contemporary pig batches. Optimisation thus requires in-line measurement of pig growth performance, together with the means to change performance with adjustments to feed quantity and quality. This report deals with the use of visual image analysis (VIA) to provide the first of these; measurement of growth. VIA determines, continuously and in-line, the size and shape of the plan view of the pig as it stands at the feeder. Three seminal questions are here addressed. (i) can VIA be used to provide a reliable measure of pig weight, and (ii) how many days are required to elapse before a change in size can be reliably determined and how does the VIA system compare with daily weighing by a conventional weigh-scale, and (iii) can VIA sort pigs according to their shape?
The Molonglo Observatory Synthesis Telescope (MOST) is an 18000 m2 radio telescope located 40 km from Canberra, Australia. Its operating band (820–851 MHz) is partly allocated to telecommunications, making radio astronomy challenging. We describe how the deployment of new digital receivers, Field Programmable Gate Array-based filterbanks, and server-class computers equipped with 43 Graphics Processing Units, has transformed the telescope into a versatile new instrument (UTMOST) for studying the radio sky on millisecond timescales. UTMOST has 10 times the bandwidth and double the field of view compared to the MOST, and voltage record and playback capability has facilitated rapid implementaton of many new observing modes, most of which operate commensally. UTMOST can simultaneously excise interference, make maps, coherently dedisperse pulsars, and perform real-time searches of coherent fan-beams for dispersed single pulses. UTMOST operates as a robotic facility, deciding how to efficiently target pulsars and how long to stay on source via real-time pulsar folding, while searching for single pulse events. Regular timing of over 300 pulsars has yielded seven pulsar glitches and three Fast Radio Bursts during commissioning. UTMOST demonstrates that if sufficient signal processing is applied to voltage streams, innovative science remains possible even in hostile radio frequency environments.
Healthy adults (n 30) participated in a placebo-controlled, randomised, double-blinded, cross-over study consisting of two 28 d treatments (β2-1 fructan or maltodextrin; 3×5 g/d) separated by a 14-d washout. Subjects provided 1 d faecal collections at days 0 and 28 of each treatment. The ability of faecal bacteria to metabolise β2-1 fructan was common; eighty-seven species (thirty genera, and four phyla) were isolated using anaerobic medium containing β2-1 fructan as the sole carbohydrate source. β2-1 fructan altered the faecal community as determined through analysis of terminal restriction fragment length polymorphisms and 16S rRNA genes. Supplementation with β2-1 fructan reduced faecal community richness, and two patterns of community change were observed. In most subjects, β2-1 fructan reduced the content of phylotypes aligning within the Bacteroides, whereas increasing those aligning within bifidobacteria, Faecalibacterium and the family Lachnospiraceae. In the remaining subjects, supplementation increased the abundance of Bacteroidetes and to a lesser extent bifidobacteria, accompanied by decreases within the Faecalibacterium and family Lachnospiraceae. β2-1 Fructan had no impact on the metagenome or glycoside hydrolase profiles in faeces from four subjects. Few relationships were found between the faecal bacterial community and various host parameters; Bacteroidetes content correlated with faecal propionate, subjects whose faecal community contained higher Bacteroidetes produced more caproic acid independent of treatment, and subjects having lower faecal Bacteroidetes exhibited increased concentrations of serum lipopolysaccharide and lipopolysaccharide binding protein independent of treatment. We found no evidence to support a defined health benefit for the use of β2-1 fructans in healthy subjects.
The class of radio transients called Fast Radio Bursts (FRBs) encompasses enigmatic single pulses, each unique in its own way, hindering a consensus for their origin. The key to demystifying FRBs lies in discovering many of them in order to identity commonalities – and in real time, in order to find potential counterparts at other wavelengths. The recently upgraded UTMOST in Australia, is undergoing a backend transformation to rise as a fast transient detection machine. The first interferometric detections of FRBs with UTMOST, place their origin beyond the near-field region of the telescope thus ruling out local sources of interference as a possible origin. We have localised these bursts to much better than the ones discovered at the Parkes radio telescope and have plans to upgrade UTMOST to be capable of much better localisation still.
Predicting recurrent Clostridium difficile infection (rCDI) remains difficult. METHODS. We employed a retrospective cohort design. Granular electronic medical record (EMR) data had been collected from patients hospitalized at 21 Kaiser Permanente Northern California hospitals. The derivation dataset (2007–2013) included data from 9,386 patients who experienced incident CDI (iCDI) and 1,311 who experienced their first CDI recurrences (rCDI). The validation dataset (2014) included data from 1,865 patients who experienced incident CDI and 144 who experienced rCDI. Using multiple techniques, including machine learning, we evaluated more than 150 potential predictors. Our final analyses evaluated 3 models with varying degrees of complexity and 1 previously published model.
Despite having a large multicenter cohort and access to granular EMR data (eg, vital signs, and laboratory test results), none of the models discriminated well (c statistics, 0.591–0.605), had good calibration, or had good explanatory power.
Our ability to predict rCDI remains limited. Given currently available EMR technology, improvements in prediction will require incorporating new variables because currently available data elements lack adequate explanatory power.
This paper presents latest thinking from the Institute and Faculty of Actuaries’ Model Risk Working Party and follows on from their Phase I work, Model Risk: Daring to Open the Black Box. This is a more practical paper and presents the contributors’ experiences of model risk gained from a wide range of financial and non-financial organisations with suggestions for good practice and proven methods to reduce model risk. After a recap of the Phase I work, examples of model risk communication are given covering communication: to the Board; to the regulator; and to external stakeholders. We present a practical framework for model risk management and quantification with examples of the key actors, processes and cultural challenge. Lessons learned are then presented from other industries that make extensive use of models and include the weather forecasting, software and aerospace industries. Finally, a series of case studies in practical model risk management and mitigation are presented from the contributors’ own experiences covering primarily financial services.
This study aimed to determine prevalence of Ralstonia spp. in cystic fibrosis patients, look for any evidence of cross infection and to describe clinical outcomes for patients infected by Ralstonia spp. Prevalence of Ralstonia spp. was calculated annually from 2008 to 2016. Pulsed-field gel electrophoresis was performed on ⩾1 sample from patients with an isolation of Ralstonia spp. between 2008 and 2016. A prospective, longitudinal observational study of adult patients was performed with 12 months follow-up from recruitment. Prevalence of Ralstonia spp. rose from 0·6% in 2008 to 2·4% in 2016. In total 12 out of 14 (86%) patients with ⩾1 isolation of Ralstonia spp. developed chronic infection. A pair and a group of three unrelated patients with epidemiological connections shared strains of Ralstonia mannitolilytica. Lung function of Ralstonia spp. infected patients was moderately to severely impaired. Prevalence of Ralstonia spp. is low but increasing. The risk of a patient developing chronic Ralstonia spp. infection following first acquisition is high and cross-infection may be possible. Whether Ralstonia spp. infection causes increased pulmonary exacerbation frequency and lung function decline needs to be evaluated in larger prospective studies.
We are acquiring a large-area sample of faint, high-latitude carbon star candidates for the study of halo dynamics by using an intermediate-band color system with CCDs in efficient survey modes. Except for one odd dwarf carbon (C) star, G77-61, it has long been assumed that these faint C stars are distant giants. However, we recently demonstrated that three more faint C stars are high proper motion objects, and therefore dwarfs. Now we are completing a proper motion survey of known faint high-latitude C stars to search for additional C dwarfs. The CCD and proper motion surveys together will place significant limits on the space density of C stars, be they dwarfs or giants.
Six radio telescopes were operated as the first southern hemisphere VLBI array in April and May 1982. Observations were made at 2.3 and 8.4 Ghz. This array produced VLBI images of 28 southern hemisphere radio sources, high accuracy VLBI geodesy between southern hemisphere sites, and subarcsecond radio astrometry of celestial sources south of declination −45 degrees. This paper discusses only the astrophysical aspects of the experiment.
Mycobacterium marinum, a bacterium found in freshwater and saltwater, can infect persons with direct exposure to fish or aquariums. During December 2013, the New York City Department of Health and Mental Hygiene learned of four suspected or confirmed M. marinum skin or soft tissue infections (SSTIs) among persons who purchased whole fish from Chinese markets. Ninety-eight case-patients with non-tuberculous mycobacteria (NTM) SSTIs were identified with onset June 2013–March 2014. Of these, 77 (79%) were female. The median age was 62 years (range 30–91). Whole genome sequencing of clinical isolates revealed two main clusters and marked genetic diversity. Environmental samples from distributors yielded NTM though not M. marinum. We compared 56 case-patients with 185 control subjects who shopped in Chinese markets, frequency-matched by age group and sex. Risk factors for infection included skin injury to the finger or hand (odds ratio [OR]: 15·5; 95% confidence interval [CI]: 6·9–37·3), hand injury while preparing fish or seafood (OR 8·3; 95% CI 3·8–19·1), and purchasing tilapia (OR 3·6; 95% CI 1·1–13·9) or whiting (OR 2·7; 95% CI 1·1–6·6). A definitive environmental outbreak source was not identified.