Minimal clinically meaningful differences for the eortc QLQ-C30 and eortc QLQ-Bn20 scales in brain cancer patients

Objective: The aim of this study was to determine the smallest changes in health-related quality of life (HRQOL) scores in the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the EORTC Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. Methods: World Health Organization (WHO) performance status (PS) and the Mini Mental State Examination (MMSE) were used as clinical anchors to determine minimal clinically important differences (MCID) in HRQOL change scores (range 0 - 100) in the EORTC QLQ-C30 and QLQ-BN20. Anchor-based MCID estimates less than 0.2SD (small effect) were not recommended for interpretation. Other selected distribution-based methods were also used for comparison purposes. Results: Based on WHO PS, our findings support the following whole number estimates of the MCID for improvement and deterioration respectively: physical functioning (6, 9), role functioning (14, 12), cognitive functioning (8, 8), global health status (7, 4*), fatigue (12, 9) and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and those for communication deficit were (9, 7). The estimates with asterisks were less that the set 0.2 SD threshold and are therefore not recommended for interpretation. Our MCID estimates therefore range from 5-14. Conclusion: These estimates can help clinicians to evaluate changes in HRQOL over time and, in conjunction with other measures of efficacy, help to assess the value of a health care intervention or to compare treatments. Furthermore, the estimates can be useful in determining sample sizes in the design of future clinical trials.

Implementació de les físiques d'un vehicle en un videojoc 3D

En la carrera del mundo de los videojuegos por alcanzar insospechables cotas de realismo con las que seguir sorprendiendo y enganchando al público, los motores de física se han convertido en la herramienta de presente y futuro. Atraídos por el auge de esta nueva tecnología, hemos lidiado con los motores referencia hoy día en el mercado, seleccionando luego uno de ellos e implementando un humilde videojuego de carreras como muestra de su potencial y de los conocimientos adquiridos.

Detachment of cell surface-bound anticarcinoembryonic antigen immune complexes by phospholipase C.

CEA as well as normal cross-reacting antigens (NCA) are fixed to the cell membrane via phosphatidylinositol (PI). To find out whether these antigens are internalized after antibody contact, acid pH desorption was compared to phospholipase C (PLC)-mediated cleavage of the antigen anchor. With the former procedure, marked differences in the desorbability of individual MAbs were noted, while PLC was able to cleave off surface-bound immune complexes irrespective of the MAb involved. From this it is concluded that internalization of MAb complexes of CEA/NCA, if occurring at all, is a low efficiency process.

Sperm Ultrastructure of the Spider Crab Maja brachydactyla (Decapoda: Brachyura)

This study describes the morphology of the sperm cell of Maja brachydactyla, with emphasis on localizing actin and tubulin. The spermatozoon of M. brachydactyla is similar in appearance and organization to other brachyuran spermatozoa. The spermatozoon is a globular cell composed of a central acrosome, which is surrounded by a thin layer of cytoplasm and a cup-shaped nucleus with four radiating lateral arms. The acrosome is a subspheroidal vesicle composed of three concentric zones surrounded by a capsule. The acrosome is apically covered by an operculum. The perforatorium penetrates the center of the acrosome and has granular material partially composed of actin. The cytoplasm contains one centriole in the subacrosomal region. A cytoplasmic ring encircles the acrosome in the subapical region of the cell and contains the structures-organelles complex (SO-complex), which is composed of a membrane system, mitochondria with few cristae, and microtubules. In the nucleus, slightly condensed chromatin extends along the lateral arms, in which no microtubules have been observed. Chromatin fibers aggregate in certain areas and are often associated with the SO-complex. During the acrosomal reaction, the acrosome could provide support for the penetration of the sperm nucleus, the SO-complex could serve as an anchor point for chromatin, and the lateral arms could play an important role triggering the acrosomal reaction, while slightly decondensed chromatin may be necessary for the deformation of the nucleus.

Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.

In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1). In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.

Characterization of two receptors for TRAIL.

Two receptors for TRAIL, designated TRAIL-R2 and TRAIL-R3, have been identified. Both are members of the tumor necrosis factor receptor family. TRAIL-R2 is structurally similar to the death-domain-containing receptor TRAIL-R1 (DR-4), and is capable of inducing apoptosis. In contrast, TRAIL-R3 does not promote cell death. TRAIL-R3 is highly glycosylated and is membrane bound via a putative phosphatidylinositol anchor. The extended structure of TRAIL-R3 is due to the presence of multiple threonine-, alanine-, proline- and glutamine-rich repeats (TAPE repeats). TRAIL-R2 shows a broad tissue distribution, whereas the expression of TRAIL-R3 is restricted to peripheral blood lymphocytes (PBLs) and skeletal muscle. All three TRAIL receptors bind TRAIL with similar affinity, suggesting a complex regulation of TRAIL-mediated signals.

Criminología positivista y anarqusimo en la España de entresiglos (XIX-XX): un debate sobre la naturaleza, la ciencia y el progreso

El estudio hasta el momento de la relación entre positivismo criminológico e ideario anarquista de entre siglos (XIX-XX), ha evidenciado la trascendencia del estudio de aquellos dos pensamiento en esa etapa histórica. El desarrollo de la Criminología como ciencia, así como del verdadero núcleo teórico y práctico del anarquismo español, se encuentra en aquel momento histórico de cambio de siglo. La construcción del tipo criminal anarquista, la política criminal desarrollada al efecto, así como las críticas, propuesta y posturas acerca de la cuestión criminal por parte de los anarquistas, revelan un auge discursivo y científico de ambas partes que estaban discutiendo sobre temas verdaderamente de fondo: aquellos sobre la naturaleza, el progreso y la forma de sociedad y Estado. Más allá de las disputas con aquellos autores de la Scuola Italiana, los anarquistas españoles, avivaron un interés decisivo en otro tipo de teorías como el darwinismo o el neomalthusianismo. Más allá del vehemente rechazo a la cárcel y al sistema estatal y capitalista en su conjunto, el desarrollo y utilización en propio sentido de la Ciencia, se fundamentó como herramienta política básica para el pensamiento anarquista. Por su parte, esa misma Ciencia positiva, era el comodín “objetivo” que se usaba de herramienta para una criminalización y persecución política de numerosas disidencias. Desentrañar, por un lado, cómo se articuló cada uno de esos discursos y qué implicaciones y relaciones tuvo, y por otro, qué herencia pervive de aquellas construcciones en nuestro sistema penal y político, son los puntos centrales de esta Tesis.

Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.

In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1). In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.

A Multiplex-PCR approach to identification of the Brazilian intermediate hosts of Schistosoma mansoni

Due to difficulties concerning morphological identification of planorbid snails of the genus Biomphalaria, and given a high variation of characters and in the organs with muscular tissue, we designed specific polymerase chain reaction (PCR) primers for Brazilian snail hosts of Schistosoma mansoni from available sequences of internal transcribed spacer 2 (ITS2) of the ribosomal RNA gene. From the previous sequencing of the ITS2 region, one primer was designed to anchor in the 5.8S conserved region and three other species-specific primers in the 28S region, flanking the ITS2 region. These four primers were simultaneously used in the same reaction (Multiplex-PCR), under high stringency conditions. Amplification of the ITS2 region of Biomphalaria snails produced distinct profiles (between 280 and 350 bp) for B. glabrata, B. tenagophila and B. straminea. The present study demonstrates that Multiplex-PCR of ITS2-DNAr showed to be a promising auxiliary tool for the morphological identification of Biomphalaria snails, the intermediate hosts of S. mansoni.

Evaluation of somatic cell variants deficient in glycosylphosphatidyl-inositol anchoring as candidates for genetic correction.

Many cell surface glycoproteins are anchored in the lipid bilayer by a glycosylphosphatidyl-inositol (GPI) structure. Recently, a number of cell lines which are deficient in the biosynthesis and/or addition of this anchor have been described. In this report, we summarize the current knowledge on these lines and discuss their potential use to isolate the genes involved in the GPI anchor biosynthetic pathway with a specific emphasis on L cell fibroblasts.

A mucin like gene different from the previously reported members of the mucin like gene families is transcribed in Trypanosoma cruzi but not in Trypanosoma rangeli

Trypanosoma cruzi expresses mucin like glycoproteins encoded by a complex multigene family. In this work, we report the transcription in T. cruzi but not in T. rangeli of a mucin type gene automatically annotated by the T. cruzi genome project. The gene showed no nucleotide similarities with the previously reported T. cruzi mucin like genes, although the computational analysis of the deduced protein showed that it has the characteristic features of mucins: a signal peptide sequence, O-glycosylation sites, and glycosylphosphatidylinositol (GPI) anchor sequence. The presence in this gene of N- terminal and C- terminal coding sequences common to other annotated mucin like genes suggests the existence of a new mucin like gene family.

Cifrado de ficheros mediante DES-CBC

En aquest projecte i davant de l'actual explosió en els serveis de transmissió electrònica d'informació, es pretén fer una anàlisi del sistema de xifrat DES (Data Encryption Standard), des del punt de vista instructiu perquè pugui ser utilitzat en el futur com a element d'ensenyament per facilitar la compressió del seu funcionament.

Diseño e implementación de un capturador de paquetes de red

En l'actualitat les xarxes de comunicacions són bàsicament digitals; el camí que s'ha avançat en els darrers quaranta anys ha estat molt llarg, amb un desenvolupament tan ràpid que ha fet que qualsevol previsió quedés molt endarrerida abans d'hora (o que de vegades se sobreestimés aquest desenvolupament, com va passar amb el

Fully engaged: tackling health inequalities through public health interventions

The evolving role of Primary Care Trusts (PCTs) is currently centre stage, with fundamental debate emerging from Commissioning a patient-led NHS and Our health, our care, our say a new direction for community services. This paper argues that PCTs have a crucial role to play in the public health agenda, specifically tackling health inequalities. This responsibility will become even stronger as the present wave of reforms gains momentum. There is also a lively debate on whether these reforms will make inroads into the persistent problem of health inequality or will exacerbate them even further unless robust, additional intervention levers and mechanisms are introduced. This paper suggests that PCTs will be central to ensuring the balance of reforms is tilted towards a more rather than a less equitable NHS. One of the key responsibilities for PCTs outlined by the Department of Health1 will be to act as the anchor at local level to the increasingly diverse and potentially3fragmented NHS. By using their crucial commissioning role to provide overall coherence to the health system, acting as leading local champions of the NHS and continuing the drive for improvement in access and quality, PCTs will have to act as enforcer and guardian of the equity of the NHS at local level. There is widespread evidence of the tenacity of health inequalities in Great Britain. This report looks at the measures that a fully engaged۝3 PCT has taken to grapple with the issues and draws some conclusions as to their possible wider application.refer to the resource

Immunization with synthetic peptides containing a defined malaria epitope induces a highly diverse cytotoxic T lymphocyte response. Evidence that two peptide residues are buried in the MHC molecule.

In the present study, we have explored ways of inducing a CTL response to a previously defined H-2Kd MHC class I restricted epitope in the circumsporozoite (CS) protein of Plasmodium berghei, and studied in detail the fine specificity of the response. We found that the s.c. injection of a variety of synthetic peptides emulsified in Freund's adjuvant efficiently induced a specific CTL response in (BALB/c x C57BL/6)F1 (H-2d x H-2b) mice. In contrast, BALB/c mice responded only marginally, consistent with the possible requirement for a concomitant Th response that would be provided by the C57BL/6 strain. Similar to our previous observations in analyzing CTL clones from sporozoite-immunized mice, the CTL response induced by peptide immunization was in part cross-reactive with an epitope from the Plasmodium yoelii species. The minimal P. berghei CS epitope, the octapeptide PbCS 253-260, was studied in detail by the analysis of a series of variant CS peptides containing single Ala substitutions. The relative antigenic activity for each variant peptide was calculated for 28 different CTL clones. Overall, the response to this P. berghei CTL epitope appeared to be extremely diverse in terms of fine specificity. This was evident among the CTL derived from sporozoite-immunized mice, as well as among those from peptide-immunized animals. The heterogeneity found at the functional level correlates with the highly diverse TCR repertoire that we have found for the same series of CTL clones in a study that is reported separately. The relative competitor activity for each Ala-substituted peptide was also determined in a quantitative functional competition assay. For the residues (Tyr253 and Ile260) within the 8-mer CS peptide, substitution with Ala reduced competitor activity by at least 40-fold, and for two others the reduction was 5- to 10-fold. When the relative antigenic activity for each CTL/peptide combination was normalized to the relative competitor activity of the peptide, a striking pattern emerged. The two residues that most affected competitor activity showed no additional effect on recognition beyond that observed for competition. In marked contrast, Ala substitutions at the other five positions tested varied widely, depending on the CTL/peptide combination. This pattern not only supports a model whereby the Tyr253 and Ile260 residues anchor the peptide to the Kd molecule, but also implies that they are virtually inaccessible to the TCR.