Partially linear censored quantile regression

Censored regression quantile (CRQ) methods provide a powerful and flexible approach to the analysis of censored survival data when standard linear models are felt to be appropriate. In many cases however, greater flexibility is desired to go beyond the usual multiple regression paradigm. One area of common interest is that of partially linear models: one (or more) of the explanatory covariates are assumed to act on the response through a non-linear function. Here the CRQ approach of Portnoy (J Am Stat Assoc 98:1001–1012, 2003) is extended to this partially linear setting. Basic consistency results are presented. A simulation experiment and unemployment example justify the value of the partially linear approach over methods based on the Cox proportional hazards model and on methods not permitting nonlinearity

Smallanthus macroscyphus: a new source of antidiabetic compounds

The aim of the present study was to analyze the in vivo hypoglycaemic effects of both decoction of Smallanthus macroscyphus leaves and pure crystalline polymatin A isolated from its leaves. Phytochemical analysis of the leaf decoction showed that its major constituents were caffeic, chlorogenic and three dicaffeoilquinic acids, together with the sesquiterpene lactone polymatin A. Oral glucose tolerance test in normal rats was performed to evaluate the hypoglycemic activity and to choose the minimum effective dose of the decoction and polymatin A. They have effective hypoglycemic activity at the minimum dose of 140 mg dry extract and 14 mg crystalline powder/kg body weight, respectively, and were selected for the following experiments. Oral administration of a single-dose of decoction produced a moderate lowering effect in fasting glycemia of normal rats, whereas polymatin A had no significant effect. We also assessed the effect of a single-dose on post-prandial blood glucose, resulting in an inhibition of the hyperglycemic peak after sucrose overload. Daily administration of decoction or polymatin A for 4 weeks produced an effective glycemic control in diabetic animals, with a decrease in urinary glucose excretion and a significant reduction in the HbA1c levels. Although there were no significant increases in plasma insulin levels, both treatments improved the fasting blood glucose/insulin ratio. In vivo acute toxicity studies were performed in adult Wistar rats. There were no deaths or signs of toxicity observed after oral administration of decoction or polymatin A at any dose level up to the highest dose tested (14.0 g /kg and 2.8 g /kg, respectively). The results presented here strongly support the notion that S. macroscyphus represents a new source of antidiabetic compounds that could help to manage diabetes more efficiently and safely.Fil: Serra Barcellona, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Coll Araoz, Maria Victoria. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Ecología Regional; ArgentinaFil: Cabrera, Wilfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Habib, Natalia Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Honore, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Catalan, Cesar Atilio Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto de Quimica del Noroeste; ArgentinaFil: Grau, Alfredo. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Ecología Regional; ArgentinaFil: Genta, Susana B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

The lady vanishes: what's missing from the stem cell debate

Most opponents of somatic cell nuclear transfer and embryonic stem cell technologies base their arguments on the twin assertions that the embryo is either a human being or a potential human being, and that it is wrong to destroy a human being or potential human being in order to produce stem cell lines. Proponents’ justifications of stem cell research are more varied, but not enough to escape the charge of obsession with the status of the embryo. What unites the two warring sides in ‘the stem cell wars’ is that women are equally invisible to both: ‘the lady vanishes’. Yet the only legitimate property in the body is that which women possess in their reproductive tissue and the products of their reproductive labour. By drawing on the accepted characterisation in law of property as a bundle of rights, and on a Hegelian model of contract as mutual recognition, we can lessen the impact of the tendency to regard women and their eggs as merely receptacles and women’s reproductive labour as unimportant

Increased function of pronociceptive TRPV1 at the level of the joint in a rat model of osteoarthritis pain

Objectives Blockade of transient receptor potential vanilloid 1 (TRPV1) with systemic antagonists attenuates osteoarthritis (OA) pain behaviour in rat models, but on-target-mediated hyperthermia has halted clinical trials. The present study investigated the potential for targeting TRPV1 receptors within the OA joint in order to produce analgesia. Methods The presence of TRPV1 receptors in human synovium was detected using western blotting and immunohistochemistry. In a rat model of OA, joint levels of an endogenous ligand for TRPV1, 12- ydroxyeicosatetraenoic acid (12-HETE), were quantified using liquid chromatography-tandem mass spectrometry (LCMS/MS). Effects of peripheral administration of the TRPV1 receptor antagonist JNJ-17203212 on afferent fibre activity, pain behaviour and core body temperature were investigated. Effects of a spinal administration of JNJ-17203212 on dorsal horn neuronal responses were studied. Results We demonstrate increased TRPV1 immunoreactivity in human OA synovium, confirming the diseased joint as a potential therapeutic target for TRPV1-mediated analgesia. In a model of OA pain, we report increased joint levels of 12-HETE, and the sensitisation of joint afferent neurones to mechanical stimulation of the knee. Local administration of JNJ- 17203212 reversed this sensitisation of joint afferents and inhibited pain behaviour (weight-bearing asymmetry), to a comparable extent as systemic JNJ- 17203212, in this model of OA pain, but did not alter core body temperature. There was no evidence for increased TRPV1 function in the spinal cord in this model of OA pain. Conclusions Our data provide a clinical and mechanistic rationale for the future investigation of the therapeutic benefits of intra-articular administration of TRPV1 antagonists for the treatment of OA pain

Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

BACKGROUND: Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure. METHODS AND RESULTS: MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3. CONCLUSIONS: This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

GATE : a simulation toolkit for PET and SPECT

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols, and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at the address http://www-lphe.epfl.ch/GATE/

A New Model for Interdependent Durations

This paper introduces a bivariate version of the generalized accelerated failure time model. It allows for simultaneity in the econometric sense that the two realized outcomes depend structurally on each other. Another feature of the proposed model is that it will generate equal durations with positive probability. Our approach takes a stylized economic model that leads to a univariate generalized accelerated failure time model as a starting point. In this model, agents decide when to transition from an initial state to a new one, and the covariates influence the difference in the utility flow in the two states. We introduce simultaneity by allowing the utility flow to depend on the status of the other person. The econometric model is then completed by assuming that the observed outcome is the Nash bargaining solution in that simple economic model. The advantage of this approach is that it includes independent realizations from the generalized accelerated failure time model as a special case, and deviations from this special case can be given an economic interpretation. We established identification under assumptions that are similar to those in the literature on nonparametric estimation of duration models. We illustrate the model by studying the joint retirement decisions in married couples using the Health and Retirement Study. In that example, it seems reasonable to allow for the possibility that each partner’s optimal retirement time depends on the retirement time of the spouse. Moreover, the data suggest that the wife and the husband retire at the same time for a nonnegligible fraction of couples. The main empirical finding is that the simultaneity is economically important. In our preferred specification, the indirect utility associated with being retired increases by approximately 5% when one’s spouse retires

Autoradiographic Characterization and Localization of Quisqualate Binding Sites in Rat Brain Using the Antagonist [ 3 H]6-Cyano-7-Nitroquinoxaline-2,3-Dione: Comparison with ( R,S )-[ 3 H]Α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Binding Sites

Using quantitative autoradiography, we have investigated the binding sites for the potent competitive non- N -methyl-D-aspartate (non-NMDA) glutamate receptor antagonist [ 3 H]6-cyano-7-nitro-quinoxaline-2,3-dione ([ 3 H]-CNQX) in rat brain sections. [ 3 H]CNQX binding was regionally distributed, with the highest levels of binding present in hippocampus in the stratum radiatum of CA1, stratum lucidum of CA3, and molecular layer of dentate gyrus. Scatchard analysis of [ 3 H]CNQX binding in the cerebellar molecular layer revealed an apparent single binding site with a K D = 67 ± 9.0 n M and B max = 3.56 ± 0.34 pmol/mg protein. In displacement studies, quisqualate, L-glutamate, and kainate also appeared to bind to a single class of sites. However, ( R,S )- Α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) displacement of [ 3 H]CNQX binding revealed two binding sites in the cerebellar molecular layer. Binding of [ 3 H]AMPA to quisqualate receptors in the presence of potassium thiocyanate produced curvilinear Scatchard plots. The curves could be resolved into two binding sites with K D1 = 9.0 ± 3.5 n M , B max = 0.15 ± 0.05 pmol/mg protein, K D2 = 278 ± 50 n M , and B max = 1.54 ± 0.20 pmol/mg protein. The heterogeneous anatomical distribution of [ 3 H]CNQX binding sites correlated to the binding of L-[ 3 H]glutamate to quisqualate receptors and to sites labeled with [ 3 H]AMPA. These results suggest that the non-NMDA glutamate receptor antagonist [ 3 H]CNQX binds with equal affinity to two states of quisqualate receptors which have different affinities for the agonist [ 3 H]AMPA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65634/1/j.1471-4159.1990.tb01925.x.pd

Close encounters of a critical kind: a diffractive musing in/between new material feminism and object-oriented ontology

For a number of years, new material feminists have been developing new theoretical tools, new modes of conceptual analysis and new ethical frameworks. Object-oriented ontology, part of the speculative realism ‘movement’, has been engaged in something similar. Yet these endeavours have often taken place in ‘parallel universes’, despite sharing – or at least colliding around – a range of somewhat similar ontological and epistemological commitments. Composed as a diffractive musing encounter in which insights are read ‘through one another’ (Barad, 2007: 25) in order to ‘attend to … details and specificities of relations of difference and how they matter’ (Barad, 2007:71), the article brings Barad’s Meeting the Universe Halfway, already a ‘foundational’ text for new material feminism, into an encounter with a speculative realist text of the same ‘foundational’ status, Harman’s The Quadruple Object. The article develops a notion of diffractive musing as embodied, sensory struggle which instantiates intellectual generosity as a mode of critique. Following this, it puts diffractive musing to work theoretically via an encounter between object-oriented ontology and new material feminism. Keywords : new material feminism, speculative realism, diffraction, musing, critiqu