Initiation and maintenance of swimming in hatchling xenopus laevis tadpoles

Effective movement is central to survival and it is essential for all animals to react in response to changes around them. In many animals the rhythmic signals that drive locomotion are generated intrinsically by small networks of neurons in the nervous system which can be switched on and off. In this thesis I use a very simple animal, in which the behaviours and neuronal networks have been well characterised experimentally, to explore the salient features of such networks. Two days after hatching, tadpoles of the frog Xenopus laevis respond to a brief touch to the head by starting to swim. The swimming rhythm is driven by a small population of electrically coupled brainstem neurons (called dINs) on each side of the tadpole. These neurons also receive synaptic input following head skin stimulation. I build biophysical computational models of these neurons based on experimental data in order to address questions about the effects of electrical coupling, synaptic feedback excitation and initiation pathways. My aim is better understanding of how swimming activity is initiated and sustained in the tadpole. I find that the electrical coupling between the dINs causes their firing properties to be modulated. This allows two experimental observations to be reconciled: that a dIN only fires a single action potential in response to step current injections but the population fires like pacemakers during swimming. I build on this hypothesis and show that long-lasting, excitatory feedback within the population of dINs allows rhythmic pacemaker activity to be sustained in one side of the nervous system. This activity can be switched on and off at short latency in response to biologically realistic synaptic input. I further investigate models of synaptic input from a defined swim initiation pathway and show that electrical coupling causes a population of dINs to be recruited to fire either as a group or not at all. This allows the animal to convert continuously varying sensory stimuli into a discrete decision. Finally I find that it is difficult to reliably start swimming-like activity in the tadpole model using simple, short-latency, symmetrical initiation pathways but that by using more complex, asymmetrical, neuronal-pathways to each side of the body, consistent with experimental observations, the initiation of swimming is more robust. Throughout this work, I make testable predictions about the population of brainstem neurons and also describe where more experimental data is needed. In order to manage the parameters and simulations, I present prototype libraries to build and manage these biophysical model networks

Biogeochemical significance of pelagic ecosystem function:An end-cretaceous case study

This work was aided by a Nuffield Summer Studentship granted to MJH, a U.S. Science Support Program (USSSP) Post-Expedition Activity award for IODP Exp. 342 to PMH, a Flint Postdoctoral Fellowship to DEP, a NERC PhD Studentship granted to JWBR, and a URF and Wolfson merit award to DNS.Pelagic ecosystem function is integral to global biogeochemical cycling, and plays a major role in modulating atmospheric CO2 concentrations (pCO2). Uncertainty as to the effects of human activities on marine ecosystem function hinders projection of future atmospheric pCO2. To this end, events in the geological past can provide informative case studies in the response of ecosystem function to environmental and ecological changes. Around the Cretaceous–Palaeogene (K–Pg) boundary, two such events occurred: Deccan large igneous province (LIP) eruptions and massive bolide impact at the Yucatan Peninsula. Both perturbed the environment, but only the impact coincided with marine mass extinction. As such, we use these events to directly contrast the response of marine biogeochemical cycling to environmental perturbation with and without changes in global species richness. We measure this biogeochemical response using records of deep-sea carbonate preservation. We find that Late Cretaceous Deccan volcanism prompted transient deep-sea carbonate dissolution of a larger magnitude and timescale than predicted by geochemical models. Even so, the effect of volcanism on carbonate preservation was slight compared with bolide impact. Empirical records and geochemical models support a pronounced increase in carbonate saturation state for more than 500 000 years following the mass extinction of pelagic carbonate producers at the K–Pg boundary. These examples highlight the importance of pelagic ecosystems in moderating climate and ocean chemistry.PostprintPeer reviewe

Detection and diagnosis of large airway collapse: a systematic review

Large airway collapse (LAC) is a frequently encountered clinical problem, caused by tracheobronchomalacia +/− excessive dynamic airway collapse, yet there are currently no universally accepted diagnostic criteria. We systematically reviewed studies reporting a diagnostic approach to LAC in healthy adults and patients, to compare diagnostic modalities and criteria used. Electronic databases were searched for relevant studies between 1989 and 2019. Studies that reported a diagnostic approach using computed tomography (CT), magnetic resonance imaging or flexible fibreoptic bronchoscopy were included. Random effects meta-analyses were performed to estimate the prevalence of LAC in healthy subjects and in patients with chronic obstructive airway diseases. We included 41 studies, describing 10 071 subjects (47% female) with a mean±sd age of 59±9 years. Most studies (n=35) reported CT findings, and only three studies reported bronchoscopic findings. The most reported diagnostic criterion was a ≥50% reduction in tracheal or main bronchi calibre at end-expiration on dynamic expiratory CT. Meta-analyses of relevant studies found that 17% (95% CI: 0–61%) of healthy subjects and 27% (95% CI: 11–46%) of patients with chronic airways disease were classified as having LAC, using this threshold. The most reported approach to diagnose LAC utilises CT diagnostics, and at a threshold used by most clinicians (i.e.≥50%) may classify a considerable proportion of healthy individuals as being abnormal and having LAC in a quarter of patients with chronic airways disease. Future work should focus on establishing more precise diagnostic criteria for LAC, relating this to relevant physiological and disease sequelae

Detection and diagnosis of large airway collapse: a systematic review

Large airway collapse (LAC) is a frequently encountered clinical problem, caused by tracheobronchomalacia +/− excessive dynamic airway collapse, yet there are currently no universally accepted diagnostic criteria. We systematically reviewed studies reporting a diagnostic approach to LAC in healthy adults and patients, to compare diagnostic modalities and criteria used. Electronic databases were searched for relevant studies between 1989 and 2019. Studies that reported a diagnostic approach using computed tomography (CT), magnetic resonance imaging or flexible fibreoptic bronchoscopy were included. Random effects meta-analyses were performed to estimate the prevalence of LAC in healthy subjects and in patients with chronic obstructive airway diseases. We included 41 studies, describing 10 071 subjects (47% female) with a mean±sd age of 59±9 years. Most studies (n=35) reported CT findings, and only three studies reported bronchoscopic findings. The most reported diagnostic criterion was a ≥50% reduction in tracheal or main bronchi calibre at end-expiration on dynamic expiratory CT. Meta-analyses of relevant studies found that 17% (95% CI: 0–61%) of healthy subjects and 27% (95% CI: 11–46%) of patients with chronic airways disease were classified as having LAC, using this threshold. The most reported approach to diagnose LAC utilises CT diagnostics, and at a threshold used by most clinicians (i.e.≥50%) may classify a considerable proportion of healthy individuals as being abnormal and having LAC in a quarter of patients with chronic airways disease. Future work should focus on establishing more precise diagnostic criteria for LAC, relating this to relevant physiological and disease sequelae

Designing for designers: Towards the development of accessible ICT products and services using the VERITAS framework

Among key design practices which contribute to the development of inclusive ICT products and services is user testing with people with disabilities. Traditionally, this involves partial or minimal user testing through the usage of standard heuristics, employing external assisting devices, and the direct feedback of impaired users. However, efficiency could be improved if designers could readily analyse the needs of their target audience. The VERITAS framework simulates and systematically analyses how users with various impairments interact with the use of ICT products and services. Findings show that the VERITAS framework is useful to designers, offering an intuitive approach to inclusive design.The work presented in this article forms part of VERITAS, which is funded by the European Commission's 7th Framework Programme (FP7) (grant agreement # 247765 FP7-ICT-2009.7.2)

Weak Lensing with SDSS Commissioning Data: The Galaxy-Mass Correlation Function To 1/h Mpc

(abridged) We present measurements of galaxy-galaxy lensing from early commissioning imaging data from the Sloan Digital Sky Survey (SDSS). We measure a mean tangential shear around a stacked sample of foreground galaxies in three bandpasses out to angular radii of 600'', detecting the shear signal at very high statistical significance. The shear profile is well described by a power-law. A variety of rigorous tests demonstrate the reality of the gravitational lensing signal and confirm the uncertainty estimates. We interpret our results by modeling the mass distributions of the foreground galaxies as approximately isothermal spheres characterized by a velocity dispersion and a truncation radius. The velocity dispersion is constrained to be 150-190 km/s at 95% confidence (145-195 km/s including systematic uncertainties), consistent with previous determinations but with smaller error bars. Our detection of shear at large angular radii sets a 95% confidence lower limit $s>140^{\prime\prime}$, corresponding to a physical radius of $260h^{-1}$ kpc, implying that galaxy halos extend to very large radii. However, it is likely that this is being biased high by diffuse matter in the halos of groups and clusters. We also present a preliminary determination of the galaxy-mass correlation function finding a correlation length similar to the galaxy autocorrelation function and consistency with a low matter density universe with modest bias. The full SDSS will cover an area 44 times larger and provide spectroscopic redshifts for the foreground galaxies, making it possible to greatly improve the precision of these constraints, measure additional parameters such as halo shape, and measure the properties of dark matter halos separately for many different classes of galaxies.Comment: 28 pages, 11 figures, submitted to A

d-Dimer elevation and adverse outcomes

d-Dimer is a biomarker of fibrin formation and degradation. While a d-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated d-dimer with adverse outcomes has received far less emphasis. An elevated d-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated d-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the d-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted

The Multi-Object, Fiber-Fed Spectrographs for SDSS and the Baryon Oscillation Spectroscopic Survey

We present the design and performance of the multi-object fiber spectrographs for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon Oscillation Spectroscopic Survey (BOSS). Originally commissioned in Fall 1999 on the 2.5-m aperture Sloan Telescope at Apache Point Observatory, the spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II surveys, enabling a wide variety of Galactic and extra-galactic science including the first observation of baryon acoustic oscillations in 2005. The spectrographs were upgraded in 2009 and are currently in use for BOSS, the flagship survey of the third-generation SDSS-III project. BOSS will measure redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyman-alpha absorption of 160,000 high redshift quasars over 10,000 square degrees of sky, making percent level measurements of the absolute cosmic distance scale of the Universe and placing tight constraints on the equation of state of dark energy. The twin multi-object fiber spectrographs utilize a simple optical layout with reflective collimators, gratings, all-refractive cameras, and state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in two channels over a bandpass covering the near ultraviolet to the near infrared, with a resolving power R = \lambda/FWHM ~ 2000. Building on proven heritage, the spectrographs were upgraded for BOSS with volume-phase holographic gratings and modern CCD detectors, improving the peak throughput by nearly a factor of two, extending the bandpass to cover 360 < \lambda < 1000 nm, and increasing the number of fibers from 640 to 1000 per exposure. In this paper we describe the original SDSS spectrograph design and the upgrades implemented for BOSS, and document the predicted and measured performances.Comment: 43 pages, 42 figures, revised according to referee report and accepted by AJ. Provides background for the instrument responsible for SDSS and BOSS spectra. 4th in a series of survey technical papers released in Summer 2012, including arXiv:1207.7137 (DR9), arXiv:1207.7326 (Spectral Classification), and arXiv:1208.0022 (BOSS Overview

Rapid ocean acidification and protracted Earth system recovery followed the end-Cretaceous Chicxulub impact

J.W.B.R. was supported by ERC Starting Grant 805246 OldCO2NewArchives.Mass extinction at the Cretaceous–Paleogene (K-Pg) boundary coincides with the Chicxulub bolide impact and also falls within the broader time frame of Deccan trap emplacement. Critically, though, empirical evidence as to how either of these factors could have driven observed extinction patterns and carbon cycle perturbations is still lacking. Here, using boron isotopes in foraminifera, we document a geologically rapid surface-ocean pH drop following the Chicxulub impact, supporting impact-induced ocean acidification as a mechanism for ecological collapse in the marine realm. Subsequently, surface water pH rebounded sharply with the extinction of marine calcifiers and the associated imbalance in the global carbon cycle. Our reconstructed water-column pH gradients, combined with Earth system modeling, indicate that a partial ∼50% reduction in global marine primary productivity is sufficient to explain observed marine carbon isotope patterns at the K-Pg, due to the underlying action of the solubility pump. While primary productivity recovered within a few tens of thousands of years, inefficiency in carbon export to the deep sea lasted much longer. This phased recovery scenario reconciles competing hypotheses previously put forward to explain the K-Pg carbon isotope records, and explains both spatially variable patterns of change in marine productivity across the event and a lack of extinction at the deep sea floor. In sum, we provide insights into the drivers of the last mass extinction, the recovery of marine carbon cycling in a postextinction world, and the way in which marine life imprints its isotopic signal onto the geological record.Publisher PDFPeer reviewe