Comparisons of Hyv\"arinen and pairwise estimators in two simple linear time series models

The aim of this paper is to compare numerically the performance of two estimators based on Hyv\"arinen's local homogeneous scoring rule with that of the full and the pairwise maximum likelihood estimators. In particular, two different model settings, for which both full and pairwise maximum likelihood estimators can be obtained, have been considered: the first order autoregressive model (AR(1)) and the moving average model (MA(1)). Simulation studies highlight very different behaviours for the Hyv\"arinen scoring rule estimators relative to the pairwise likelihood estimators in these two settings.Comment: 14 pages, 2 figure

High frequency of inadequate test requests for antiphospholipid antibodies in daily clinical practice

Abstract Background: We have empirically noted that many physicians routinely request anti-phospholipid antibodies (aPL) without a correct clinical indication. The aim of this study was to evaluate retrospectively whether aPL testing at our Thrombosis Centre was justified. Methods: Medical records from 520 subjects for aPL screening tests for various clinical conditions were reviewed. The aPL screening tests were: lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) and anti-β(2) glycoptotein I (aβ(2) GPI). Requests for aPL screening were divided into justified, potentially justified or not adequately justified. Results: aPL testing requests were considered justified in 358 (69%) patients, potentially justified in 66 (12.6%) and not adequately justified in 96 (18.4%). LA was positive in 65 (18%) of justified requests and in only one (1%) of the 96 potentially justified requests. None of the 66 not adequately justified for aPL testing was positive for LA. aβ(2) ..

Synchronized network activity in developing rat hippocampus involves regional hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function.

The principal form of synchronized network activity in neonatal hippocampus consists of low frequency 'giant depolarizing potentials' (GDPs). Whereas contribution of both GABA and glutamate to their generation has been demonstrated, full understanding of the mechanisms underlying these synchronized activity bursts remains incomplete. A contribution of the h-current, conducted by HCN channels, to GDPs has been a topic of substantial interest. Here we focus on HCN1, the prevalent HCN channel isoform in neonatal hippocampus, and demonstrate an HCN1 spatiotemporal expression pattern in both CA3 principal cells and interneurons that correlates with the developmental profile of GDPs. Abrogation of HCN physiological function in CA3, via the selective I(h)-blocker ZD7288, disrupts GDP generation. Furthermore, ZD7288 specifically abolishes spontaneous bursting of the CA3 pyramidal cells at frequencies typical of GDPs without major influence on interneuronal firing. These findings support a pivotal role for HCN channels expressed by CA3 neurons, and particularly CA3 pyramidal cells, in GDP-related network synchronization

Fluid-flow pressure measurements and thermo-fluid characterization of a single loop two-phase passive heat transfer device

Abstract A Novel Single Loop Pulsating Heat Pipe (SLPHP), with an inner diameter of 2 mm, filled up with two working fluids (Ethanol and FC-72, Filling Ratio of 60%), is tested in Bottom Heated mode varying the heating power and the orientation. The static confinement diameter for Ethanol and FC-72, respectively 3.4 mm and 1.7mm, is above and slightly under the inner diameter of the tube. This is important for a better understanding of the working principle of the device very close to the limit between the Loop Thermosyphon and Pulsating Heat Pipe working modes. With respect to previous SLPHP experiments found in the literature, such device is designed with two transparent inserts mounted between the evaporator and the condenser allowing direct fluid flow visualization. Two highly accurate pressure transducers permit local pressure measurements just at the edges of one of the transparent inserts. Additionally, three heating elements are controlled independently, so as to vary the heating distribution at the evaporator. It is found that peculiar heating distributions promote the slug/plug flow motion in a preferential direction, increasing the device overall performance. Pressure measurements point out that the pressure drop between the evaporator and the condenser are related to the flow pattern. Furthermore, at high heat inputs, the flow regimes recorded for the two fluids are very similar, stressing that, when the dynamic effects start to play a major role in the system, the device classification between Loop Thermosyphon and Pulsating Heat Pipe is not that sharp anymore

Análisis etnoarqueológico del valor social del producto en sociedades cazadoras-recolectoras

This work was formulated as a consequence of considering the necessity of a value theory (that is, an economical theory), in archaeology. From our materialist perspective, that would allow us to set the basis for an objective analysis of past societies, understanding that only through the knowledge of their material life conditions and their social organization we would be able to know their historical becoming. We were reaching a common index that would make possible to compare different occupations and sites in Tierra del Fuego. This index would be used to make inferences about the amount of work invested in every occupation, amount of work that could be understood as the duration of the occupation or as the amount of people in that camp-site. On the other hand, on the basis of the Main Contradiciton formulation, we could establi sh a mechanism to quantify different participation in the production cycle and the existing differences in the access to the consumption of what has been produced. This will drive us to the formulation of a method to identify social explotation.Este trabajo surgió como consecuencia de varias preocupaciones. En primer lugar, considerábamos, desde hacía ya tiempo, la necesidad de una teoría del valor (económica, por tanto), en Arqueología; preocupación compartida con otros investigadores/as. Desde nuestra perspectiva materialista, ello nos había de permitir sentar las bases para un análisis objetivo de las sociedades prehistóricas, entendiendo que tan sólo a través delconocimiento de Las condiciones materiales de vida, y de la estructuración u organización de las relaciones sociales, podremos llegar a conocer el devenir histórico de las mismas. Buscábamos un índice, un común denominador, que nos permitiera poder comparar diferentes ocupaciones y yacimientos actualmente (y desde hace ya más de una década) en estudio en Tierra del Fuego (Argentina). Este índice debería permitirnos, por un lado realizar inferencias sobre la cantidad de trabajo invertida en cada ocupación de los diferentes asentamientos Yámana. Lo cual podría ser interpretado en clave de ti empo de ocupación o de cantidad de personas ocupando el sitio. Y por otro lado, y sobre la base de la formulación de la Contradicción Principal, podría establecer un mecanismo que nos permitiera cuantificar la participación diferencial en la producción y las disimetrías en el acceso al consumo de lo producido, estableciendo un «cálculo» para la identificación de la explotación. Este último interés tiene mucho que ver con el aceptado concepto de «sociedades igualitarias » aplicado a las sociedades cazadoras recolectoras, concepto cuestionable en tanto que surge de una aproximación androcéntrica. Este trabajo ha sido posible, en el caso de la sociedad Yámana, gracias a la exhaustiva y variada información etnográfica confrontada a una completa información arqueológica. El objetivo final es conseguir generar propuesta metodológica contrastada que nos permita este tipo de acercamientos a sociedades cazadoras-recolectoras prehistóricas

The association between human endogenous retroviruses and multiple sclerosis: a systematic review and meta-analysis

Background: The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. Objective: To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients. Methods: Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association. Results: 43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W(MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/ HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido