Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints.

Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: Relationship to gender, subjective health, smoking habits, and 10-year mortality

The decrease with age of the adrenal-secreted dehydroepiandrosterone sulfate (DHEAS) in serum has suggested that it may be causally related to longevity. For the PAQUID [People (Personnes) Aged (Agées) About What (Quid, in Latin)] cohort of elderly subjects, we have previously reported higher DHEAS in men than in women, a decrease with age and, among men, a negative correlation between the DHEAS level and mortality at 2 and 4 years. Here, with an 8-year followup in 290 subjects, we show a global decrease of 2.3% per year for men and 3.9% per year for women. However, in approximately 30% of cases, there was an increase of DHEAS. We observed no relationship between the evolution of DHEAS level and functional, psychological, and mental status, possibly because of selection by death. In women, no association was found between mortality and DHEAS level. In men, the relative risk (RR) of death was higher for the lowest levels of DHEAS (RR = 1.9, P = 0.007), with RR = 6.5, P = 0.003 for those under 70 years old, a result indicating heterogeneity of the population. There was an effect of subjective health on mortality that disappeared after adjustment of DHEAS levels, suggesting its relation with these DHEAS levels. Death RR was much higher in smokers with a low DHEAS level than in nonsmokers with high DHEAS (RR = 6.7, P = 0.001). We submit that the involvement of DHEAS is possibly different according to gender, that association between low DHEAS level and mortality only for men under 70 years old possibly reflects heterogeneity of the population, and that DHEAS level is a reliable predictor of death in male smokers.

Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.

The dopamine hypothesis of schizophrenia proposes that hyperactivity of dopaminergic transmission is associated with this illness, but direct observation of abnormalities of dopamine function in schizophrenia has remained elusive. We used a newly developed single photon emission computerized tomography method to measure amphetamine-induced dopamine release in the striatum of fifteen patients with schizophrenia and fifteen healthy controls. Amphetamine-induced dopamine release was estimated by the amphetamine-induced reduction in dopamine D2 receptor availability, measured as the binding potential of the specific D2 receptor radiotracer [123I] (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl]benzamide ([123I]IBZM). The amphetamine-induced decrease in [123I]IBZM binding potential was significantly greater in the schizophrenic group (-19.5 +/- 4.1%) compared with the control group (-7.6 +/- 2.1%). In the schizophrenic group, elevated amphetamine effect on [123I]IBZM binding potential was associated with emergence or worsening of positive psychotic symptoms. This result suggests that psychotic symptoms elicited in this experimental setting in schizophrenic patients are associated with exaggerated stimulation of dopaminergic transmission. Such an observation would be compatible with an abnormal responsiveness of dopaminergic neurons in schizophrenia.

Loss of high-affinity prostacyclin receptors in platelets and the lack of prostaglandin-induced inhibition of platelet-stimulated thrombin generation in subjects with spinal cord injury.

Coronary artery disease is a leading cause of death in individuals with chronic spinal cord injury (SCI). However, platelets of those with SCI (n = 30) showed neither increased aggregation nor resistance to the antiaggregatory effects of prostacyclin when compared with normal controls (n = 30). Prostanoid-induced cAMP synthesis was similar in both groups. In contrast, prostacyclin, which completely inhibited the platelet-stimulated thrombin generation in normal controls, failed to do so in those with SCI. Scatchard analysis of the binding of [3H]prostaglandin E1, used as a prostacyclin receptor probe, showed the presence of one high-affinity (Kd1 = 8.11 +/- 2.80 nM; n1 = 172 +/- 32 sites per cell) and one low-affinity (Kd2 = 1.01 +/- 0.3 microM; n2 = 1772 +/- 226 sites per cell) prostacyclin receptor in normal platelets. In contrast, the same analysis in subjects with SCI showed significant loss (P < 0.001) of high-affinity receptor sites (Kd1 = 6.34 +/- 1.91 nM; n1 = 43 +/- 10 sites per cell) with no significant change in the low affinity-receptors (Kd2 = 1.22 +/- 0.23; n2 = 1820 +/- 421). Treatment of these platelets with insulin, which has been demonstrated to restore both of the high- and low-affinity prostaglandin receptor numbers to within normal ranges in coronary artery disease, increased high-affinity receptor numbers and restored the prostacyclin effect on thrombin generation. These results demonstrate that the loss of the inhibitory effect of prostacyclin on the stimulation of thrombin generation was due to the loss of platelet high-affinity prostanoid receptors, which may contribute to atherogenesis in individuals with chronic SCI.

Phosphorylated α-synuclein-immunoreactive retinal neuronal elements in Parkinson's disease subjects

Visual symptoms are relatively common in Parkinson's disease (PD) and optical coherence tomography has indicated possible retinal thinning. Accumulation of aggregated α-synuclein is thought to be a central pathogenic event in the PD brain but there have not as yet been reports of retinal synucleinopathy. Retinal wholemounts were prepared from subjects with a primary clinicopathological diagnosis of PD (N = 9), dementia with Lewy bodies (DLB; N = 3), Alzheimer's disease (N = 3), progressive supranuclear palsy (N = 2) as well as elderly normal control subjects (N = 4). These were immunohistochemically stained with an antibody against α-synuclein phosphorylated at serine 129, which is a specific molecular marker of synucleinopathy. Phosphorylated α-synuclein-immunoreactive (p-syn IR) nerve fibers were present in 7/9 PD subjects and in 1/3 DLB subjects; these were sparsely distributed and superficially located near or at the inner retinal surface. The fibers were either long and straight or branching, often with multiple en-passant varicosities along their length. The straight fibers most often had an orientation that was radial with respect to the optic disk. Together, these features are suggestive of either retinopetal/centrifugal fibers or of ganglion cell axons. In one PD subject there were sparse p-syn IR neuronal cell bodies with dendritic morphology suggestive of G19 retinal ganglion cells or intrinsically photosensitive ganglion cells. There were no stained nerve fibers or other specific staining in any of the non-PD or non-DLB subjects. It is possible that at least some of the observed visual function impairments in PD subjects might be due to α-synucleinopathy.

Experiences Using an Open Source Sofware Library to Teach Computer Vision Subjects

Machine vision is an important subject in computer science and engineering degrees. For laboratory experimentation, it is desirable to have a complete and easy-to-use tool. In this work we present a Java library, oriented to teaching computer vision. We have designed and built the library from the scratch with enfasis on readability and understanding rather than on efficiency. However, the library can also be used for research purposes. JavaVis is an open source Java library, oriented to the teaching of Computer Vision. It consists of a framework with several features that meet its demands. It has been designed to be easy to use: the user does not have to deal with internal structures or graphical interface, and should the student need to add a new algorithm it can be done simply enough. Once we sketch the library, we focus on the experience the student gets using this library in several computer vision courses. Our main goal is to find out whether the students understand what they are doing, that is, find out how much the library helps the student in grasping the basic concepts of computer vision. In the last four years we have conducted surveys to assess how much the students have improved their skills by using this library.

Methodology based on registration techniques for representing subjects and their deformations acquired from general purpose 3D sensors

In this thesis a methodology for representing 3D subjects and their deformations in adverse situations is studied. The study is focused in providing methods based on registration techniques to improve the data in situations where the sensor is working in the limit of its sensitivity. In order to do this, it is proposed two methods to overcome the problems which can difficult the process in these conditions. First a rigid registration based on model registration is presented, where the model of 3D planar markers is used. This model is estimated using a proposed method which improves its quality by taking into account prior knowledge of the marker. To study the deformations, it is proposed a framework to combine multiple spaces in a non-rigid registration technique. This proposal improves the quality of the alignment with a more robust matching process that makes use of all available input data. Moreover, this framework allows the registration of multiple spaces simultaneously providing a more general technique. Concretely, it is instantiated using colour and location in the matching process for 3D location registration.

Development of multidisciplinary workshops between different subjects as an innovative teaching methodology for the acquisition of professional skills of the future architect

The implantation of the new Architecture Degree and the important normative changes in the building sector imply the need to use new teaching methodologies that enhance skills and competences in order to response to the increasing requirements demanded by society to the future architect. The aim of this paper is to present, analyze and discuss the development of multidisciplinary workshops as a new teaching methodology used in several Construction subjects of the Architecture Degree in the University of Alicante. Workshops conceived with the aim to synthesize and complement the technical knowledge acquired by the students during the Degree and to enhance the skills and competencies necessary for the professional practice. With that purpose, we decided to experiment on current subjects of the degree during this academic year, by applying the requirements defined in the future Architecture Degree in a practical way, through workshops between different subjects, superposing the technical knowledge with the resolution of constructive problems in the development of an architectural project. Developing these workshops between subjects we can dissolve the traditional boundaries between different areas of the Degree. This multidisciplinary workshop methodology allows the use of all the global knowledge acquired by students during their studies and at the same time, it enhances students’ ability to communicate and discuss their ideas and solutions in public. It also increases their capacity of self-criticism, and it foments their ability to undertake learning strategies and research in an autonomous way. The used methodology is based on the development of a practical work common to several subjects of different knowledge areas within the "Technology Block" of the future Architecture Degree. Thus, students work approaching the problem in a global way discussing simultaneously with teachers from different areas. By using these new workshops we stimulate an interactive class versus a traditional lecture. Work is evaluated continuously, valuing the participative pupil´s attitude, working in groups in class time, reaching weekly objectives and stimulating the individual responsibility and positive interdependence of the pupil inside the working group. The exercises are designed to improve students’ ability to transmit their ideas and solutions in public, knowing how to discuss and defend their technical resolutions to peers and teachers (Peer Reviewing), their capacity for self-criticism and their capacity to undertake strategies and autonomous learning processes at the same time they develop a personal research into new technologies, systems and materials. Students have shown their majority preference for this teaching methodology by the multidisciplinary workshops offered in the last years, with very satisfactory academic results. In conclusion, it can be verified nowadays the viability of the introduction of new contents and new teaching methodologies necessary for the acquisition of the skills in the future Architecture Degree, through workshops between several subjects that have had a great acceptance in students and positive contrasted academic results.

A guide to reading in social ethics and allied subjects: lists of books and articles selected and described for the use of general readers

by teachers in Harvard University.

Subjects suggested by Edward Everett, 1823, undated

Four letters in the hand of Edward Everett, the Eliot Professor of Greek Literature from 1815 until 1826, containing suggested subjects and questions for President Kirkland. Three of the documents are undated and one is dated November 5, 1823.

Subjects suggested by John Webster, 1826 July

A handwritten letter with suggested subjects from John White Webster, a lecturer of chemistry, mineralogy, and geology at the Harvard Medical College from 1824 until 1827, when he was appointed the Erving Professor of Chemistry (1827-1850).

Subjects suggested by John Farrar, ca. 1820s

A handwritten letter to President John Thornton Kirkland with five suggested subjects from John Farrar, the Hollis Professor of Mathematics and Natural Philosophy from 1807 until 1836.

Subjects suggested by Levi Hedge, ca. 1820s

A handwritten letter to President Kirkland with three suggested questions from Levi Hedge, a professor of logic and metaphysics from 1810 to 1827, and the Alford Professor of Natural Religion, Moral Philosophy, and Civil Polity from 1827 to 1832.

Subjects suggested by Andrews Norton, ca. 1820s

Four documents with suggested questions in the hand of Andrews Norton, Dexter Lecturer on Biblical Literature from 1813 to 1830. One of the documents is signed by Norton and addressed to President Kirkland.