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We have examined the requirements for virus transcription and replication and thus the roles of input and progeny genomes in the generation of interferon (IFN)-inducing pathogen-associated molecular patterns (PAMPs) by influenza A viruses using inhibitors of these processes. Using IFN regulatory factor 3 (IRF3) phosphorylation as a marker of activation of the IFN induction cascade that occurs upstream of the IFN-β promoter, we demonstrate strong activation of the IFN induction cascade in A549 cells infected with a variety of influenza A viruses in the presence of cycloheximide or nucleoprotein (NP) small interfering RNA (siRNA), which inhibits viral protein synthesis and thus complementary ribonucleoprotein (cRNP) and progeny viral RNP (vRNP) synthesis. In contrast, activation of the IFN induction cascade by influenza viruses was very effectively abrogated by treatment with actinomycin D and other transcription inhibitors, which correlated with the inhibition of the synthesis of all viral RNA species. Furthermore, 5,6-dichloro-1-β- d -ribofuranosyl-benzimidazole, an inhibitor that prevents viral RNA export from the nucleus, was also a potent inhibitor of IRF3 activation; thus, both viral RNA synthesis and nuclear export are required for IFN induction by influenza A viruses. While the exact nature of the viral PAMPs remains to be determined, our data suggest that in this experimental system the major influenza A virus PAMPs are distinct from those of incoming genomes or progeny vRNPs. IMPORTANCE The host interferon system exerts an extremely potent antiviral response that efficiently restricts virus replication and spread; the interferon response can thus dictate the outcome of a virus infection, and it is therefore important to understand how viruses induce interferon. Both input and progeny genomes have been linked to interferon induction by influenza viruses. However, our experiments in tissue culture cells show that viral RNA synthesis and nuclear export are required to activate this response. Furthermore, the interferon induction cascade is activated under conditions in which the synthesis of progeny genomes is inhibited. Therefore, in tissue culture cells, input and progeny genomes are not the predominant inducers of interferon generated by influenza A viruses; the major viral interferon inducer(s) still remains to be identified.

Management of fish populations is often focused on the exploitation of adult fish. Maintaining the habitat requirements of all life stages may also be an important consideration. We investigated the value of structured habitat to juvenile fishes within a northeastern New Zealand harbour using artificial seagrass units (ASUs). Specifically, we deployed ASUs across treatments with high vs. low habitat manipulations. We hypothesised that if the abundance of recruiting juvenile fishes was greater on the high habitat availability treatments this would suggest that the availability of habitat was limiting juvenile fish abundance. Our analyses were focused on the four most abundant fishes that settled on our ASUs: snapper (Pagrus auratus); spotty (Notolabrus celidotus); trevally (Pseudocaranx dentex); and an assemblage of pipefish species. For snapper, spotty and pipefish, abundance was greater on the high habitat availability treatments. This result would be unlikely to occur if the availability of juvenile fis...

France, in particular the Rhone-Alpes region, is one of the three main centres of ragweed (Ambrosia) in Europe. The aim of this study is to develop a gridded ragweed pollen source inventory for all of France that can be used in assessments, eradication plans and by atmospheric models for describing concentrations of airborne ragweed pollen. The inventory combines information about spatial variations in annual Ambrosia pollen counts, knowledge of ragweed ecology, detailed land cover information and a Digital Elevation Model. The ragweed inventory consists of a local infection level on a scale of 0–100% (where 100% is the highest plant abundance per area in the studied region) and a European infection level between 0% and 100% (where 100% relates to the highest identified plant abundance in Europe using the same methodology) that has been distributed onto the EMEP grid with 5 km × 5 km resolution. The results of this analysis showed that some of the highest mean annual ragweed pollen concentrations were recorded at Roussillon in the Rhone-Valley. This is reflected by the inventory, where the European infection level has been estimated to reach 67.70% of the most infected areas in Europe i.e. Kecskemet in central Hungary. The inventory shows that the Rhone Valley is the most heavily infected part of France. Central France is also infected, but northern and western parts of France are much less infected. The inventory can be entered into atmospheric transport models, in combination with other components such as a phenological model and a model for daily pollen release, in order to simulate the dispersion of ragweed pollen within France as well as potential long-distance transport from France to other European countries.

A significant increase in summer temperatures has been observed for the period 1996–2011 in Poznań, Poland. The phenological response of four weed taxa, widely represented by anemophilous species (Artemisia spp., Rumex spp. and Poaceae and Urticaceae species) to this recent climate warming has been analysed in Poznań by examining the variations in the course of airborne pollen seasons. Pollen data were collected by 7-day Hirst-type volumetric trap. Trends in pollen seasons were determined using Mann–Kendall test and Sen’s slope estimator, whereas the relationships between meteorological and aerobiological data were established by Spearman’s rank correlation coefficient. Significant trends in pollen data were detected. The duration of pollen seasons of all analysed taxa increased (from +2.0 days/year for Urticaceae to +3.8 days/year for Rumex), which can be attributed to a delay in pollen season end dates rather than earlier start dates. In addition, the intensity of Artemisia pollen seasons significantly decreased and correlates with mean July–September daily minimum temperatures (r = −0.644, p

The Michigan Department of Transportation (DOT) is interested in new technologies to improve transportation asset management (TAM) practices. A central component of TAM is pavement condition and performance assessment. To investigate methods to improve TAM data collection, the Michigan DOT and the Center for Automotive Research researched the potential for connected vehicle data to contribute to pavement condition and performance assessment. This effort included the review, critical analysis, and synthesis of several research reports and pilot projects to determine feasible methods of using connected vehicle data for pavement condition and performance assessment. The scope of connected vehicle data was defined to include data collected by sensors installed on consumer available vehicles and smartphones. The technology to allow for data capture from embedded vehicle systems and smartphones was established, but implementing such practices into TAM had not yet proved to be practical. One possibility for effe...

The pollen grains of ragweed are important aeroallergens that have the potential to be transported longdistances through the air. The arrival of ragweed pollen in Nordic countries from the Pannonian Plain canoccur when certain conditions are met, which this study aims to describe for the first time. Atmosphericragweed pollen concentrations were collected at 16 pollen-monitoring sites. Other factors included inthe analysis were the overall synoptic weather situation, surface wind speeds, wind direction and tem-peratures as well as examining regional scale orography and satellite observations. Hot and dry weatherin source areas on the Pannonian Plain aid the release of ragweed pollen during the flowering seasonand result in the deep Planetary Boundary Layers needed to lift the pollen over the Carpathian Moun-tains to the north. Suitable synoptic conditions are also required for the pollen bearing air masses tomove northward. These same conditions produce the jet-effect Kosava and orographic foehn winds thataid the release and dispersal of ragweed pollen and contribute towards its movement into Poland andbeyond.

In epidemiological studies, outdoor exposure to pollen is typically estimated using rooftop monitoring station data, whilst exposure overwhelmingly occurs at street level. In this study the relationship between street level and roof level grass pollen concentrations was investigated for city centre street canyon environments in Aarhus, Denmark, and London, UK, during the grass pollen seasons of 2010 and 2011 respectively. For the period mid-day to late evening, street level concentrations in both cities tended to be lower than roof-level concentrations, though this difference was found to be statistically significant only in London. The ratio of street/roof level concentrations was compared with temperature, relative humidity, wind speed and direction, and solar radiation. Results indicated that the concentration ratio responds to wind direction with respect to relative canyon orientation and local source distribution. In the London study, an increase in relative humidity was linked to a significant decrease in street/roof level concentration ratio, and a possible causative mechanism involving moisture mediated pollen grain buoyancy is proposed. Relationships with the other weather variables were not found to be significant in either location. These results suggest a tendency for monitoring station data to overestimate exposure in the canyon environment.

The use of medical expulsive therapy to hasten stone passage potentially decreases expenditures around episodes of renal colic. However, these efficiency gains may be mitigated if patients treated with medical expulsive therapy have frequent health care encounters due to pain while waiting for the stones to pass.Using claims data (2002 to 2006) we identified adult men with acute renal colic. We compared 6-week payments as well as frequency of hospitalization and emergency department revisits associated with an initial course of medical expulsive therapy with those for early endoscopic stone removal. To account for unmeasured confounding we performed an instrumental variable analysis, exploiting variation in recommended treatments based on the day of the week that a patient's first emergency department visit occurred.Overall 1,835 and 4,397 men underwent medical expulsive therapy or early endoscopic stone removal, respectively. Although minimal differences existed between men with respect to the day of the week of emergency department presentation, weekend encounters were strongly associated with receiving medical expulsive therapy (p0.001). Two-stage least squares regression revealed 6-week payments to be tenfold lower for men on medical expulsive therapy who were candidates for either treatment (p0.001). While there was no difference in frequency of hospitalization, these men were more likely to have a repeat emergency department visit compared to those who underwent endoscopic stone removal (68.8% vs 39.6%, respectively, p = 0.025).Findings on medical expulsive therapy are mixed, with lower 6-week payments but more frequent repeat emergency department visits. These data inform patients who are candidates for medical expulsive therapy or endoscopic stone removal when making decisions about their care.

* Ragweed Ambrosia artemisiifolia L. is rapidly spreading in Europe. Its pollen is highly allergenic, with 4–5 of Europeans being sensitized. There is an urgent need to curtail the further spread to minimize allergy costs. * We simulated the spread of ragweed in Austria and southern Germany (Bavaria) until 2050 with particular emphasis on expected climate change. Using different management scenarios and levels of management effort, we analysed the potential for reducing human allergy costs, that is, expenses caused by allergies from ragweed pollen, by curtailing the accelerating spread of ragweed. We accounted for three contrasting climate assumptions: no change in temperature and moderate (annual temperature increase of 0·025 °C) and more extreme (annual temperature increase of 0·04 °C) climate change. * We found that a carefully designed management plan consisting of survey and eradication can drastically reduce the spread of ragweed. Without management, mean allergy costs for the management period (2011–2050) amount to about 290, 335 and 365 million € annually under the three climate change assumptions. * Following an optimally allocated management strategy with an annual budget of 30 million € reduces mean allergy costs by 258, 295 and 325 million € per year. Thus, the management may yield substantial savings, in particular under more extreme warming, where total savings over 40 years amount to about 12 billion €. * Synthesis and applications. Our study illustrates that management of invasive alien species has an economic benefit beside natural conservation. We provide guidance for the future management using the example of ragweed in Austria and Bavaria and show that although the species has expanded its range and abundance substantially in recent years, a well-designed and ambitious management programme still may yield substantial benefits. This is true for current climatic conditions as well as for future climate change scenarios, albeit management costs increase with a warming climate. However, possible gains are increasing in parallel. Given the scale of impacts on human health, and the substantial gains accrued from management, our results suggest that it is wise to halt further spread of ragweed.

Estuarine and sheltered coastal habitats that contain physical structure are potentially important nurseries for juvenile fish. Many of these structured habitats, however, are potentially vulnerable to stressors such as elevated turbidity. Quantifying the benefits that structured habitats provide to juvenile fish may therefore be an important step in the management process. We investigated the value of structured habitat for juvenile fishes in northeastern New Zealand, using artificial seagrass units (ASUs) with varying blade density. ASUs were predominantly settled by juvenile snapper (Pagrus auratus) and spotty (Notolabrus celidotus). The density of both snapper and spotty was greatest on ASUs with the highest blade density. For snapper, a gradient in abundance was present (with higher abundance closer to the harbour mouth), suggesting either a gradient in the supply of recruits or a potential recruitment shadow effect. The size distribution of juvenile snapper (12–70 mm fork length) was very similar on both sampling trips, despite the 2-month interim period, suggesting an ontogenetic habitat shift dependent on size. The condition of juvenile snapper from ASUs with the highest blade density was also greater than the other ASU treatments. Overall, these results provide new empirical evidence that habitats with physical structure within shallow estuarine systems are important to early stage juvenile fishes such as snapper, and indicate that the location-specific context of that habitat is also likely important.

The patient’s hay-fever diary (PHD) is a newly developed, internet-based tool for self-documentation of pollen-induced symptoms (eyes, nose and airways), general well-being and medication use. In Germany, more than 1,600 users made over 60,500 reports in 3 years (2009–2011). An analysis of these reports reveal that the nose symptom “sneezing” is the most commonly reported (3/10 of reports), followed by eye symptom “itching” and nose “blocked”. In addition, medication use follows a similar pattern every year, with tablets being the most commonly used medication type (up to 60 % of the reports made in the years 2009 and 2011). Temporal variations in overall symptoms and organ-specific symptom scores are found to be associated with atmospheric concentrations of birch and grass pollen. Data from the PHD can be analysed with the aid of various mathematical methods and may provide information about symptoms and their severity for pollen-allergic sufferers. They may also be valuable for clinical studies in immunotherapy with pollen extracts.

Pollen is routinely monitored, but it is unknown whether pollen counts represent allergen exposure. We therefore simultaneously determined olive pollen and Ole e 1 in ambient air in Córdoba, Spain, and Évora, Portugal, using Hirst-type traps for pollen and high-volume cascade impactors for allergen. Pollen from different days released 12-fold different amounts of Ole e 1 per pollen (both locations P40% of Ole e 1 exposure in Évora was explained by high-potency pollen originating from the south of Spain. Thus, olive pollen can vary substantially in allergen release, even though they are morphologically identical.

Birch (Betula) pollen seasons were examined in relation to meteorological conditions in Poznan (1996–2010). Birch pollen grains were collected using a volumetric spore trap. An alternate biennial cycle of birch pollen season intensity was noticed in Poznan. The main factors influencing birch pollen season intensity were average daily minimum temperatures during the second fortnight of May and the month of June one year before pollination as well as the intensity of the pollen season of the previous year. Most of the pollen grains are recorded during the first week of the season; the number of pollen grains recorded at this time is positively correlated with mean maximum temperature and negatively correlated with daily rainfall. The significant effect of rainfall in reducing the season pollen index was noticed only during weak pollen seasons (season pollen index

This study presents the findings of a 10-year survey carried out by the Portuguese Aerobiology Network (RPA) at seven pollen-monitoring stations: five mainland stations (Oporto, Coimbra, Lisbon, Évora and Portimão) and two insular stations [Funchal (Madeira archipelago) and Ponta Delgada (Azores archipelago)]. The main aim of the study was to examine spatial and temporal variations in the Annual Pollen Index (API) with particular focus on the most frequently recorded pollen types. Pollen monitoring (2003–2012) was carried out using Hirst-type volumetric spore traps, following the minimum recommendations proposed by the European Aerobiology Society Working Group on Quality Control. Daily pollen data were examined for similarities using the Kruskal–Wallis nonparametric test and multivariate regression trees. Simple linear regression analysis was used to describe trends in API. The airborne pollen spectrum at RPA stations is dominated by important allergenic pollen types such as Poaceae, Olea and Urticaceae. Statistically significant differences were witnessed in the API recorded at the seven stations. Mean API is higher in the southern mainland cities, e.g. Évora, Lisbon and Portimão, and lower in insular and littoral cities. There were also a number of significant trends in API during the 10-year study. This report identifies spatial and temporal variations in the amount of airborne pollen recorded annually in the Portuguese territory. There were also a number of significant changes in API, but no general increases in the amount of airborne pollen.

Allergies due to airborne pollen affect a considerable percentage of Europeans; thus, the provision of health-related information services concerning pollen-induced symptoms can improve the overall quality of life. In this paper, we demonstrate the development of personalized, health-related, quality-of-life information services by adopting a data-driven approach. The data we use consist of allergic symptoms reported by people as well as detailed pollen count information of the most allergenic taxa. We apply computational intelligence methods in order to analyze symptoms, identify possible interrelationships with several pollen taxa and develop models that associate pollen count levels with allergic symptoms on a personal level. The results for the case of Austria show that this approach can lead to accurate personalized symptom forecasting models; we report an average correlation coefficient of r = 0.70 for a sample of 102 users of the Patients Hayfever Diary. We conclude that some of these models could serve as the basis for personalized health information services.

The fight against doping is mainly focused on direct detection, using analytical methods for the detection of doping agents in biological samples. However, the World Anti-Doping Code also defines doping as possession, administration or attempted administration of prohibited substances or methods, trafficking or attempted trafficking in any prohibited substance or methods. As these issues correspond to criminal investigation, a forensic approach can help assessing potential violation of these rules. In the context of a rowing competition, genetic analyses were conducted on biological samples collected in infusion apparatus, bags and tubing in order to obtain DNA profiles. As no database of athletes' DNA profiles was available, the use of information from the location detection as well as contextual information were key to determine a population of suspected athletes and to obtain reference DNA profiles for comparison. Analysis of samples from infusion systems provided 8 different DNA profiles. The comparison between these profiles and 8 reference profiles from suspected athletes could not be distinguished. This case-study is one of the first where a forensic approach was applied for anti-doping purposes. Based on this investigation, the International Rowing Federation authorities decided to ban not only the incriminated athletes, but also the coaches and officials for 2 years.

Knowledge of airborne pollen concentrations and the weather conditions influencing them is important for air quality forecasters, allergists and allergy sufferers. For this reason, a 7-day recording volumetric spore trap of the Hirst design was used for pollen monitoring between January 2006 and December 2007 in Kastamonu, Turkey. A total of 293,427 pollen grains belonging to 51 taxa were recorded during the study period. In the 2 years of study, the period March–August was identified as the main pollination season for Kastamonu. The highest monthly pollen counts were observed in May in both years. Six taxa made up 86.5% of the total amount of pollen recorded in the atmosphere of Kastamonu. These were as follows: Pinaceae (42.9%), Cupressaceae (20.6%), Poaceae (9.7%), Quercus (5.5%) Betula (5.3%) and Carpinus (2.6%). Four of these are considered to be highly allergenic (Betula, Carpinus, Cupressaceae and Poaceae). There were also a greater percentage of highly allergenic taxa found within the city, including Betula pendula that is not part of the local flora. This shows that through urban planting, the public and municipalities can unconsciously create a high risk for allergy sufferers. Daily average pollen counts from the six most frequently recorded pollen types were entered into Spearman’s correlation analysis with meteorological data. Mean daily temperature, relative humidity, daily rainfall and wind speed were found to significantly (p < 0.05) affect atmospheric pollen concentrations, but the relationships between pollen concentrations and meteorological variables can vary and so there is a need for more local studies of this nature.

Pollen data have been recorded at Novi Sad in Serbia since 2000. The adopted method of producing pollen counts has been the use of five longitudinal transects that examine 19.64% of total sample surface. However, counting five transects is time consuming and so the main objective of this study is to investigate whether reducing the number to three or even two transects would have a significant effect on daily average and bi-hourly pollen concentrations, as well as the main characteristics of the pollen season and long-term trends. This study has shown that there is a loss of accuracy in daily average and bi-hourly pollen concentrations (an increase in % ERROR) as the sub-sampling area is reduced from five to three or two longitudinal transects. However, this loss of accuracy does not impact on the main characteristics of the season or long-term trends. As a result, this study can be used to justify changing the sub-sampling method used at Novi Sad from five to three longitudinal transects. The use of two longitudinal transects has been ruled out because, although quicker, the counts produced: (a) had the greatest amount of % ERROR, (b) altered the amount of influence of the independent variable on the dependent variable (the slope in regression analysis) and (c) the total sampled surface (7.86%) was less than the minimum requirement recommended by the European Aerobiology Society working group on Quality Control (at least 10% of total slide area).

Previous studies have shown that ragweed pollen arrives in Poland from sources in the south, in Slovakia, the Czech Republic, Hungary and Austria. It is likely that ragweed pollen also arrives from sources in the southeast (e.g. Ukraine). This hypothesis was investigated using 13 years of pollen data and back-trajectory analysis. Ambrosia pollen data were collected at three sites in Poland, Rzeszów, Kraków and Poznań. The amount of ragweed pollen recorded at Rzeszów was significantly higher than in Poznań and Kraków. This can be related to either a higher abundance of local populations of Ambrosia in south-east Poland or the proximity of Rzeszów to foreign sources of ragweed pollen. The combined results of pollen measurements and air mass trajectory calculations identified plumes of Ambrosia pollen that were recorded at Rzeszów, Kraków and Poznań on 4 and 5 September 1999 and 3 September 2002. These plumes arrived at the pollen-monitoring sites from an easterly direction, indicating sources of Ambrosia pollen in eastern Poland or Ukraine. This identifies Ukraine as a possible new source of ragweed pollen for Poland and therefore an important source area of Ambrosia pollen on the European Continent.

Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and the molecular heterogeneity within TNBC heightens the challenge of developing effective targeted therapies. Receptor tyrosine kinases (RTKs), in particular MET and EGFR, are promising therapeutic targets for TNBC due to their high expression in multiple molecular TNBC subtypes and the tendency for cancers to become “kinase addicted.” We and others have demonstrated that MET is highly expressed in TNBC and its expression correlates with poor prognosis. EGFR expression is also elevated in up to 72% of TNBCs and correlates with poor prognosis in TNBC patients. Recently, we demonstrated that MET and EGFR are coordinately and highly expressed across all TNBC subtypes and the efficacy of combined MET and EGFR inhibition in TNBC patient-derived xenograft (PDX) models. Even though MET and EGFR receptors are actionable targets due to their high activity in TNBC, crosstalk between MET and EGFR has been implicated in therapeutic resistance to kinase inhibitors in several cancer types and needs to be evaluated in TNBC. There is strong evidence demonstrating the critical role of redundant RTK signaling networks in resistance to tyrosine kinase inhibitors (TKIs). Specifically, crosstalk between MET and EGFR has been implicated in therapeutic resistance to EGFR or MET inhibitors in colon, gastric, and lung cancers. Since MET and EGFR are highly expressed in a substantial proportion of TNBCs, we used TNBC PDX models and TNBC cell lines to interrogate mechanisms of resistance to MET and EGFR kinase inhibition. We hypothesized that coexpression, interaction, and activation of MET and EGFR promote acquired TKI resistance and an adaptive kinome response in TNBC. Using TNBC PDX models that highly express both MET and EGFR, we evaluated MET and EGFR activity, localization, and interaction after 3 days or 3 weeks of treatment with MET (glesatinib, crizotinib) and/or EGFR inhibitors (erlotinib). After 3 weeks of dual MET and EGFR inhibition in TNBC PDXs, only a small population of “resistant” cells remained. In these resistant populations, we observed increased MET and EGFR colocalization and increased MET and EGFR activation. To understand how colocalization of MET and EGFR promotes signaling redundancy and crosstalk, we asked whether MET and EGFR directly interact in TNBC PDX using a proximity ligation assay (PLA). PLA uses antibody specificity to detect direct protein-protein interactions at physiologic levels in vitro and in vivo. We observed a significant increase in MET EGFR interactions only in resistant cell populations that had been treated with both MET and EGFR inhibitors. AKT and ERK signaling were also increased in TKI-resistant cells, indicating that these are key survival pathways in resistance. Interestingly, we did not observe an increase in MET-EGFR activity or interaction in PDX tumors treated for only 3 days. Even though TNBC cells (HCC70) showed increased colocalization of MET and EGFR with combined glesatinib and erlotinib treatment, there was not a significant increase in MET-EGFR interactions. Evaluation of MET-EGFR interaction in primary TNBC patient samples revealed significant MET-EGFR interactions in a MET-amplified tumor and lymph node metastases. To our knowledge, this is the first time MET-EGFR interactions have been observed in TNBC in vivo and in human patients. Moreover, MET-EGFR interactions are able to maintain MET, EGFR, ERK, and AKT activity through a yet-unknown mechanism. These results imply that MET EGFR interaction may be a unique mechanism of resistance to kinase inhibition that may be inherent in human TNBCs with genomic amplification of MET or EGFR. Citation Format: Elizabeth Tovar, Curt Essenburg, Anderson Peck, Lisa Turner, Zachary Madaj, Matthew Smith, James Christensen, Marianne Melnik, Eric Haura, Matthew Steensma, Carrie Graveel. MET and EGFR interaction promotes acquired resistance to kinase inhibition in TNBC [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A48.

Circulating tumor DNA (ctDNA) analysis enables minimally invasive assessment of somatic genetic alterations for cancer patients. ctDNA analysis is quickly being incorporated into cancer care; notably in profiling patients' tumors to guide treatment decisions. Patients have demonstrated a response to targeted therapies even when the actionable mutations detected in their plasma DNA was at low variant allele fractions (VAFs) (< 0.5%). Here we describe a detailed analytical validation study for InVisionFirst™, an NGS-based assay offering broad molecular profiling with exceptional sensitivity for analysis of ctDNA. The InVisionFirst assay is based on enhanced tagged amplicon sequencing (eTAm-SeqTM) technology and profiles 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations. Analytical validation demonstrated the performance of this assay for detection of point mutations, indels, amplifications and gene fusions that commonly occur in NSCLC. Over 100 different contrived samples and 200 plasma samples were analyzed, representing a wide spectrum of genetic aberrations and variant allele frequency (VAF). Analysis was performed by multiple operators, at different times and using different reagent lots. The InVisionFirst assay demonstrated an excellent sensitivity, with 99.48% sensitivity for SNVs present at VAF range 0.25%-0.33% and 92.46% sensitivity for indels at 0.25% VAF. DNA amplifications for ERBB2, FGFR1, MET and EGFR were also detected with high sensitivity and specificity. Greater than 50% of SNVs were detected down to a few molecules (0.06%-0.08% VAF), with the lower reportable range of 0.0125% for SNVs and indels. This high sensitivity was achieved while still retaining exceptional specificity (99.9997% per base). The assay also demonstrates, for the first time, detection of ALK and ROS1 gene fusions with an amplicon-based ctDNA technology. The novel methodology detected EML4-ALK and SLC34A2-ROS1 breakpoints at a VAF of 0.0625%. Comparison of VAFs between the InVisionFirst assay and ddPCR showed excellent concordance (R2 = 0.965). This analytical validation study has evaluated the performance characteristics of the InVisionFirst assay across a range of genomic alterations, establishing it as a highly sensitive and specific assay that meets the analytical requirements for clinical applications. The InVisionFirst assay can be deployed as a liquid biopsy NGS assay for broad molecular profiling of plasma to aid in the management of cancer patients. Citation Format: Samuel Woodhouse, Vincent Plagnol, Karen Howarth, Stefanie Lensing, Matt Smith, Michael Epstein, Mikidache Madi, Sarah Smalley, Catherine Leroy, Jonathan Hinton, Frank de Kievit, Esther Musgrave-Brown, Colin Herd, Katherine Baker-Neblett, Will Brennan, Peter Dimitrov, Nathan Campbell, Nitzan Rosenfeld, James Clark, Davina Gale, Jamie Platt, John Calaway, Greg Jones, Tim Forshew. Analytical validation of InVisionFirst™, a liquid biopsy assay for high-sensitivity broad molecular profiling of circulating tumor DNA using plasma samples of cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 939.

The development of impedance-based array devices is hindered by a lack of robust platforms and methods upon which to evaluate and interrogate sensors. One aspect to be addressed is the development of measurement-time efficient techniques for broadband impedance spectroscopy of large electrode arrays. The objective of this work was to substantially increase the throughput capability of low frequency impedance measurement of a large channel-count array analyzer by developing true parallel measurement methods. The goal was achieved by Fourier transform-based analysis of simultaneously-acquired, multi-channel current and voltage data. Efficacy and quantitative analysis of the parallel approach is demonstrated through impedance measurements of dummy cell arrays to sub-Hertz frequencies. Comparison of the accuracy and measurement-time efficiency of the standard-only sequential measurement method and a hybrid high-frequency standard + low frequency parallel approach highlights the efficacy of the latter method when applied to large arrays.

Recent changes in the seasonal timing (phenology) of familiar biological events have been one of the most conspicuous signs of climate change. However, the lack of a standardized approach to analysing change has hampered assessment of consistency in such changes among different taxa and trophic levels and across freshwater, terrestrial and marine environments. We present a standardized assessment of 25 532 rates of phenological change for 726 UK terrestrial, freshwater and marine taxa. The majority of spring and summer events have advanced, and more rapidly than previously documented. Such consistency is indicative of shared large scale drivers. Furthermore, average rates of change have accelerated in a way that is consistent with observed warming trends. Less coherent patterns in some groups of organisms point to the agency of more local scale processes and multiple drivers. For the first time we show a broad scale signal of differential phenological change among trophic levels; across environments advances in timing were slowest for secondary consumers, thus heightening the potential risk of temporal mismatch in key trophic interactions. If current patterns and rates of phenological change are indicative of future trends, future climate warming may exacerbate trophic mismatching, further disrupting the functioning, persistence and resilience of many ecosystems and having a major impact on ecosystem services.

Relationships between temporal variations in the North Atlantic Oscillation (NAO) and grass pollen counts at 13 sites in Europe, ranging from Cordoba in the south-west and Turku in the north-east, were studied in order to determine spatial differences in the amount of influence exerted by the NAO on the timing and magnitude of grass pollen seasons. There were a number of significant (P < 0.05) relationships between the NAO and start dates of the grass pollen season at the 13 pollen-monitoring sites. The strongest associations were generally recorded near to the Atlantic coast. Several significant correlations also existed between winter averages of the NAO and grass pollen season severity. Traditional methods for predicting the start or magnitude of grass pollen seasons have centred on the use of local meteorological observations, but this study has shown the importance of considering large-scale patterns of climate variability like the NAO.

This project/workshop report introduces the ways Matt Smith and PickleHerring Theatre approaches community puppetry. The report emphasizes the group experience, the participants' play and the levels of creativity in the workshops/projects. The efficacy of puppetry as an important form of community arts practice is given in the summary.

Geographic information systems (GIS) analysis considering size and spatial distribution of infestations of invasive species on a landbase can assist with developing appropriate control strategies for that species. We used GIS to evaluate strategies that placed highest priority on: smallest patches of cogongrass, largest patches of cogongrass, and cogongrass patches on land considered high-value under military training and conservation priorities on Camp Shelby Joint Forces Training Center (CSJFTC), MS. Strategies were first evaluated using predicted increase in area of new growth prevented, if prioritized patches were treated with herbicide. Travel and other time needed to implement strategies were then assessed as they affected total area treated. Assuming equivalent areas treated, predicted total reduction in area was consistently highest for the strategy prioritizing smallest patches and lowest for the strategy prioritizing largest patches. However, travel and other time was sufficiently reduced for the strategy prioritizing patches on high-value land compared to the other strategies to suggest that this strategy would result in the greatest reduction in area infested with cogongrass. Analyses of spatial distribution and size of infestations can assist land managers with selecting the appropriate strategy for controlling invasive species.

The long-range transport of Ambrosia pollen to Poland is intermittent and mainly related to the passage of air masses over the Carpathian and Sudetes mountains. These episodes are associated with hot dry weather, a deep Planetary Boundary Layer (PBL) in the source areas and winds from the south. Such episodes can transport significant amounts of Ambrosia pollen into Poland. The study investigates Ambrosia pollen episodes at eight sites in Poland during the period 7th to 10th September 2005, by examining temporal variations in Ambrosia pollen and back-trajectories. PBL depths in the likely source areas were calculated with the Eta meteorological model and evaluated against the mountain heights. Considerable amounts of Ambrosia pollen were recorded at several monitoring sites during the night or early in the morning of the investigated period. Trajectory analyses shows that the air masses arriving at the Polish sites predominantly came from the south, and were in the Czech Republic, Slovakia and Hungary the previous day indicating these countries as potential source areas. We have shown the progress of Ambrosia plumes into Poland from the south of the country, probably from Slovakia and Hungary, and demonstrated how Lagrangian back-trajectory models and meteorological models can be used to identify possible transport mechanisms of Ambrosia pollen from potential source regions.

This project report describes the way PickleHerring Theatre approaches community music-making with ‘junk’ materials. The report has an emphasis on the group experience, the participants' creativity, and their play. In conclusion a case is presented for the efficacy of junk music-making as a dynamic form of community music.

On 17th March 2006 an Improvised Explosive Device damaged a manifold on a pipeline, resulting in a release of Brass River crude into the Brass River itself. As soon as the spill was noticed the pipeline was shut down and the resultant release was contained by a series of booms, although an undefined amount escaped into the river. Over flights revealed a large volume of black oil from a position north of the manifold down to the mouth of the river. This was located to the eastern shoreline, with a sheen extending though out the river and extending approximately 6 kilometres offshore. It was estimated that a volume of 8000 to 9000 barrels of oil could have spilt into the river. The objectives for the personnel attending were to;Determine the fate of the oilDetermine the environmental impacts of the oil on the topography of the areaDetermine near shore and shoreline impacted areasGive technical advice to optimise time and resources for maximum oil recovery The area around the Brass River is mainly mangrove swamps and tree forests with several local communities situated adjacent to areas of sandy beach. The paper discusses the review and choice of appropriate spill management strategies; namely: mechanical recoveries, monitor & evaluate, contain & collect. It will also look in to the initial estimation and quantification of the spill as well as tracking the recorded volumes of oil throughout the duration of the spill. It concludes that the use of booms to contain the oil and then use a recovery device to recover the oil was the correct course of action to take with any black oil that escaped requiring manual clean-up either in the river or on the beach areas. The paper discusses the effectiveness of the interface with the local Tier 2 contractor, the client and the local authorities and also reviews the security measures that were in place for expatriate personnel, especially when outside guarded facilities.

Airborne concentrations of Poaceae pollen have been monitored in Poznan for more than ten years and the length of the dataset is now considered sufficient for statistical analysis. The objective of this paper is to produce long-range forecasts that predict certain characteristics of the grass pollen season (such as the start, peak and end dates of the grass pollen season) as well as short-term forecasts that predict daily variations in grass pollen counts for the next day or next few days throughout the main grass pollen season. The method of forecasting was regression analysis. Correlation analysis was used to examine the relationship between grass pollen counts and the factors that affect its production, release and dispersal. The models were constructed with data from 1994-2004 and tested on data from 2005 and 2006. The forecast models predicted the start of the grass pollen season to within 2 days and achieved 61% and 70% accuracy on a scale of 1-4 when forecasting variations in daily grass pollen counts in 2005 and 2006 respectively. This study has emphasised how important the weather during the few weeks or months preceding pollination is to grass pollen production, and draws attention to the importance of considering large-scale patterns of climate variability (indices of the North Atlantic Oscillation) when constructing forecast models for allergenic pollen.