SOUTHERNMOST OCCURRENCE OF THE SUWANNEE COOTER, PSEUDEMYS CONCINNA SUWANNIENSIS (TESTUDINES: EMYDIDAE)

The Suwannee Cooter, Pseudemys concinna suwanniensis, the largest member of the speciose turtle family Emydidae, inhabits a small number of rivers that drain into the northeastern Gulf of Mexico along the northwest coast of Florida from just west of Tallahassee to just south of Tampa. The status of this state-protected subspecies in the southernmost of these rivers, the Alafia, is unknown and hence of conservation concern. We provide recent evidence confirming that a reproducing population still exists in this river, and review available specimens and both published and unpublished records documenting the southern limit of distribution. At least within the eastern United States, our observations also extend confirmed knowledge of the geographic occurrence of hatchling turtles overwintering in the nest southward by 285 km

DISTRIBUTION AND STATUS OF THE SUWANNEE COOTER, PSEUDEMYS CONCINNA SUWANNIENSIS, IN THE ALAFIA RIVER (HILLSBOROUGH COUNTY, FLORIDA, USA)

The Suwannee Cooter, Pseudemys concinna suwanniensis, is a geographically limited turtle of conservation concern that inhabits Florida rivers draining into the northeastern Gulf of Mexico. Threats impacting its conservation status include take for human consumption, predation of turtles and nests, loss or degradation of nesting and basking habitat, water quality degradation, and boat strikes. Our surveys revealed that the Alafia River, which drains into Hillsborough Bay (northeastern Tampa Bay), is likely the stronghold of the southern distribution of P. c. suwanniensis. Multiple survey methods during 2015-2020 revealed that a substantial population of Suwannee Cooters inhabits much of this blackwater river system, including the main channel and at least one of its two primary tributaries. GIS analysis showed that more than half of the shoreline within the occupied extent is currently protected by conservation lands, although additional protection of private lands and improved habitat management protocols are needed to assure the population’s conservation

Second-order finite volume with hydrostatic reconstruction for tsunami simulation

Tsunami modeling commonly accepts the shallow water system as governing equations where the major difficulty is the correct treatment of the nonconservative term due to bathymetry variations. The finite volume method for solving the shallow water equations with such source terms has received great attention in the two last decades. The built-in conservation property, the capacity to correctly treat discontinuities, and the ability to handle complex bathymetry configurations preserving some steady state configurations (well-balanced scheme) make the method very efficient. Nevertheless, it is still a challenge to build an efficient numerical scheme, with very few numerical artifacts (e.g., small numerical diffusion, correct propagation of the discontinuities, accuracy, and robustness), to be used in an operational environment, and that is able to better capture the dynamics of the wet-dry interface and the physical phenomena that occur in the inundation area. In the first part of this paper, we present a new second-order finite volume code. The code is developed for the shallow water equations with a nonconservative term based on the hydrostatic reconstruction technology to achieve a well-balanced scheme and an adequate dry/wet interface treatment. A detailed presentation of the numerical method is given. In the second part of the paper, we highlight the advantages of the new numerical technique. We benchmark the numerical code against analytical, experimental, and field results to assess the robustness and the accuracy of the numerical code. Finally, we use the 28 February 1969 North East Atlantic tsunami to check the performance of the code with real data.Historical data for Cascais and Lagos (1969 Lisbon Tsunami) are available at http://www.dgterritorio.pt/cartografia_e_geodesia/geodesia/redes_geodesicas/rede_maregrafica/. The tagus estuary data (typewriter document) are available at the Dom Luiz Institute library http://idl.ul.pt/node/33. This work is funded by the Portugal-France research agreement, through the research project GEONUM FCT-ANR/MAT-NAN/0122/2012. This research was financed by Portuguese Funds through FCT-Fundacao para a Ciencia e a Tecnologia, within the Project UID/MAT/00013/2013

Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour

AbstractBackgroundGastrointestinal stromal tumours (GIST) treated with the tyrosine kinase inhibitor (TKI) imatinib can become resistant when additional mutations in the receptor tyrosine kinases KIT or PDGFRA block imatinib activity. Mutated KIT requires the molecular chaperone heat-shock protein 90 (HSP90) to maintain stability and activity. Onalespib (AT13387) is a potent non-ansamycin HSP90 inhibitor. We hypothesised that the combination of onalespib and imatinib may be safe and effective in managing TKI-resistant GIST.Patients and methodsIn this dose-escalation study, we evaluated the safety and efficacy of combination once-weekly intravenous onalespib for 3 weeks and daily oral imatinib in 28-d cycles. Twenty-six patients with TKI-resistant GIST were enrolled into four sequential dose cohorts of onalespib (dose range, 150–220 mg/m2) and imatinib 400 mg. The relationship between tumour mutational status (KIT/PDGFRA) and efficacy of treatment was explored.ResultsCommon onalespib-related adverse events were diarrhoea (58%), nausea (50%), injection site events (46%), vomiting (39%), fatigue (27%), and muscle spasms (23%). Overall, 81% of patients reported more than one onalespib-related gastrointestinal disorder. Nine patients (35%) had a best response of stable disease, including two patients who had KIT mutations known to be associated with resistance to imatinib and sunitinib. Disease control at 4 months was achieved in five patients (19%), and median progression-free survival was 112 d (95% confidence interval 43–165). One patient with PDGFRA-mutant GIST had a partial response for more than 376 d.ConclusionThe combination of onalespib plus imatinib was well tolerated but exhibited limited antitumour activity as dosed in this TKI-resistant GIST patient population.Trial registration ID: clinicaltrials.gov: NCT0129420

Avapritinib versus regorafenib in locally advanced unresectable or metastatic GI stromal tumor: A randomized, open-label phase III study

PURPOSE Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study (NCT02508532), avapritinib showed clinical activity against PDGFRA D842V–mutant and later-line KIT-mutant GIST. VOYAGER (NCT03465722), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS Four hundred seventy-six patients were randomly assigned (avapritinib, n 5 240; regorafenib, n 5 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P 5 .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade $ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration

Recoil and Threshold Corrections in Short-distance Cross Sections

We identify and resum corrections associated with the kinematic recoil of the hard scattering against soft-gluon emission in single-particle inclusive cross sections. The method avoids double counting and conserves the flow of partonic energy. It reproduces threshold resummation for high-p_T single-particle cross sections, when recoil is neglected, and Q_T-resummation at low Q_T, when higher-order threshold logarithms are suppressed. We exhibit explicit resummed cross sections, accurate to next-to-leading logarithm, for electroweak annihilation and prompt photon inclusive cross sections.Comment: minor modifications of the text, some references added. 51 pages, LaTeX, 6 figures as eps file

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13