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This state-of-the-art account unifies material developed in journal articles over the last 35 years, with two central thrusts: It describes a broad class of system models that the authors call 'stochastic processing networks' (SPNs), which include queueing networks and bandwidth sharing networks as prominent special cases; and in that context it explains and illustrates a method for stability analysis based on fluid models. The central mathematical result is a theorem that can be paraphrased as follows: If the fluid model derived from an SPN is stable, then the SPN itself is stable. Two topics discussed in detail are (a) the derivation of fluid models by means of fluid limit analysis, and (b) stability analysis for fluid models using Lyapunov functions. With regard to applications, there are chapters devoted to max-weight and back-pressure control, proportionally fair resource allocation, data center operations, and flow management in packet networks. Geared toward researchers and graduate students in engineering and applied mathematics, especially in electrical engineering and computer science, this compact text gives readers full command of the methods.
Our knowledge and understanding of the structure and function of complex host-associated communities has grown exponentially in the last decade through improvements in sequencing technologies. Despite this, there are still many outstanding research questions, which will undoubtably lead to many more. Concerted effort is required to elucidate the composition and function of taxonomic groups other than bacteria that constitute host microbiomes, and to extend our current cataloguing efforts to non-model and field-based host organisms. Further to this, we need to continue to move beyond the 'who?' question provided by relatively cheap amplicon sequencing to gain a better understanding of 'what?' the microbiome is doing, using metatranscriptomics approaches. Critically, we need to understand how members of the microbiome interact to confer function. Given the current unprecedented environmental change, microbiome plasticity may prove vital to host resilience and fitness. Furthermore, there is considerable potential for microbial biotechnology to improve numerous aspects of humanity, although care must be taken to ensure environmental and social justice prevail.
A classic example of microbiome function is its role in nutrient assimilation in both plants and animals, but other less obvious roles are becoming more apparent, particularly in terms of driving infectious and non-infectious disease outcomes and influencing host behaviour. However, numerous biotic and abiotic factors influence the composition of these communities, and host microbiomes can be susceptible to environmental change. How microbial communities will be altered by, and mitigate, the rapid environmental change we can expect in the next few decades remain to be seen. That said, given the enormous range of functional diversity conferred by microbes, there is currently something of a revolution in microbial bioengineering and biotechnology in order to address real-world problems including human and wildlife disease and crop and biofuel production. All of these concepts are explored in further detail throughout the book.
Through a long history of co-evolution, multicellular organisms form a complex of host cells plus many associated microorganism species. Consisting of algae, bacteria, archaea, fungi, protists and viruses, and collectively referred to as the microbiome, these microorganisms contribute to a range of important functions in their hosts, from nutrition, to behaviour and disease susceptibility. In this book, a diverse and international group of active researchers outline how multicellular organisms have become reliant on their microbiomes to function, and explore this vital interdependence across the breadth of soil, plant, animal and human hosts. They draw parallels and contrasts across hosts in different environments, and discuss how this invisible microbial ecosystem influences everything from the food we eat, to our health, to the correct functioning of ecosystems we depend on. This insightful read also pertinently encourages students and researchers in microbial ecology, ecology, and microbiology to consider how this interdependence may be key to mitigating environmental changes and developing microbial biotechnology to improve life on Earth.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
Technological advances have led to better patient outcomes and the expansion of clinical services in paediatric cardiology. This expansion creates an ever-growing workload for clinicians, which has led to workflow and staffing issues that need to be addressed. The objective of this study was the development of a novel tool to measure the clinical workload of a paediatric cardiology service in Cape Town, South Africa: The patient encounter index is a tool designed to quantify clinical workload. It is defined as a ratio of the measured duration of clinical work to the total time available for such work. This index was implemented as part of a prospective cross-sectional study design. Clinical workload data were collected over a 10-day period using time-and-motion sampling. Clinicians were contractually expected to spend 50% of their daily workload on patient care. The median patient encounter index for the Western Cape Paediatric Cardiac Service was 0.81 (range 0.19–1.09), reflecting that 81% of total contractual working time was spent on clinical activities. This study describes the development and implementation of a novel tool for clinical workload quantification and describes its application to a busy paediatric cardiology service in Cape Town, South Africa. This tool prospectively quantifies clinical workload which may directly influence patient outcomes. Implementation of this novel tool in the described setting clearly demonstrated the excessive workload of the clinical service and facilitated effective motivation for improved allocation of resources.
Rapeseed is a popular cover crop choice due to its deep-growing taproot, which creates soil macropores and increases water infiltration. Brassicaceae spp. that are mature or at later growth stages can be troublesome to control. Experiments were conducted in Delaware and Virginia to evaluate herbicides for terminating rapeseed cover crops. Two separate experiments, adjacent to each other, were established to evaluate rapeseed termination by 14 herbicide treatments at two timings. Termination timings included an early and late termination to simulate rapeseed termination prior to planting corn and soybean, respectively, for the region. At three locations where rapeseed height averaged 12 cm at early termination and 52 cm at late termination, glyphosate + 2,4-D was most effective, controlling rapeseed 96% 28 d after early termination (DAET). Paraquat + atrazine + mesotrione (92%), glyphosate + saflufenacil (91%), glyphosate + dicamba (91%), and glyphosate (86%) all provided at least 80% control 28 DAET. Rapeseed biomass followed a similar trend. Paraquat + 2,4-D (85%), glyphosate + 2,4-D (82%), and paraquat + atrazine + mesotrione (81%) were the only treatments that provided at least 80% control 28 d after late termination (DALT). Herbicide efficacy was less at Painter in 2017, where rapeseed height was 41 cm at early termination, and 107 cm at late termination. No herbicide treatments controlled rapeseed >80% 28 DAET or 28 DALT at this location. Herbicide termination of rapeseed is best when the plant is small; termination of large rapeseed plants may require mechanical of other methods beyond herbicides.
Residual herbicides are routinely applied to control troublesome weeds in pumpkin production. Fluridone and acetochlor, Groups 12 and 15 herbicides, respectively, provide broad-spectrum PRE weed control. Field research was conducted in Virginia and New Jersey to evaluate pumpkin tolerance and weed control to PRE herbicides. Treatments consisted of fomesafen at two rates, ethalfluralin, clomazone, halosulfuron, fluridone, S-metolachlor, acetochlor emulsifiable concentrate (EC), acetochlor microencapsulated (ME), and no herbicide. At one site, fluridone, acetochlor EC, acetochlor ME, and halosulfuron injured pumpkin 81%, 39%, 34%, and 35%, respectively, at 14 d after planting (DAP); crop injury at the second site was 40%, 8%, 19%, and 33%, respectively. Differences in injury between the two sites may have been due to the amount and timing of rainfall after herbicides were applied. Fluridone provided 91% control of ivyleaf morningglory and 100% control of common ragweed at 28 DAP. Acetochlor EC controlled redroot pigweed 100%. Pumpkin treated with S-metolachlor produced the most yield (10,764 fruits ha–1) despite broadcasting over the planted row; labeling requires a directed application to row-middles. A separate study specifically evaluated fluridone applied PRE at 42, 84, 126, 168, 252, 336, and 672 g ai ha–1. Fluridone resulted in pumpkin injury ≥95% when applied at rates of ≥168 g ai ha–1; significant yield loss was noted when the herbicide was applied at rates >42 g ai ha–1. We concluded that fluridone and acetochlor formulations are unacceptable candidates for pumpkin production.
Auxin herbicides are used in combinations to control glyphosate-resistant horseweed preplant burndown. Herbicide labels for 2,4-D–containing products require a 30-d rotation interval for planting cotton cultivars not resistant to 2,4-D. Dicamba labels require an accumulation of 2.5 cm of rain plus 21 d per 280 g ae ha–1 rotation interval for planting cotton cultivars not resistant to dicamba. Previous research has shown that cotton injury caused by dicamba applied 14 d before planting was transient with little effect on cotton yield, whereas 2,4-D has little effect on cotton when applied 7 d prior to planting. Injury caused by dicamba and 2,4-D is inversely related to rainfall received between herbicide application and cotton planting. Experiments were conducted to evaluate cotton tolerance to halauxifen-methyl, a new Group 4 herbicide, applied at intervals shorter than labeled requirements. Experiments were established near Painter and Suffolk, VA, and Belvidere, Clayton, Eure, Lewiston, and Rocky Mount, NC, during the 2017 and 2018 growing seasons. Herbicide treatments included halauxifen, dicamba, and 2,4-D applied 4, 3, 2, 1, and 0 wk before planting (WBP). Visible estimates of cotton growth reduction and total injury were collected 1, 2, and 4 wk after cotton emergence (WAE). Cotton stand and percentage of plants with distorted leaves were recorded 2 and 4 WAE. Cotton plant heights were recorded 4 and 8 WAE. Halauxifen was less injurious (9%) than dicamba (26%) or 2,4-D (21%) 2 WAE when herbicides were applied 0 WBP. Cotton stand reduction 2 WAE by halauxifen was less than 2,4-D and dicamba when applied 0 WBP. Injury observed from herbicides applied 1, 2, 3, and 4 WBP was minor, and no significant differences in cotton stand were observed. Early-season cotton injury was transient, and seed cotton yield was unaffected by any treatment.
Around 60 000 people in England live in mental health supported accommodation. There are three main types: residential care, supported housing and floating outreach. Supported housing and floating outreach aim to support service users in moving on to more independent accommodation within 2 years, but there has been little research investigating their effectiveness.
A 30-month prospective cohort study investigating outcomes for users of mental health supported accommodation.
We used random sampling, accounting for relevant geographical variation factors, to recruit 87 services (22 residential care, 35 supported housing and 30 floating outreach) and 619 service users (residential care 159, supported housing 251, floating outreach 209) across England. We contacted services every 3 months to investigate the proportion of service users who successfully moved on to more independent accommodation. Multilevel modelling was used to estimate how much of the outcome and cost variations were due to service type and quality, after accounting for service-user characteristics.
Overall 243/586 participants successfully moved on (residential care 15/146, supported housing 96/244, floating outreach 132/196). This was most likely for floating outreach service users (versus residential care: odds ratio 7.96, 95% CI 2.92–21.69, P < 0.001; versus supported housing: odds ratio 2.74, 95% CI 1.01–7.41, P < 0.001) and was associated with reduced costs of care and two aspects of service quality: promotion of human rights and recovery-based practice.
Most people do not move on from supported accommodation within the expected time frame. Greater focus on human rights and recovery-based practice may increase service effectiveness.
Leaf colour characteristics of 730 sweetpotato, Ipomoea batatas (L.) Lam. (Convolvulaceae), plant introduction (PI) accessions from the USDA sweetpotato germplasm collection were evaluated during 2012–2014. Colorimetry data for the abaxial and adaxial leaf surfaces were recorded using a tristimulus colorimeter and the CIE 1976 L*a*b* and CIE L*C*h* colour spaces. Most accessions (725 of 730 PIs) had dark-to-medium green leaves, but two PIs had totally purple leaves, and three PIs had yellow or yellow-green (chartreuse) leaves. For mature, field-grown green leaves, values for the red-green coordinate (a*) averaged −12.4 for the adaxial and −10.4 for the abaxial leaf surface. Values for the blue-yellow coordinate (b*) averaged 17.2 for the adaxial and 17.3 for the abaxial leaf surface. Hue angle (h*) for green leaves averaged 120.9° for the adaxial and 126.2° for the abaxial leaf surface. Colour saturation (Chroma, C*) averaged 21.3 for the adaxial and 20.2 for the abaxial leaf surface. Lightness (L*) averaged 35.4 for the adaxial and 47.2 for the abaxial leaf surface of green leaves. Late in the season, over one-half (53.9%) of the 730 PIs showed some level of purple pigmentation in the leaf lamina. Late-season purple leaves were collected and colour coordinates were recorded for 118 PIs grown in the field. For purple leaves, values for a*, b*, C*, L* and h* averaged 2.3, 6.2, 7.9, 28.2 and 64.4° for the adaxial surface and −1.0, 12.7, 13.9, 43.1 and 87.0° for the abaxial leaf surface, respectively.
OBJECTIVES/SPECIFIC AIMS: Inflammatory Bowel Disease (IBD) is a chronic, life-long condition characterized by inflammation of the intestine that greatly affects an individual’s quality of life. While biologic therapy directed against TNFα (anti-TNFα, Infliximab) and α4β7 integrin (anti-α4β7; Vedolizumab) is used to treat IBD, a substantial number of patients remain non-responsive. Using a comprehensive bioinformatics approach, the aim of this study was to characterize immune cell profiles and altered molecular pathways in IBD patient non-responders to anti-TNFα and anti-α4β7 therapy to determine potential mechanisms and/or indicators of treatment non-response. METHODS/STUDY POPULATION: Publicly available whole transcriptomes from 65 healthy control and IBD endoscopic biopsies were assessed (NCBI GEO GSE73661). Specifically, transcript profiles from responders or non-responders to anti-TNFα and anti-α4β7 therapy were utilized. Differentially expressed transcript profiles were obtained by comparing responders or non-responders prior to receiving therapy versus healthy controls using NCBI’s GEO2R after adjustment with Benjamini and Hochberg testing (p<0.05). Immune profiling of DEgs were analyzed by the core LM22 immune signature for subsets of B-, T-, dendritic-, mast-cells, macrophages, and neutrophils (CIBERSORT, cibersort.stanford.edu) (p<0.05). Networks, functional analysis, and interpretation of transcriptomic data were performed using Ingenuity Pathway Analysis (IPA) (Qiagen) (p<0.05). RESULTS/ANTICIPATED RESULTS: Initially, we determined colonic immune profiles in responders and non-responders to anti-TNFα and anti-α4β7 therapy. Compared to responders, in both anti-TNFα and anti-α4β7 non-responders we found elevated neutrophil levels (p<0.05). Specific to anti-TNFα treatment, non-responders demonstrated substantially reduced Treg cells (p<0.05); whereas, exclusive to anti-α4β7 treatment, non-responders showed elevated dendritic cells, activated CD4 T cells, and reduced M2 macrophages (p<0.05). Next we profiled differentially expressed transcripts to determine molecular pathways associated with therapy non-response. In both anti-TNFα and anti-α4β7 non-responders, we observed alterations in pathways specific to cellular growth and metabolism. Among cell growth pathways we found activated growth hormone, Wnt, ErB, and IGF-1 signaling; whereas, among metabolic regulation we found altered triglyceride, tryptophan, and leptin signaling. Moreover, unique to anti-TNFα non-responders, we found activated sphinogosine-1-phosphate and paxillin pathways. While non-response to anti-α4β7 indicated activation of SAPK/JNK and IL-9 signaling. DISCUSSION/SIGNIFICANCE OF IMPACT: Together these data define specific immune profiles and molecular pathways observed in non-responders to anti-TNFα and anti-α4β7 therapy. Our analysis identified substantial alterations in pathways specific to cellular growth and metabolism, identifying a link between non-response to biologic therapy and specific cell functions. These data suggest particular alterations in immune profiles and molecular pathways could play a role in non-response to biologic therapy, highlighting a future direction for personalized treatment regimens that could lead to more targeted use of existing therapies and more favorable patient health outcomes.
The infinitary propositional logic of here-and-there is important for the theory of answer set programming in view of its relation to strongly equivalent transformations of logic programs. We know a formal system axiomatizing this logic exists, but a proof in that system may include infinitely many formulas. In this note we describe a relationship between the validity of infinitary formulas in the logic of here-and-there and the provability of formulas in some finite deductive systems. This relationship allows us to use finite proofs to justify the validity of infinitary formulas.