5,714 research outputs found

    The clinical development of the somatostatin analogue octreotide

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    The clinical development of the somatostatin analogue octreotide

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    The impact of consent on observational research: a comparison of outcomes from consenters and non consenters to an observational study

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    Background Public health benefits from research often rely on the use of data from personal medical records. When neither patient consent nor anonymisation is possible, the case for accessing such records for research purposes depends on an assessment of the probabilities of public benefit and individual harm. Methods In the late 1990s, we carried out an observational study which compared the care given to affluent and deprived women with breast cancer. Patient consent was not required at that time for review of medical records, but was obtained later in the process prior to participation in the questionnaire study. We have re-analysed our original results to compare the whole sample with those who later provided consent. Results Two important findings emerged from the re-analysis of our data which if presented initially would have resulted in insufficient and inaccurate reporting. Firstly, the reduced dataset contains no information about women presenting with locally advanced or metastatic cancer and we would have been unable to demonstrate one of our initial key findings: namely a larger number of such women in the deprived group. Secondly, our re-analysis of the consented women shows that significantly more women from deprived areas (51 v 31%, p = 0.018) received radiotherapy compared to women from more affluent areas. Previously published data from the entire sample demonstrated no difference in radiotherapy treatment between the affluent and deprived groups. Conclusion The risk benefit assessment made regarding the use of medical records without consent should include the benefits of obtaining research evidence based on 100% of the population and the possibility of inappropriate or insufficient findings if research is confined to consented populations

    Temporal estimation in prediction motion tasks is biased by a moving destination

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    © 2018 The Authors. An ability to predict the time-to-contact (TTC) of moving objects that become momentarily hidden is advantageous in everyday life and could be particularly so in fast-ball sports. Prediction motion (PM) experiments have sought to test this ability using tasks where a disappearing target moves toward a stationary destination. Here, we developed two novel versions of the PM task in which the destination either moved away from (Chase) or toward (Attract) the moving target. The target and destination moved with different speeds such that collision occurred 750, 1,000 or 1,250 ms after target occlusion. To determine if domain-specific experience conveys an advantage in PM tasks, we compared the performance of different sporting groups ranging from internationally competing athletes to nonsporting controls. There was no difference in performance between sporting groups and non-sporting controls but there were significant and independent effects on response error by target speed, destination speed, and occlusion period. We simulated these findings using a revised version of the linear TTC model of response timing for PM tasks (Yakimoff, Bocheva, & Mitrania, 1987; Yakimoff, Mateeff, Ehrenstein, & Hohnsbein, 1993) in which retinal input from the moving destination biases the internal representation of the occluded target. This revision closely reproduced the observed patterns of response error and thus describes a means by which the brain might estimate TTC when the target and destination are in motion

    Mangarara Formation: exhumed remnants of a middle Miocene, temperate carbonate, submarine channel-fan system on the eastern margin of Taranaki Basin, New Zealand

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    The middle Miocene Mangarara Formation is a thin (1–60 m), laterally discontinuous unit of moderately to highly calcareous (40–90%) facies of sandy to pure limestone, bioclastic sandstone, and conglomerate that crops out in a few valleys in North Taranaki across the transition from King Country Basin into offshore Taranaki Basin. The unit occurs within hemipelagic (slope) mudstone of Manganui Formation, is stratigraphically associated with redeposited sandstone of Moki Formation, and is overlain by redeposited volcaniclastic sandstone of Mohakatino Formation. The calcareous facies of the Mangarara Formation are interpreted to be mainly mass-emplaced deposits having channelised and sheet-like geometries, sedimentary structures supportive of redeposition, mixed environment fossil associations, and stratigraphic enclosure within bathyal mudrocks and flysch. The carbonate component of the deposits consists mainly of bivalves, larger benthic foraminifers (especially Amphistegina), coralline red algae including rhodoliths (Lithothamnion and Mesophyllum), and bryozoans, a warm-temperate, shallow marine skeletal association. While sediment derivation was partly from an eastern contemporary shelf, the bulk of the skeletal carbonate is inferred to have been sourced from shoal carbonate factories around and upon isolated basement highs (Patea-Tongaporutu High) to the south. The Mangarara sediments were redeposited within slope gullies and broad open submarine channels and lobes in the vicinity of the channel-lobe transition zone of a submarine fan system. Different phases of sediment transport and deposition (lateral-accretion and aggradation stages) are identified in the channel infilling. Dual fan systems likely co-existed, one dominating and predominantly siliciclastic in nature (Moki Formation), and the other infrequent and involving the temperate calcareous deposits of Mangarara Formation. The Mangarara Formation is an outcrop analogue for middle Miocene-age carbonate slope-fan deposits elsewhere in subsurface Taranaki Basin, New Zealand

    Electro-fluid dynamics of aqueous humor production: simulations and new directions.

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    Purpose: to theoretically investigate the role of bicarbonate ion (HCO− 3 ) on the nonpigmented transepithelial potential di erence Vm, the sodium potassium pump (Na/K) and the active secretion of aqueous humor. Methods: a three-dimensional mathematical model is proposed to isolate the roles of HCO− 3 and Na+, which are di icult to investigate experimentally. The model combines the velocity-extended Poisson-Nernst-Planck equations to describe ion electrodi usion and the Stokes equations to describe aqueous humor flow into the basolateral space adjacent to the nonpigmented ephitelial cells. Results: Computations show that Vm is close to baseline experimental measurements (on monkeys) in the range [−2.7, −2.3]mV only if HCO− 3 is included in the simulation. The model is also capable of reproducing the flow of Na+ exiting the cell and the flow of K+ entering the cell, in accordance with the physiology of the Na/K pump. The simulated Na/K ratio is 1.53, which is in very good agreement with the theoretical value of 1.5. Conclusion: Model simulations suggest that HCO− 3 inhibition may prevent physiologically correct baseline values of the nonpigmented transepithelial potential di erence and Na/K ATPase function. This may provide useful indication in the design of medications that decrease the active secretion of aqueous humor, and supports the advantage of using mathematical models as a noninvasive complement of animal models

    Vanishing of phase coherence in underdoped Bi_2Sr_2CaCu_2O_8+d

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    Coherent time-domain spectroscopy is used to measure the screening and dissipation of high-frequency electromagnetic fields in a set of underdoped Bi_2Sr_2CaCu_2O_8+d thin films. The measurements provide direct evidence for a phase-fluctuation driven transition from the superconductor to normal state, with dynamics described well by the Berezinskii-Kosterlitz-Thouless theory of vortex-pair unbinding.Comment: Nature, Vol. 398, 18 March 1999, pg. 221 4 pages with 4 included figure

    Saddle point localization of molecular wavefunctions

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    The quantum mechanical description of isomerization is based on bound eigenstates of the molecular potential energy surface. For the near-minimum regions there is a textbook-based relationship between the potential and eigenenergies. Here we show how the saddle point region that connects the two minima is encoded in the eigenstates of the model quartic potential and in the energy levels of the [H, C, N] potential energy surface. We model the spacing of the eigenenergies with the energy dependent classical oscillation frequency decreasing to zero at the saddle point. The eigenstates with the smallest spacing are localized at the saddle point. The analysis of the HCN???HNC isomerization states shows that the eigenstates with small energy spacing relative to the effective (v1, v3, l) bending potentials are highly localized in the bending coordinate at the transition state. These spectroscopically detectable states represent a chemical marker of the transition state in the eigenenergy spectrum. The method developed here provides a basis for modeling characteristic patterns in the eigenenergy spectrum of bound states
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