Showing papers by "James Taylor published in 2019"

Managing nitrogen to restore water quality in China

Abstract: The nitrogen cycle has been radically changed by human activities1. China consumes nearly one third of the world’s nitrogen fertilizers. The excessive application of fertilizers2,3 and increased nitrogen discharge from livestock, domestic and industrial sources have resulted in pervasive water pollution. Quantifying a nitrogen ‘boundary’4 in heterogeneous environments is important for the effective management of local water quality. Here we use a combination of water-quality observations and simulated nitrogen discharge from agricultural and other sources to estimate spatial patterns of nitrogen discharge into water bodies across China from 1955 to 2014. We find that the critical surface-water quality standard (1.0 milligrams of nitrogen per litre) was being exceeded in most provinces by the mid-1980s, and that current rates of anthropogenic nitrogen discharge (14.5 ± 3.1 megatonnes of nitrogen per year) to fresh water are about 2.7 times the estimated ‘safe’ nitrogen discharge threshold (5.2 ± 0.7 megatonnes of nitrogen per year). Current efforts to reduce pollution through wastewater treatment and by improving cropland nitrogen management can partially remedy this situation. Domestic wastewater treatment has helped to reduce net discharge by 0.7 ± 0.1 megatonnes in 2014, but at high monetary and energy costs. Improved cropland nitrogen management could remove another 2.3 ± 0.3 megatonnes of nitrogen per year—about 25 per cent of the excess discharge to fresh water. Successfully restoring a clean water environment in China will further require transformational changes to boost the national nutrient recycling rate from its current average of 36 per cent to about 87 per cent, which is a level typical of traditional Chinese agriculture. Although ambitious, such a high level of nitrogen recycling is technologically achievable at an estimated capital cost of approximately 100 billion US dollars and operating costs of 18–29 billion US dollars per year, and could provide co-benefits such as recycled wastewater for crop irrigation and improved environmental quality and ecosystem services. Estimates of spatial patterns of nitrogen discharge into water bodies across China between 1955 and 2014 show that current discharge rates are almost three times the acceptable threshold, and ways to restore a clean water environment are suggested.

Forecasting Value at Risk and Expected Shortfall Using a Semiparametric Approach Based on the Asymmetric Laplace Distribution

Abstract: Value at Risk (VaR) forecasts can be produced from conditional autoregressive VaR models, estimated using quantile regression. Quantile modeling avoids a distributional assumption, and allows the dynamics of the quantiles to differ for each probability level. However, by focusing on a quantile, these models provide no information regarding expected shortfall (ES), which is the expectation of the exceedances beyond the quantile. We introduce a method for predicting ES corresponding to VaR forecasts produced by quantile regression models. It is well known that quantile regression is equivalent to maximum likelihood based on an asymmetric Laplace (AL) density. We allow the density's scale to be time-varying, and show that it can be used to estimate conditional ES. This enables a joint model of conditional VaR and ES to be estimated by maximizing an AL log-likelihood. Although this estimation framework uses an AL density, it does not rely on an assumption for the returns distribution. We also use the AL log-l...

A framework for the development of a global standardised marine taxon reference image database (SMarTaR-ID) to support image-based analyses.

Abstract: Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure maps to the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem.

Previsit Screening for Parental Vaccine Hesitancy: A Cluster Randomized Trial.

Abstract: OBJECTIVE: To evaluate the effect of vaccine hesitancy screening on childhood vaccine uptake. METHODS: We conducted a cluster randomized controlled trial in pediatric primary care clinics in Washington state. Vaccine-hesitant parents (VHPs) with a healthy newborn receiving health supervision at participating clinics were eligible. VHPs were identified by using a 4-item version of the validated Parent Attitudes About Childhood Vaccines Survey (PACV). Before their child’s 2- and 6-month health supervision visits, VHPs at intervention clinics completed the 15-item PACV embedded in a survey containing placebo items. Intervention providers received a summary of parents’ 15-item PACV responses and interpretation of their PACV score; discretion was given to providers regarding how they acted on this information. VHPs at control clinics completed only the placebo survey items, and their child’s provider received a summary of their responses; control providers remained blinded to parent VHP status. Our outcome was child immunization status at 8 months of age expressed as percent of days underimmunized. We compared outcomes in control and intervention participants using t test and linear mixed-effects regression. RESULTS: We enrolled 24 clinics (12 in each arm) and 156 parents (65 in the intervention arm). Parent characteristics were similar across arms except more intervention (versus control) parents had a first-born child (60.9% vs 44%; P = .04). No significant difference in outcome was detected between arms (25.2% [95% confidence interval: 16.0% to 34.5%] vs 19.1% [95% confidence interval: 12.0% to 26.3%] mean days underimmunized in the intervention and control arms, respectively). CONCLUSION: Vaccine hesitancy screening was not significantly associated with days underimmunized.

Implementation of a genomic medicine multi-disciplinary team approach for rare disease in the clinical setting: a prospective exome sequencing case series.

Abstract: A multi-disciplinary approach to promote engagement, inform decision-making and support clinicians and patients is increasingly advocated to realise the potential of genome-scale sequencing in the clinic for patient benefit. Here we describe the results of establishing a genomic medicine multi-disciplinary team (GM-MDT) for case selection, processing, interpretation and return of results. We report a consecutive case series of 132 patients (involving 10 medical specialties with 43.2% cases having a neurological disorder) undergoing exome sequencing over a 10-month period following the establishment of the GM-MDT in a UK NHS tertiary referral hospital. The costs of running the MDT are also reported. In total 76 cases underwent exome sequencing following triage by the GM-MDT with a clinically reportable molecular diagnosis in 24 (31.6%). GM-MDT composition, operation and rationale for whether to proceed to sequencing are described, together with the health economics (cost per case for the GM-MDT was £399.61), the utility and informativeness of exome sequencing for molecular diagnosis in a range of traits, the impact of choice of sequencing strategy on molecular diagnostic rates and challenge of defining pathogenic variants. In 5 cases (6.6%), an alternative clinical diagnosis was indicated by sequencing results. Examples were also found where findings from initial genetic testing were reconsidered in the light of exome sequencing including TP63 and PRKAG2 (detection of a partial exon deletion and a mosaic missense pathogenic variant respectively); together with tissue-specific mosaicism involving a cytogenetic abnormality following a normal prenatal array comparative genomic hybridization. This consecutive case series describes the results and experience of a multidisciplinary team format that was found to promote engagement across specialties and facilitate return of results to the responsible clinicians.

An insight into the errors and uncertainty of the lithium-ion battery characterisation experiments

Abstract: Errors and uncertainty within the experimental results have long-term implications in lithium-ion battery research. Experimental directly feed into the development of different battery models, thus having a direct impact on the accuracy of the models, which are commonly employed to forecast short to long term battery performance. The estimations made by such models underpin the design of key functions within the BMS, such as state of charge and state of health estimation. Therefore, erroneous experimental results could evolve into a much larger issue such as the early retirement of a battery pack from the end-use application. For original equipment manufacturers (OEM), such as automotive OEMs this may have a significant impact, e.g. high warranty returns and damage to the brand. Although occasionally reported in published results, currently, little research exists within the literature to systematically define the error and uncertainty of battery experimental results. This article focuses on the fundamental sources of error and uncertainty from experimental setup and procedure and suggests control measures to remove or minimize the contributions from the sources identified. Our research shows that by implementing the control measures proposed, the error and uncertainty can be reduced to around 0.6%, from the figure of around 4.0%.

In-season biomass estimation of oilseed rape (Brassica napus L.) using fully polarimetric SAR imagery

Abstract: Accurate estimation of crop biophysical and biochemical parameters during crop growing seasons is essential for improving site-specific management and yield estimation. The potential ability of fully polarimetric synthetic aperture radar (SAR) data in estimating above-ground biomass of oilseed rape was investigated in this study. The temporal profile of different scattering intensity and polarimetric features during the entire growing season was identified with ground measurements. A polarimetric feature, relying on the polarimetric decomposition method, was put forward to estimate the biomass of oilseed rape. Validation results revealed great potential with a determination coefficient (R2) of 0.85, root mean squared error (RMSE) of 41.6 g/m2, and relative error (RE) of 28.5% for dry biomass, and an R2 of 0.76, RMSE of 527.4 g/m2 and RE of 28.6% for fresh biomass. Moreover, the use of full polarization SAR data was compared with single and dual polarization SAR data. The results suggest that when full polarization SAR data is available, a simpler model, higher saturation point and better accuracy can be achieved in biomass estimation of oilseed rape, which highlights the importance and value of polarimetry information in quantitative crop monitoring. This study provides guidelines for in-season monitoring of crop growth parameters with SAR data, which further improves crop monitoring capability in adverse weather conditions.

Effect of Electronic Screening With Personalized Feedback on Adolescent Health Risk Behaviors in a Primary Care Setting: A Randomized Clinical Trial.

Abstract: Importance Health risk behaviors are a leading cause of morbidity during adolescence. Screening and counseling for health risk behaviors are recommended but infrequently performed. Objective To test the effect of an electronic screening and feedback tool on clinician counseling and adolescent-reported health risk behaviors. Design, Setting, and Participants A randomized clinical trial compared electronic screening and feedback on an intention-to-treat basis with usual care among 300 youths 13 to 18 years of age at 5 pediatric clinics in the Pacific Northwest. Outcomes were assessed via electronic survey at 1 day and 3 months after the initial visit. Study data collection occurred from March 13, 2015, to November 29, 2016, and statistical analysis was conducted between February 6, 2017, and June 20, 2018. Interventions Youths in the intervention group (n = 147) received electronic screening and personalized feedback with clinician clinical decision support. Youths in the control group (n = 153) received standard screening and counseling as provided by their clinic. Main Outcomes and Measures Youths’ report of receipt of counseling during the visit and risk behaviors at 3 months. Results In the final study sample of 300 youths (intervention group, 75 girls and 72 boys; mean [SD] age, 14.5 [1.4 years]; and control group, 80 girls and 73 boys; mean [SD] age, 14.5 [1.4] years), 234 (78.0%) were aged 13 to 15 years. After adjusting for age, sex, and random effect of clinic, youths in the intervention group were more likely to receive counseling for each of their reported risk behaviors than were youths in the control group (adjusted rate ratio, 1.32; 95% CI, 1.07-1.63). Youths in the intervention group had a significantly greater reduction (β = –0.48; 95% CI, –0.89 to –0.02;P = .02) in their risk behavior scores at 3 months when compared with youths in the control group. Conclusions and Relevance Electronic screening of health risk behavior with clinical decision support and motivational feedback to teens can improve care delivery and outcomes. Trial Registration ClinicalTrials.gov identifier:NCT02360410

A comparative review of the state and advancement of Site-Specific Crop Management in the UK and China

Abstract: Precision agriculture, and more specifically Site-Specific Crop Management (SSCM), has been implemented in some form across nearly all agricultural production systems over the past 25 years. Adoption has been greatest in developed agricultural countries. In this review article, the current situation of SSCM adoption and application is investigated from the perspective of a developed (UK) and developing (China) agricultural economy. The current state-of-the art is reviewed with an emphasis on developments in position system technology and satellite-based remote sensing. This is augmented with observations on the differences between the use of SSCM technologies and methodologies in the UK and China and discussion of the opportunities for (and limitations to) increasing SSCM adoption in developing agricultural economies. A particular emphasis is given to the role of socio-demographic factors and the application of responsible research and innovation (RRI) in translating agritechnologies into China and other developing agricultural economies. Several key research and development areas are identified that need to be addressed to facilitate the delivery of SSCM as a holistic service into areas with low precision agriculture (PA) adoption. This has implications for developed as well as developing agricultural economies.

Considerations on spatial crop load mapping

Abstract: Crop load, the ratio of vine size to mass of fruit harvested, is fundamental to viticulture. Measuring vine size and crop yield, the components of crop load, has historically been a labour intensive exercise that has limited the use of crop load information to improve management in vineyards. Recent advances in assessing vine vigour, size and yield using geo‐referenced sensors are starting to make high resolution crop load mapping possible. In this paper, the concept of crop load is revisited with an emphasis on how vine size and yield can be mapped in vineyards. Existing literature is reviewed on how vine size and yield vary spatially and temporally within vineyard blocks and the inference this has on the spatio‐temporal variability of crop load. An example of crop load mapping using sensor technology is presented to illustrate recent advances in sensor technology in viticulture. Finally, some emerging technology and knowledge gaps for implementing spatial crop load information into vineyard management are discussed.

What relevant information can be identified by experts on unmanned aerial vehicles’ visible images for precision viticulture?

Abstract: Unmanned aerial vehicles (UAV) offer interesting alternatives to satellites or airplanes regarding flight agility and image resolution. These sensor platforms may well be used to monitor vines field all throughout the vine’s growing season at a very high spatial resolution. They could provide useful information, different to that normally considered in the literature. To identify the possible uses of UAV images in viticulture, a specific exploratory survey was put into place. This study aimed at identifying (i) relevant information that growers and advisers (G&A) can extract from UAV images and (ii) the added value that this information can have for both G&A’s vineyard management decisions. This approach was conducted on an 11.3 ha commercial vineyard with soil, climate and a training system representative of vineyards in the south of France. UAV-based visible images (25 mm resolution) were acquired every two weeks from budburst to harvest by several UAV companies. Images were shown to a panel of G&As over six sessions during the growing season. Each of these sessions consisted of (i) an individual period during which images were first presented one at a time to each expert and then all together in chronological order from budburst to harvest, and (ii) a collective period during which G&As were asked to share and discuss their point of view. In this exploratory survey, the application of the proposed methodology demonstrated that most of the information on vine status, soil and vineyard environment could be extracted from UAV-based visible images by the experts, thus showing high interest in developing specific image processing techniques to extract this information from images. Results showed that this information was of great interest throughout the growing cycle of the vine, particularly for advisers, as a support to drive management strategies. The outputs of this exploratory study should be confirmed in other contexts than the Languedoc, France region to extrapolate the observed conclusions.

Easy water stress detection system for vineyard irrigation management

Abstract: The monitoring and management of vine water stress is a major issue for many vineyards. A method based on the observation of shoot tip growth makes it possible to determine the water stress of plants without the drawbacks of standard instrumental methods. However, this \"shoot tip\" method is rarely used in the field, as observations and index calculations need to be done manually. Therefore, while the data collection can be relatively quick, data interpretation is not well supported. This article presents a mobile application, ‘Apex’, developed to answer this challenge. The Apex application allows a simple and fast recording of observations and a pooling of spatialized observations. The developed application makes it possible to envisage the collaborative water stress monitoring with crowdsourcing observations.

A simple index to determine if within-field spatial production variation exhibits potential management effects: application in vineyards using yield monitor data

Abstract: As agricultural data and information becomes more abundant, diagnostics are needed to quickly and efficiently interrogate these data. Indices exist to identify sensor data with structured spatial variation, conducive to site-specific management. However, these indices do not indicate if this spatial variation is driven by managerial or environmental effects. A new index is proposed to identify perennial (or ordered row) fields that are likely or highly likely to have management effects within the spatial pattern of sensor data. This is determined by investigating differences in anisotropic (directional) variograms parallel and perpendicular to the direction of management (row orientation). Small differences are indicative of isotropic (environmental-driven) variation. Large differences indicate row and management effects. The index is derived, run on a database of 1080 simulated fields and applied to yield data from 124 vineyard blocks to assess index performance and response to different levels of variation. Simulations showed that the index is non-responsive to the magnitude of variation but responds strongly to anisotropy in the data. The stochastic variance in the data was observed to have an effect on index response and may be problematic when applied to noisy data sets. The index scores for the simulated and real-world data showed a similar pattern of response and the index was able to identify vineyard blocks where differential row management had generated differing yield responses. The index scores are continuous and some general guidelines for use of the index are proposed.

Nanosecond pulsed 620 nm source by frequency-doubling a phosphosilicate Raman fiber amplifier.

Abstract: We demonstrate a nanosecond pulsed source at 620 nm with watt-level average power by frequency-doubling a 1240 nm phosphosilicate Raman fiber amplifier. A gain-switched laser diode operating at 1064 nm is amplified in an ytterbium fiber master oscillator power amplifier system and then converted to 1240 nm using a phosphosilicate Raman fiber amplifier with a conversion efficiency of up to 66%. The Raman fiber amplifier is seeded with a continuous-wave 1240 nm laser diode to obtain narrow-linewidth radiation, which is subsequently frequency-doubled in a periodically poled lithium tantalate crystal. A maximum average power of 1.5 W is generated at 620 nm, corresponding to a pulse energy of 300 nJ at a repetition rate of 5 MHz. The source has excellent beam quality (M2≤1.16) and an optical efficiency (1064 nm to 620 nm) of 20%, demonstrating an effective architecture for generating red pulsed light for biomedical imaging applications.

Automatic harmonization of heterogeneous agronomic and environmental spatial data

Abstract: The analysis and mapping of agronomic and environmental spatial data require observations to be comparable. Heterogeneous spatial datasets are those for which the observations of different datasets cannot be directly compared because they have not been collected under the same set of acquisition conditions, for instance within the same time period (if the variable of interest varies across time), with consistent sensors or under similar management practices (if the management practices impact the measured value) among others. When heterogeneous acquisition conditions take place, there is a need for harmonization procedures to make possible the comparison of such observations. This analysis details and compares four automated methodologies that could be used to harmonize heterogeneous spatial agricultural datasets so that the data can be analysed and mapped conjointly. The theory and derivation of each approach, including a novel, local spatial approach is given. These methods aim to minimize the occurrence of discrepancies (discontinuities) in the data. The four approaches were evaluated and compared with a sensitivity analysis on simulated datasets with known characteristics. Results showed that none of the four methods consistently delivered a better harmonization accuracy. The accuracy and preferred choice for the harmonization procedures was shown to be influenced by (i) within-field spatial structures of the datasets, (ii) differences in acquisition conditions between the heterogeneous spatial datasets, and (iii) the spatial resolution of the simulated data. The four approaches were used to harmonize real within-field grain yield datasets and a discussion to help users select an appropriate harmonization methodology proposed. Despite significant improvements in dataset harmonization, discontinuities were not entirely removed and some uncertainty remained.

Investigating the harmonization of highly noisy heterogeneous datasets hand-collected over the same study domain

Abstract: The objective of this paper is to propose an approach to harmonise noisy spatial data acquired by different operators using (low-cost) hand-held sensors over the same spatial domain. In such cases, datasets need to be harmonised before to be comparable before decision making. This work proposes a methodology to address this issue in the case of nested and noisy spatial data. First, it proposes the implementation of a non-parametric test of Kolmogorov-Smirnov to determine if harmonisation is needed. Then, it proposes an aspatial harmonization method based on a standardization. The method was applied on grape sugar content datasets collected by 2 hand-held spectrometers. Results showed that harmonizing a less confident dataset with respect to a more trustworthy one is interesting solely if the size of the trusted dataset is too small.

Integrating geospatial tools and a crop simulation model to understand spatial and temporal variability of cereals in Scotland

Abstract: The objectives of this study were to: a) quantify the factors causing spatial variability, and b) design a proof of a concept for a support system that considers the impacts of temporal variability. The subdivision of a field based on six years of spatial yield data identified areas with different levels of stable and unstable zones. Overall, in the 0.00.30 m, the soil had between 40 to 60% across all the zones, while at depth, the clay content was about 20% and sand content 30 to 40%. The growing season rainfall for the period 1983-2018 was highly variable, ranging from 152 to 570 mm. The support system showed that there was a general trend where higher growing season rainfall (e.g. 566 mm) corresponded to higher yields, but this meant lower soil nitrogen content at harvest. However, the nitrogen leaching was not always lower and ranged between 20 to 70 kg N ha. Results of this study will enable the development of an agronomic sitespecific N management that would maximize the farm’s net income and minimize the environmental footprint.

Towards Incorporating Within-Field Variation into Spatial Agronomic Decision Processes

Abstract: In this memoire I will present my journey and the knowledge that I have gained within the Precision Agriculture domain over the past two decades. The first section broadly introduces variation in cropping systems and serves as a very general introduction to the research domain. Section 2 provides a more detailed overview of PA and develops some of the main issues and challenges that have been historically faced by PA practitioners. This includes clearly defining the domain and a recognition of the diversity and multi-disciplinary nature of PA. The role and importance of variability in production systems is then introduced along with the challenges in correctly and properly defining production variance. The final three parts of Section 2 turn the focus to how information, particularly multiple layers and multiple types of information, start to be translated into decisions. This shifts PA from a technical question on measuring and managing variation to a socio-technical innovation question on how technology is perceived and adopted and the potential disconnect between what scientists consider important and what commercial users want. Section 3 further develops two key areas – the disconnect between academic research and commercial application (innovation) and the disconnect in the data that we have and what we want (in terms of data type and the quality). There is a deliberate focus on how PA technologies and methodologies are effectively translated into successful commercial services and what I have learnt about this from my various placements and from my attempts to define industry-facing protocols at various stages of my research career. Section 4 provides an overview of how my research activities and publications that have (I hope) helped to address the issues raised in Sections 2 and 3. A focus is given to a large body of work that provides a descriptive reference base to observed spatial variation in yield and crop quality parameters in various annual and perennial systems. This is followed by the role and the evolution in zonage approaches over the past 2 decades and how these zones or management units have been used as a basis for more advantaged analysis to improve crop production knowledge and ultimately crop management decisions. The latter parts of Section 4 shift from natural, agronomic applications to more recent research that has started to interrogate and to build models to understand socio-technical aspects of PA. It develops ideas on how PA translation and adoption can be enhanced by better considering barriers and drivers of adoption. The last section, Section 5, outlines my own vision for the evolution of Precision Agriculture over the next decade. It outlines how Precision Agriculture needs to develop so that producers have a more ‘personalised’ agricultural decision system. It highlights key areas of research that I would like to pursue in my future career, and how advances in digital technology will help to achieve this research and translation. There are some concluding remarks. Throughout the memoire, I have deliberately avoided the incorporation of mathematical notation. I have preferred to keep the discussion more general and not too specific for a broader audience. The cited references contain more specific details for those wishing to understand the derivation of the geostatistical approaches and models discussed. By convention, I have indicated in bold the references that are self-citations within the document. These are all listed in the Bibliography. A more detailed publication list is appended with my full publication list. The publication list contains work that is not cited in the document, particularly research that I have performed in soil science, rather than in PA, and teaching and industry-oriented publications.

A framework for the development of a global standardised marine taxon reference image database (SMarTaR-ID) to support image-based analyses

Abstract: Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure follows the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem.

Bi-allelic MCM10 mutations cause telomere shortening with immune dysfunction and cardiomyopathy

Abstract: Minichromosome maintenance protein 10 (Mcm10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 mutations in patients with distinctive but overlapping clinical phenotypes – natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) with hypoplasia of the spleen and thymus. To understand the mechanism of Mcm10-associated disease, we modeled these mutations in human cell lines. Mcm10 deficiency causes chronic replication stress that reduces cell viability due to increased genomic instability and telomere erosion. Our data suggest that loss of Mcm10 function constrains telomerase activity by accumulating abnormal replication fork structures enriched with single-stranded DNA. Terminally-arrested replication forks in Mcm10-deficient cells require endonucleolytic processing by Mus81, as MCM10:MUS81 double mutants display decreased viability and accelerated telomere shortening. We propose that these bi-allelic mutations in MCM10 predispose specific cardiac and immune cell lineages to prematurely arrest during differentiation, causing the clinical phenotypes in both NKD and CM patients.

Subjective Assessment Underestimates Frailty in Patients with Heart Failure Referred for Advanced Therapies

Abstract: Purpose Objective assessments of frailty using tools like the Modified Fried Frailty Index (mFFI) have been validated in elderly heart failure (HF) populations. However, most programs use a subjective provider assessment (SPA) of frailty, or “eye-ball” test, for patient selection. We compared SPA to mFFI in a cohort of patients referred for evaluation for advanced therapies. Methods Patients referred to our center for evaluation for advanced HF therapies were studied. Those unable to undergo mFFI due to other comorbidities were excluded. mFFI testing assigns a frailty point in each of five domains (weight loss, fatigue, activity, walk time, grip strength). Patients are designated as frail when score ≥3. In addition, three cardiac surgeons independently evaluated and designated patients as frail or not-frail. Surgeons were blinded to designations given by the other surgeons as well as to the mFFI score. Results Over seven months, 19 patients (57±13 yrs) were studied. All patients were assessed by at least one surgeon, 18 by at least two, and 11 by all three. Frailty testing found 47% of patients to be frail as compared to SPA, which found only 0-16% to be frail (p=0.004) (Figure 1). Correlation between subjective and objective assessment was not strong, with providers only agreeing 50-68% of the time with frailty testing (κ Conclusion While agreement between providers is strong, SPA significantly underestimates frailty when compared to formal testing in patients with advanced HF. Further study will determine which approach is optimal for patient selection in this population.

Thu0055 tpl2 inhibition suppresses mek-erk inflammatory signaling and proinflammatory cytokine production in primary human monocytes

Abstract: Background Tumor progression locus 2 (TPL2, also known as MAP3K8) is a mitogen-activated protein kinase kinase kinase and the primary regulator of ERK-mediated gene transcription downstream of multiple proinflammatory stimuli including bacterial products (eg, LPS and bacterial peptidoglycans), damage-associated molecular patterns (DAMPs), TNFα, and IL-1β.1 Dysregulated signaling downstream of these inflammatory signals can drive uncontrolled immune cell activation and inflammation, which is associated with multiple chronic inflammatory and autoimmune diseases. As such, TPL2 inhibition represents a strategy to modulate inflammation in a variety of disease settings. Objectives We evaluated the effect of a highly selective TPL2 inhibitor on inflammatory signaling and cytokine production in LPS and TNFα-stimulated primary human monocytes. Methods Monocytes were precultured with a TPL2 inhibitor and stimulated with LPS or TNFα, and phosphosignaling and cytokine production were then evaluated at 30 minutes and 4 hours poststimulation. A431 cells (human epidermoid carcinoma cell line) were stimulated with TNFα or EGF and phospho–ERK was evaluated after 30 minutes. Results TPL2 inhibition selectively inhibited LPS and TNFα-stimulated phosphorylation of TPL2, MEK, and ERK, with little to no inhibition of phosphorylated p38, JNK, or p65 observed. TPL2 inhibition similarly inhibited both the RNA production and secretion of TNFα, IL-1β, IL-6, and IL-8 following LPS stimulation in primary human monocytes. To confirm TPL2 requirement for inflammatory, but not Ras-mediated (growth factor stimulated) ERK signaling, A431 cells were stimulated with either TNFα or EGF. Although TPL2 inhibition reduced TNFα-stimulated pERK, no effect on ERK activation downstream of EGF was observed. Conclusion This work demonstrates the selective effects of TPL2 inhibition on ERK-mediated signaling and proinflammatory cytokine gene transcription in primary human monocytes and highlights the potential for TPL2 inhibition to treat diseases associated with dysregulated inflammatory signaling and chronic inflammation. Reference [1] Gantke T, Sriskantharajah S, Ley S. Cell Res. 2011;21:131-145. Disclosure of Interests Matthew R. Warr Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Angie Hammond Grant/research support from: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Grace Park Grant/research support from: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Nathan Wright Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., James Taylor Grant/research support from: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc.

Evaluation of shadow effects in satellite images of vineyards with different row orientation

Abstract: In the last few years, the availability of new earth observation satellites, such as Sentinel 2, has increased the interest in their potential for precision agriculture. In a non-continuous crop, like grapevines, the influence of interrow space, and vine geometry can disturb the assessment of vegetation properties using satellites. In particular, vine height and row orientation can project shadows differently, according to the relative solar and sensor position. In this study, sun shading and sensor off-nadir effects were estimated for images acquired by three constellations of satellite (Sentinel 2, RapidEye and Pleiades) on 48 vineyards. Shading and off-nadir effects were calculated using satellite image metadata and vineyard row orientation. Then, multiple linear regression models, based on satellite information and shadows, were estimated using pure vine data extracted from images acquired by a multispectral camera carried by unmanned aerial vehicle as dependent variable. Multiple regression models were compared to simple regression models using different model’s performance parameters (ρ Spearman, R2 adjusted, root mean square error and Akaike’s Information Criteria). The results showed significant effects of sun and off-nadir sensors’ effects on pure vine variability estimation using satellite images, with a stronger effect of sensor orientation than solar shading. In multiple regression models, R2 increased of 5.8, 6.6, and 13.4 % in Pleiades, RapidEye, and Sentinel 2, respectively, compared to simple linear regression models based just on the satellite sensor band data. Moreover, these multiple linear regression models have a better fitting and lower estimation errors than simple linear regressions.

620nm Source by Second Harmonic Generation of a Phosphosilicate Raman Fiber Amplifier

Abstract: We demonstrate a nanosecond-pulsed 620 nm source through frequency doubling a 1240 nm phosphosilicate Raman fiber amplifier. The source emits up to 213 mW of average power, and is repetition rate and pulse duration tunable. © 2019 The Author(s)