A note on the computation of geometrically defined relative velocities

We discuss some aspects about the computation of kinematic, spectroscopic, Fermi and astrometric relative velocities that are geometrically defined in general relativity. Mainly, we state that kinematic and spectroscopic relative velocities only depend on the 4-velocities of the observer and the test particle, unlike Fermi and astrometric relative velocities, that also depend on the acceleration of the observer and the corresponding relative position of the test particle, but only at the event of observation and not around it, as it would be deduced, in principle, from the definition of these velocities. Finally, we propose an open problem in general relativity that consists on finding intrinsic expressions for Fermi and astrometric relative velocities avoiding terms that involve the evolution of the relative position of the test particle. For this purpose, the proofs given in this paper can serve as inspiration.Comment: 8 pages, 2 figure

Intrinsic definitions of "relative velocity" in general relativity

Given two observers, we define the "relative velocity" of one observer with respect to the other in four different ways. All four definitions are given intrinsically, i.e. independently of any coordinate system. Two of them are given in the framework of spacelike simultaneity and, analogously, the other two are given in the framework of observed (lightlike) simultaneity. Properties and physical interpretations are discussed. Finally, we study relations between them in special relativity, and we give some examples in Schwarzschild and Robertson-Walker spacetimes.Comment: 29 pages, 12 figures. New proofs in special relativity and a new open problem in general relativity (see Remark 5.2). An Appendix has been added, studying the relative velocities in Schwarzschild, with new figures. Some spelling erros fixe

An update on adenosine A2A receptors as drug target in Parkinson's disease

Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A2A receptors (A2ARs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such us the dopamine D2 receptor (D2R). Furthermore, it is assumed that the formation of balanced A2AR/D2R receptor oligomers are essential for correct striatal function as the allosteric receptor-receptor interactions established within the oligomer are needed for properly sensing adenosine and dopamine. Interestingly, A2AR activation reduces the affinity of striatal D2R for dopamine and the blockade of A2AR with specific antagonists facilitates function of the D2R. Thus, it may be postulated that A2AR antagonists are pro-dopaminergic agents. Therefore, A2AR antagonists will potentially reduce the effects associated with dopamine depletion in Parkinson's disease (PD). Accordingly, this class of compounds have recently attracted considerable attention as potential therapeutic agents for PD pharmacotherapy as they have shown potential effectiveness in counteracting motor dysfunctions and also displayed neuroprotective and anti-inflammatory effects in animal models of PD. Overall, we provide here an update of the current state of the art of these A2AR-based approaches that are under clinical study as agents devoted to alleviate PD symptom

Use of venous thromboprophylaxis and adherence to guideline recommendations : a cross-sectional study

Background: Consensus Conferences and Guidelines for deep vein thrombosis prophylaxis have been published, which recommend the use of prophylactic heparins in patients with risk of venous thromboembolism (VTE). The aim of this study was the assessment of the prophylaxis of VTE and the adherence to accepted guideline recommendations throughout the hospital. Methods: A cross-sectional study was carried out in a teaching hospital after guidelines were implemented. Patients' risk factors of deep vein thrombosis, risk categories of patients, and prophylaxis used in different wards were recorded. Appropriate adherence to the guidelines was analysed. Results: Of 397 patients, prophylaxis was used in 231 patients (58%), and low-molecular-weight heparins (LMWH) were used in 224 of them (97%). Patients with prophylaxis had a higher mean number of risk factors (SD) than those without prophylaxis [3.1 (1.4) vs 1.9 (1.4); p < 0.05)]. Prophylaxis was used in 72% and 90% of moderate and high-risk patients respectively. Appropriate adherence to all guideline recommendations was observed in 42% of patients. Adherence to guidelines was high as regards the use of prophylaxis according to patients' risk factors (78%) and the use of appropriate types of prophylaxis (99%), but was low regarding appropriate heparin dosage (47%) and preoperative dosage (37%). Appropriate prophylaxis use was higher in critical care and surgical wards than in medical wards. Conclusion: Prophylaxis of VTE is generally used in risk patients, but appropriate adherence to guidelines is less frequent and variable among different wards. Continuing medical education, discussion and dissemination of guidelines, and regular clinical audit are necessary to improve prophylaxis of VTE in clinical practice

Hospital doctors' views and concerns about pharmacovigilance

Purpose: The aim of the study was to evaluate the opinions and concerns of hospital doctors about adverse drug reactions (ADRs) and pharmacovigilance. Methods: A qualitative study was undertaken using focus groups in sessions on pharmacovigilance activities conducted in thirteen clinical services of a tertiary university hospital. A total of 296 physicians participated in these sessions by giving their opinions or expressing their doubts about ADR and pharmacovigilance activities which were recorded by different observers and subsequently analysed. Results: Doctors remarked on: a) the importance, concern, frequency and specific types of ADRs that were observed in clinical practice; b) problems of clinical decision making related to the suspected ADRs; c) methods for improving detection and reporting ADRs; d) monitoring of specific ADRs or ADRs caused by specific drugs; e) and measures to prevent and minimize the risk of ADRs. Physicians expressed doubts related to: a) the basic concepts of ADRs; b) the methods of ADR identification and evaluation; c) the objectives and procedures of pharmacovigilance programmes; d) and the impact of pharmacovigilance activities. Conclusions: Hospital doctors believe that ADRs are a matter for concern in their daily clinical practice, and monitoring ADRs as well as measures for preventing the risk of ADRs are needed. Nevertheless, doctors have doubts about what an ADR is, the accuracy of diagnostic methods, the development of pharmacovigilance activities and their impact on clinical practice. Pharmacovigilance should be better explained through a continuous feedback and close relationship with hospital doctors

Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1

Cripto-1 associates with Notch1 in the endoplasmic reticulum and Golgi to enhance Notch1 localization to lipid rafts and its maturation