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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.
Early detection and intervention strategies in patients at clinical high-risk (CHR) for syndromal psychosis have the potential to contain the morbidity of schizophrenia and similar conditions. However, research criteria that have relied on severity and number of positive symptoms are limited in their specificity and risk high false-positive rates. Our objective was to examine the degree to which measures of recency of onset or intensification of positive symptoms [a.k.a., new or worsening (NOW) symptoms] contribute to predictive capacity.
We recruited 109 help-seeking individuals whose symptoms met criteria for the Progression Subtype of the Attenuated Positive Symptom Psychosis-Risk Syndrome defined by the Structured Interview for Psychosis-Risk Syndromes and followed every three months for two years or onset of syndromal psychosis.
Forty-one (40.6%) of 101 participants meeting CHR criteria developed a syndromal psychotic disorder [mostly (80.5%) schizophrenia] with half converting within 142 days (interquartile range: 69–410 days). Patients with more NOW symptoms were more likely to convert (converters: 3.63 ± 0.89; non-converters: 2.90 ± 1.27; p = 0.001). Patients with stable attenuated positive symptoms were less likely to convert than those with NOW symptoms. New, but not worsening, symptoms, in isolation, also predicted conversion.
Results suggest that the severity and number of attenuated positive symptoms are less predictive of conversion to syndromal psychosis than the timing of their emergence and intensification. These findings also suggest that the earliest phase of psychotic illness involves a rapid, dynamic process, beginning before the syndromal first episode, with potentially substantial implications for CHR research and understanding the neurobiology of psychosis.
Myocardial strain measurements are increasingly used to detect complications following heart transplantation. However, the temporal association of these changes with allograft rejection is not well defined. The aim of this study was to describe the evolution of strain measurements prior to the diagnosis of rejection in paediatric heart transplant recipients.
All paediatric heart transplant recipients (2004–2015) with at least one episode of acute rejection were identified. Longitudinal and circumferential strain measurements were assessed at the time of rejection and retrospectively on all echocardiograms until the most recent negative biopsy. Smoothing technique (LOESS) was used to visualise the changes of each variable over time and estimate the time preceding rejection at which alterations are first detectable.
A total of 58 rejection episodes were included from 37 unique patients. In the presence of rejection, there were decrements from baseline in global longitudinal strain (−18.2 versus −14.1), global circumferential strain (−24.1 versus −19.6), longitudinal strain rate (−1 versus −0.8), circumferential strain rate (−1.3 versus −1.1), peak longitudinal early diastolic strain rate (1.3 versus 1), and peak circumferential early diastolic strain rate (1.5 versus 1.3) (p<0.01 for all). The earliest detectable changes occurred 45 days prior to rejection with simultaneous alterations in myocardial strain and ejection fraction.
Changes in graft function can be detected non-invasively prior to the diagnosis of rejection. However, changes in strain occur concurrently with a decline in ejection fraction. Strain measurements aid in the non-invasive detection of rejection, but may not facilitate earlier diagnosis compared to more traditional measures of ventricular function.
The widespread use of herbicides in cropping systems has led to the evolution of resistance in major weeds. The resultant loss of herbicide efficacy is compounded by a lack of new herbicide sites of action, driving demand for alternative weed control technologies. While there are many alternative methods for control, identifying the most appropriate method to pursue for commercial development has been hampered by the inability to compare techniques in a fair and equitable manner. Given that all currently available and alternative weed control methods share an intrinsic energy consumption, the aim of this review was to compare methods based on energy consumption. Energy consumption was compared for chemical, mechanical, and thermal weed control technologies when applied as broadcast (whole-field) and site-specific treatments. Tillage systems, such as flex-tine harrow (4.2 to 5.5 MJ ha−1), sweep cultivator (13 to 14 MJ ha−1), and rotary hoe (12 to 17 MJ ha−1) consumed the least energy of broadcast weed control treatments. Thermal-based approaches, including flaming (1,008 to 4,334 MJ ha−1) and infrared (2,000 to 3,887 MJ ha−1), are more appropriate for use in conservation cropping systems; however, their energy requirements are 100- to 1,000-fold greater than those of tillage treatments. The site-specific application of weed control treatments to control 2-leaf-stage broadleaf weeds at a density of 5 plants m−2 reduced energy consumption of herbicidal, thermal, and mechanical treatments by 97%, 99%, and 97%, respectively. Significantly, this site-specific approach resulted in similar energy requirements for current and alternative technologies (e.g., electrocution [15 to 19 MJ ha−1], laser pyrolysis [15 to 249 MJ ha−1], hoeing [17 MJ ha−1], and herbicides [15 MJ ha−1]). Using similar energy sources, a standardized energy comparison provides an opportunity for estimation of weed control costs, suggesting site-specific weed management is critical in the economically realistic implementation of alternative technologies.
Late-life depression has become an important public health problem. Available evidence suggests that late-life depression is associated with all-cause and cardiovascular mortality among older adults living in the community, although the associations have not been comprehensively reviewed and quantified.
To estimate the pooled association of late-life depression with all-cause and cardiovascular mortality among community-dwelling older adults.
We conducted a systematic review and meta-analysis of prospective cohort studies that examine the associations of late-life depression with all-cause and cardiovascular mortality in community settings.
A total of 61 prospective cohort studies from 53 cohorts with 198 589 participants were included in the systematic review and meta-analysis. A total of 49 cohorts reported all-cause mortality and 15 cohorts reported cardiovascular mortality. Late-life depression was associated with increased risk of all-cause (risk ratio 1.34; 95% CI 1.27, 1.42) and cardiovascular mortality (risk ratio 1.31; 95% CI 1.20, 1.43). There was heterogeneity in results across studies and the magnitude of associations differed by age, gender, study location, follow-up duration and methods used to assess depression. The associations existed in different subgroups by age, gender, regions of studies, follow-up periods and assessment methods of late-life depression.
Late-life depression is associated with higher risk of both all-cause and cardiovascular mortality among community-dwelling elderly people. Future studies need to test the effectiveness of preventing depression among older adults as a way of reducing mortality in this population. Optimal treatment of late-life depression and its impact on mortality require further investigation.
In north-central China, subsistence practices transitioned from hunting and gathering to millet-based agriculture between the early and middle Holocene. To better understand how ancient environmental changes influenced this shift in subsistence strategies and human activities at regional to local levels, we conducted palynological and lithologic analyses on radiocarbon-dated sediment cores from the Luoyang Basin, western Henan Province. Our palynological results suggest that vegetation shifted from broad-leaved deciduous forest (9230–8850 cal yr BP) to steppe-meadow vegetation (8850–7550 cal yr BP), and then to steppe with sparse trees (7550–6920 cal yr BP). Lithologic analyses also indicate that the stabilization of the Luoyang Basin’s floodplain after ~8370 cal yr BP might have attracted people to move into the basin, promoting the emergence of millet-based agriculture during the Peiligang culture period (8500–7000 cal yr BP). Once agricultural practices emerged, the climatic optimum after ~7550 cal yr BP likely facilitated the expansion of the Yangshao culture (7000–5000 cal yr BP) in north-central China. As agriculture intensified, pollen taxa related to human disturbance, such as Urtica, increased in abundance.
OBJECTIVES/SPECIFIC AIMS: Recent data suggest that fecal microbiota and intraluminal organic acids may play an important role in irritable bowel syndrome (IBS) pathogenesis through effects on intestinal secretion and motility. Understanding their contribution will be critical in developing diagnostic and treatment strategies. Objectives and goals of this study will be to: (1) compare fecal microbiota and fecal organic acids in IBS patients and controls and (2) investigate the association between colonic transit and fecal microbiota in IBS patients and controls. METHODS/STUDY POPULATION: We propose a prospective investigation of fecal organic acids, colonic transit and fecal microbiota in 36 IBS patients and 18 healthy controls. The target population will be adults ages 18–65 years meeting Rome IV criteria for IBS (both diarrhea predominant and constipation-predominant, IBS-D, and IBS-C) and asymptomatic controls. Exclusion criteria are: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, liver disease, or elevated AST/ALT>2.0x the upper limit of normal, (b) prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy>6 months before study initiation, (c) ingestion of prescription, over the counter, or herbal medications affecting gastrointestinal transit or study interpretation within 6 months of study initiation for controls or within 2 days before study initiation for IBS patients, (d) pregnant females, (e) antibiotic usage within 3 months prior to study participation, (f) prebiotic or probiotic usage within the 2 weeks prior to study initiation, (g) tobacco users. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid (SCFA) excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100-g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis and frozen. Frozen aliquots will be shipped to the Metabolite Profiling Facility at Purdue University and the Mayo Clinic Department of Laboratory Medicine and Pathology for SCFA and bile acid measurements, respectively. Analysis of fecal microbiota will be performed in the research laboratory of Dr. David Nelson in collaboration with bioinformatics expertise affiliated with the Nelson lab. Colonic transit time will be measured with the previously validated method using radio-opaque markers. Generalized linear models will be used as the analysis framework for comparing study endpoints among groups. RESULTS/ANTICIPATED RESULTS: This study seeks to examine the innovative concept that specific microbial signatures are associated with increased fecal excretion of organic acids to provide unique insights on a potential mechanistic link between altered intraluminal organic acids and fecal microbiota. DISCUSSION/SIGNIFICANCE OF IMPACT: Results may lead to development of targets for novel therapies and diagnostic biomarkers for IBS, emphasizing the role of the fecal metabolome.
We consider a resource allocation model to analyze investment strategies for financial services firms in order to minimize their operational risk losses. A firm has to decide how much to invest in human resources and in infrastructure (information technology). The operational risk losses are a function of the activity level of the firm, of the amounts invested in personnel and in infrastructure, and of interaction effects between the amounts invested in personnel and infrastructure. We first consider a deterministic setting and show certain monotonicity properties of the optimal investments assuming general loss functions that are convex. We find that because of the interaction effects “economies of scale" may not hold in our setting, in contrast to a typical manufacturing environment. We then consider a general polynomial loss function in a stochastic setting with the number of transactions at the firm being a random variable. We characterize the asymptotic behaviors of the optimal investments in both heavy and light trading environments. We show that when the market is very liquid, that is, it is subject to heavy transaction volumes, it is optimal for a financial firm that is highly risk sensitive to use a balanced investment strategy. Both a heavier right tail of the distribution of transaction volume and a firm's risk sensitivity necessitate larger investments; in a heavy trading environment these two factors reinforce one another. However, in a light trading environment with the transaction volume having a heavy left tail the investment will be independent of the firm's sensitivity to risk.
Early warning scores use vital signs to identify patients at risk of critical illness. The current study examines the Hamilton Early Warning Score (HEWS) at emergency department (ED) triage among patients who experienced a critical event during their hospitalization. HEWS was also evaluated as a predictor of sepsis.
The study population included admissions to two hospitals over a 6-month period. Cases experienced a critical event defined by unplanned intensive care unit admission, cardiopulmonary resuscitation, or death. Controls were randomly selected from the database in a 2-to-1 ratio to match cases on the burden of comorbid illness. Receiver operating characteristic (ROC) curves were used to evaluate HEWS as a predictor of the likelihood of critical deterioration and sepsis.
The sample included 845 patients, of whom 270 experienced a critical event; 89 patients were excluded because of missing vitals. An ROC analysis indicated that HEWS at ED triage had poor discriminative ability for predicting the likelihood of experiencing a critical event 0.62 (95% CI 0.58-0.66). HEWS had a fair discriminative ability for meeting criteria for sepsis 0.77 (95% CI 0.72-0.82) and good discriminative ability for predicting the occurrence of a critical event among septic patients 0.82 (95% CI 0.75-0.90).
This study indicates that HEWS at ED triage has limited utility for identifying patients at risk of experiencing a critical event. However, HEWS may allow earlier identification of septic patients. Prospective studies are needed to further delineate the utility of the HEWS to identify septic patients in the ED.
This work presents the effects of sintering temperature and mechanical milling on the weight loss of the powder metallurgical Fe–28Mn–3Si (wt%) alloy. Mechanically milled (MM) and blended elemental (BE) Fe–28Mn–3Si powder mixtures were prepared. Both the MM and BE compacts were sintered in a vacuum furnace for 3 h at various temperatures. It was found that weight loss occurred among all the sintered compacts. The weight loss of the sintered MM compacts was much lower than their BE counterparts sintered at the same temperature. The weight loss of the compacts was mainly caused by the sublimation of Mn in the Mn depletion region. A single α-Fe phase was observed on the surface of all the sintered samples. Predominant γ-austenite and minor ε-martensite were detected in all the sintered compacts at locations beyond the Mn depletion region. Mn3Si phase was found in BE alloys sintered at 1000 °C.
The steady-state nearly resonant water waves with time-independent spectrum in deep water are obtained from the full wave equations for inviscid, incompressible gravity waves in the absence of surface tension by means of a analytic approximation approach based on the homotopy analysis method (HAM). Our strategy is to mathematically transfer the steady-state nearly resonant wave problem into the steady-state exactly resonant ones. By means of choosing a generalized auxiliary linear operator that is a little different from the linear part of the original wave equations, the small divisor, which is unavoidable for nearly resonant waves in the frame of perturbation methods, is avoided, or moved far away from low wave frequency to rather high wave frequency with physically negligible wave energy. It is found that the steady-state nearly resonant waves have nothing fundamentally different from the steady-state exactly resonant ones, from physical and numerical viewpoints. In addition, the validity of this HAM-based analytic approximation approach for the full wave equations in deep water is numerically verified by means of the Zakharov’s equation. A thought experiment is discussed, which suggests that the essence of the so-called ‘wave resonance’ should be reconsidered carefully from both of physical and mathematical viewpoints.
Gradient plasticity provides an effective theoretical framework to interpret
heterogeneous and irreversible deformation processes on micron and submicron
scales. By incorporating internal length scales into a plasticity framework,
gradient plasticity gives access to size effects, strain heterogeneities at
interfaces, and characteristic lengths of strain localization. To relate the
magnitude of the internal length scale to parameters of the dislocation
microstructure of the material, 3D discrete dislocation dynamics (DDD)
simulations were performed for tricrystals of different dislocation source
lengths (100, 200, and 300 nm). Comparing the strain profiles deduced from DDD
with gradient plasticity predictions demonstrated that the internal length scale
depends on the flow-stress-controlling mechanism. Different dislocation
mechanisms produce different internal lengths. Furthermore, by comparing a
gradient plasticity framework with interfacial yielding to the simulations it
was found that, even though in the DDD simulations grain boundaries (GBs) were
physically impenetrable to dislocations, on the continuum scale the assumption
of plastically deformable GBs produces a better match of the DDD data than the
assumption of rigid GBs. The associated effective GB strength again depends on
the dislocation microstructure in the grain interior.
The internal micro/nano-structure of anisotropically oriented polymer/CNTs composites determines their macroscopic properties. However, the connections between the two are not fully understood. The varying of CNT concentration, preparation method, and a thermodynamic parameter (e.g. temperature) can all play interconnected role. In this work, the macroscopic electrical conductivity was measured perpendicular to the film thickness of an insulating polymer (isotactic PolyPropylene, iPP) and a nano-composite of iPP with 5 weight percent of CNT. The thin films studied were sheared (anisotropically nano-structured) and non-sheared (with random internal structure). In general the effect of melt shearing induces anisotropy on the electrical transport properties of the iPP/CNT films in directions parallel and perpendicular to the direction of orientation. Our results show that for the pure iPP, resistivity slightly increases with shear at higher temperatures. When CNTs are introduced, there is a large difference between the resistivity of the sheared and non-sheared nanocomposite. The sheared PNCs when the CNTs are aligned parallel to each other, have higher resistivity, which is possibly due to the higher concentration at which the percolation threshold occurs in this arrangement. The resistivity decreases overall, as the temperature increases from 0 to 50 °C. These results show that CNTs can be used to control and fine tune the desired macroscopic physical properties of nanocomposites, by concentration and orientation, such as electrical conductivity, for applications where such properties are necessary.