Measured fetal and neonatal exposure to Lumacaftor and Ivacaftor during pregnancy and while breastfeeding

With the growing class of CFTR modulator therapy available to more patients and with increasing pregnancies in individuals with CF, there is a growing need to understand the effects of these agents during pregnancy. There are few reports of their continued use in the literature, although it is likely that this is not an uncommon occurrence. We report the uncomplicated and successful pregnancy of a woman treated with lumacaftor/ivacaftor, as well as the clinical course of the infant during the first 9 months of life. We also report drug levels in plasma from the mother, cord blood, breast milk, and infant to estimate fetal and infant drug exposure

Cauchy's infinitesimals, his sum theorem, and foundational paradigms

Cauchy's sum theorem is a prototype of what is today a basic result on the convergence of a series of functions in undergraduate analysis. We seek to interpret Cauchy's proof, and discuss the related epistemological questions involved in comparing distinct interpretive paradigms. Cauchy's proof is often interpreted in the modern framework of a Weierstrassian paradigm. We analyze Cauchy's proof closely and show that it finds closer proxies in a different modern framework. Keywords: Cauchy's infinitesimal; sum theorem; quantifier alternation; uniform convergence; foundational paradigms.Comment: 42 pages; to appear in Foundations of Scienc

Beam Energy Dependence of the Third Harmonic of Azimuthal Correlations in Au+Au Collisions at RHIC

We present results from a harmonic decomposition of two-particle azimuthal correlations measured with the STAR detector in Au+Au collisions for energies ranging from $\sqrt{s_{NN}}=7.7$ GeV to 200 GeV. The third harmonic $v_3^2\{2\}=\langle \cos3(\phi_1-\phi_2)\rangle$, where $\phi_1-\phi_2$ is the angular difference in azimuth, is studied as a function of the pseudorapidity difference between particle pairs $\Delta\eta = \eta_1-\eta_2$. Non-zero {\vthree} is directly related to the previously observed large-$\Delta\eta$ narrow-$\Delta\phi$ ridge correlations and has been shown in models to be sensitive to the existence of a low viscosity Quark Gluon Plasma (QGP) phase. For sufficiently central collisions, $v_3^2\{2\}$ persist down to an energy of 7.7 GeV suggesting that QGP may be created even in these low energy collisions. In peripheral collisions at these low energies however, $v_3^2\{2\}$ is consistent with zero. When scaled by pseudorapidity density of charged particle multiplicity per participating nucleon pair, $v_3^2\{2\}$ for central collisions shows a minimum near {\snn}$=20$ GeV.Comment: 7 pages, 4 figures, for submission to Phys. Rev. Let

J/ψ\rm{J}/\psi production at low transverse momentum in p+p and d+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

We report on the measurement of $\rm{J}/\psi$ production in the dielectron channel at mid-rapidity (|y|<1) in p+p and d+Au collisions at $\sqrt{s_{NN}}$ = 200 GeV from the STAR experiment at the Relativistic Heavy Ion Collider. The transverse momentum $p_{T}$ spectra in p+p for $p_{T}$ < 4 GeV/c and d+Au collisions for $p_{T}$ < 3 GeV/c are presented. These measurements extend the STAR coverage for $\rm{J}/\psi$ production in p+p collisions to low $p_{T}$. The $$ from the measured $\rm{J}/\psi$ invariant cross section in p+p and d+Au collisions are evaluated and compared to similar measurements at other collision energies. The nuclear modification factor for $\rm{J}/\psi$ is extracted as a function of $p_{T}$ and collision centrality in d+Au and compared to model calculations using the modified nuclear Parton Distribution Function and a final-state $\rm{J}/\psi$ nuclear absorption cross section

A standardisation framework for bio‐logging data to advance ecological research and conservation

Bio‐logging data obtained by tagging animals are key to addressing global conservation challenges. However, the many thousands of existing bio‐logging datasets are not easily discoverable, universally comparable, nor readily accessible through existing repositories and across platforms, slowing down ecological research and effective management. A set of universal standards is needed to ensure discoverability, interoperability and effective translation of bio‐logging data into research and management recommendations. We propose a standardisation framework adhering to existing data principles (FAIR: Findable, Accessible, Interoperable and Reusable; and TRUST: Transparency, Responsibility, User focus, Sustainability and Technology) and involving the use of simple templates to create a data flow from manufacturers and researchers to compliant repositories, where automated procedures should be in place to prepare data availability into four standardised levels: (a) decoded raw data, (b) curated data, (c) interpolated data and (d) gridded data. Our framework allows for integration of simple tabular arrays (e.g. csv files) and creation of sharable and interoperable network Common Data Form (netCDF) files containing all the needed information for accuracy‐of‐use, rightful attribution (ensuring data providers keep ownership through the entire process) and data preservation security. We show the standardisation benefits for all stakeholders involved, and illustrate the application of our framework by focusing on marine animals and by providing examples of the workflow across all data levels, including filled templates and code to process data between levels, as well as templates to prepare netCDF files ready for sharing. Adoption of our framework will facilitate collection of Essential Ocean Variables (EOVs) in support of the Global Ocean Observing System (GOOS) and inter‐governmental assessments (e.g. the World Ocean Assessment), and will provide a starting point for broader efforts to establish interoperable bio‐logging data formats across all fields in animal ecology

Thermal stratification drives movement of a coastal apex predator

A characterization of the thermal ecology of fishes is needed to better understand changes in ecosystems and species distributions arising from global warming. The movement of wild animals during changing environmental conditions provides essential information to help predict the future thermal response of large marine predators. We used acoustic telemetry to monitor the vertical movement activity of the common dentex (Dentex dentex), a Mediterranean coastal predator, in relation to the oscillations of the seasonal thermocline during two summer periods in the Medes Islands marine reserve (NW Mediterranean Sea). During the summer stratification period, the common dentex presented a clear preference for the warm suprathermoclinal layer, and adjusted their vertical movements following the depth changes of the thermocline. The same preference was also observed during the night, when fish were less active. Due to this behaviour, we hypothesize that inter-annual thermal oscillations and the predicted lengthening of summer conditions will have a significant positive impact on the metabolic efficiency, activity levels, and population dynamics of this species, particularly in its northern limit of distribution. These changes in the dynamics of an ecosystem’s keystone predator might cascade down to lower trophic levels, potentially re-defining the coastal fish communities of the futureVersión del editor2,92

Effects of Alcohol on the Acquisition and Expression of Fear Potentiated Startle in Mouse Lines Selectively Bred for High and Low Alcohol Preference

Rationale: Anxiety disorders and alcohol-use disorders frequently co-occur in humans perhaps because alcohol relieves anxiety. Studies in humans and rats indicate that alcohol may have greater anxiolytic effects in organisms with increased genetic propensity for high alcohol consumption. Objectives and Methods: The purpose of this study was to investigate the effects of moderate doses of alcohol (0.5, 1.0, 1.5 g/kg) on the acquisition and expression of anxiety-related behavior using a fear-potentiated startle (FPS) procedure. Experiments were conducted in two replicate pairs of mouse lines selectively bred for high- (HAP1 and HAP2) and low- (LAP1 and LAP2) alcohol preference; these lines have previously shown a genetic correlation between alcohol preference and FPS (HAP\u3eLAP; Barrenha and Chester 2007). In a control experiment, the effect of diazepam (4.0 mg/kg) on the expression of FPS was tested in HAP2 and LAP2 mice. Results: The 1.5 g/kg alcohol dose moderately decreased the expression of FPS in both HAP lines but not LAP lines. Alcohol had no effect on the acquisition of FPS in any line. Diazepam reduced FPS to a similar extent in both HAP2 and LAP2 mice. Conclusions: HAP mice may be more sensitive to the anxiolytic effects of alcohol than LAP mice when alcohol is given prior to the expression of FPS. These data collected in two pairs of HAP/LAP mouse lines suggest that the anxiolytic response to alcohol in HAP mice may be genetically correlated with their propensity toward high alcohol preference and robust FPS