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Gran Dolina is a cavity infilled by at least 25 m of Pleistocene sediments divided into 12 lithostratigraphic units and 19 sedimentary facies. These sedimentary facies have been divided into allochthonous facies, defined as sediment inputs from the outside, and autochthonous facies, defined as sediments generated within the karst; but this division has been challenged in recent works. In this study, TD1 and TD2 units of Gran Dolina have been detailed studied and the use of autochthonous facies has been assessed. For that purpose, we have studied the stratigraphic excavation profile, combining field observation with laboratory sedimentary analysis (sieving, laser diffraction, and XRD) to characterize the texture and structure of the sediments. Based on these studies, a total of 8 sedimentary facies have been identified. Consequently, TD1 unit has been separated into two sub-units and 13 layers, while the TD2 unit has been divided into three sub-units. The facies associations indicate a succession of phreatic and vadose phases that would define together epiphreatic conditions inside the cave, related to the transition between Arlanzón valley terraces T3 and T4. Interior facies (and entrance facies for allochthonous facies) is proposed to define Gran Dolina's sediments since the facies analyses indicate transport by underground flows.

Existe muy poca literatura española que compare resultados oncológicos tras prostatectomía radical (PR) según la vía de abordaje y la metodología es inadecuada.

Analizar la supervivencia de los pacientes con cáncer de próstata (CP) con factores pronósticos desfavorables (FPD) tratados con PR y radioterapia de rescate (RTR) tras recidiva bioquímica (RB) y persistencia bioquímica (PB).

No están claramente definidos los patrones de recurrencia tras nefrectomía por cáncer renal.

El objetivo es comparar el rendimiento de la secuencia resonancia magnética (RM) y biopsia transrectal «cognitiva» (BTRCog) frente a la biopsia transrectal clásica (BTRCl) en pacientes con al menos una biopsia de próstata (BP) negativa.

Una de las características inherentes a los tumores renales es la capacidad de extenderse al interior del sistema venoso como trombos tumorales. El objetivo de este estudio es evaluar en los pacientes con cáncer renal en un estadio pT3apN0cM0 si la existencia de afectación tumoral venosa influye en la recidiva tumoral.

Evaluación de la efectividad de la biopsia cognitiva (BC) en los pacientes con sospecha clínica de cáncer de próstata (caP) y al menos una biopsia negativa (BTR).

La cirugía de los tumores renales con trombosis venosa está gravada con un porcentaje elevado de complicaciones y con una mortalidad perioperatoria no despreciable. Nuestro objetivo es analizar las complicaciones postoperatorias, su relación con el nivel del trombo y sus posibles factores favorecedores.

Due to their complex structure and traditional low-intensity management, Portuguese oak woodland rangelands known as montadosare often considered high nature value (HNV) farming systems, and as such, they may be deemed eligible for subsidies and incentives by governmental and nongovernmental agencies. Too little is known about how the HNV concept might be applied to conserve complex silvopastoral systems. These systems, due to their structural and functional complexity at multiple scales, tend to support high levels of biodiversity. Montados are in sharp decline as a result of the rapid specialization of land management that, through simplification, undermines multifunctionality. Understanding how changes in management influence these systems and their biodiversity is needed for prioritizing conservation efforts and for ensuring they remain HNV systems. On the basis of a field survey in 58 plots distributed among 29 paddocks on 17 farms, we conducted an integrated analysis of the relationship between grazing intensity and biodiversity in montados of similar biophysical and structural characteristics. Data on management were obtained through interviews, and biodiversity data (vegetation, macrofungi, birds, herpetofauna) were obtained through specific field protocols. Additional spatial data, such as soil characteristics, slope, land cover, and linear landscape elements, were also analyzed. The results show no overall biodiversity variation as a result of different management practices. However, different groups of species react differently to specific management practices, and within a pasture, grazing impacts are heterogenous. In low grazing intensity plots, macrofungi species richness was found to be higher, while bird species richness was lower. Using tree regeneration as proxy for montado sustainability, results show less tree regeneration in areas with higher forage quality and more intense grazing. Pathways for future progress are proposed, including creating areas within a paddock that attract grazing away from where regeneration is desired.

En esta última década se han producido avances importantes en el diagnóstico y tratamiento del cáncer de pulmón que han permitido mejorar su pronóstico. Por ello, la Sociedad Española de Radiología Médica (SERAM) y la Sociedad Española de Oncología Médica (SEOM) han elaborado un documento de consenso nacional para hacer recomendaciones sobre el diagnóstico radiológico y la valoración de la respuesta terapéutica en pacientes con cáncer de pulmón. Este grupo de expertos recomienda la tomografía computarizada multidetector (TCMD) como la técnica de elección para estudiar esta enfermedad, y respecto al informe radiológico incluir una valoración completa siguiendo el sistema de estadificación TNM. Por último, cuando el paciente reciba inmunoterapia, además de usar los criterios para evaluar la respuesta en tumores sólidos (Response Evaluation Criteria in Solid Tumors[RECIST 1.1]) también habrá que usar los criterios de respuesta inmunológica (Immune-Related Response Criteria[irRC]).

This paper presents the numerical simulation of the technology of gaseous fuel utilisation for iron ore sintering. The proposed methodology is to partially replace the solid fuel by steelworks gases. A multiphase mathematical model based on transport equations of momentum, energy and chemical species coupled with chemical reaction and phase transformations was proposed to analyse temperature distributions of the process. A base case of actual industrial operation of a large sintering machine was monitored with thermocouples inserted into the sinter bed to validate the model. The model was used to predict four cases of fuel gas utilisation: feeding from N01 to N15 wind boxes with blast furnace gas (BFG); natural gas (NG); coke oven gas (COG); and a 50–50 mixture of BFG and COG. The model predictions indicated that for all cases the sintering zone is enlarged and the solid fuel consumption could be decreased.

The feasibility of ‘solid state steelmaking’ (S3process) to meet the demand of environmental issues and higher production cost was previously studied. The S3process is the production of high carbon iron sheets from high carbon hot metal using a strip caster and a solid state decarburisation process to produce low carbon steel sheets. In the present study, the possible use of Fe–C melts with relatively low carbon contents of 1·2–1·9 mass-% as an initial hot metal source and the decarburisation behaviours of the produced hypereutectoid iron sheets from these melts were investigated to evaluate practical application. Based on the decarburisation behaviours of the hypereutectoid iron sheets and its mechanical properties, the process using Fe–C melts with 1·2 mass-%C is promising as an environmentally conscious low cost steelmaking process, although further improvements will be necessary.

The mechanisms underlying the functional improvement after injection of multipotent mesenchymal stromal cells (MSCs) in infarcted hearts remain incompletely understood. The aim of this study was to investigate if soluble factors secreted by MSCs promote cardioprotection. For this purpose, conditioned medium (CM) was obtained after three passages from MSC cultures submitted to 72 h of conditioning in serum-free DMEM under normoxia (NCM) or hypoxia (HCM) conditions. CM was concentrated 25-fold before use (NCM-25X, concentrated normoxia conditioned medium; HCM-25X, concentrated hypoxia conditioned medium). The in vitro cardioprotection was evaluated in neonatal ventricular cardiomyocytes by quantifying apoptosis after 24 h of serum deprivation associated with hypoxia (1% O2) in the absence or presence of NCM and HCM (nonconcentrated and 25-fold concentrated). The in vivo cardioprotection of HCM was tested in a model of myocardial infarction (MI) induced in Wistar male rats by permanent left coronary occlusion. Intramyocardial injection of HCM-25X (n= 14) or nonconditioned DMEM (n= 16) was performed 3 h after coronary occlusion and cardiac function was evaluated 19—21 days after medium injection. Cardiac function was evaluated by electro- and echocardiogram, left ventricular catheterization, and treadmill test. The in vitro results showed that HCM was able to decrease cardiomyocyte necrosis. The in vivo results showed that HCM-25X administered 3 h after AMI was able to promote a significant reduction (35%) in left ventricular end-diastolic pressure and improvement of cardiac contractility (15%) and relaxation (12%). These results suggest that soluble factors released in vitro by MSCs are able to promote cardioprotection in vitro and improve cardiac function in vivo.

Endometrial response to natural estradiol and low-dose vaginal progesterone replacement therapy was evaluated in 20 postmenopausal women with chronic, mild-to-moderate hypertension. A cyclic hormone replacement therapy (HRT) regimen was used (21/28 days) with percutaneous estradiol (1.5 mg/day) and vaginal micronized progesterone (100 mg/day). Menopausal symptoms decreased and estradiol concentrations increased substantially and remained in the physiological range throughout treatment. Serum gonadotropin concentrations decreased significantly (p < 0.001, Friedman's ANOVA). Bone mineral density increased by 2.1% (p = 0.029) only at the lumbar spine. Endometrial thickness remained unchanged. Breakthrough bleeding or spotting occurred in 18% of cycles in the first 3 months of HRT, 30% in months 4-9 and 22% in months 10-12. Withdrawal bleeding occurred in 40% of cycles in the first 3 months and decreased to 25% in months 10-12. At month 12, there were 11 women with amenorrhea due to endometrial atrophy. Nine women had active endometria (proliferative or secretory) and thus reported vaginal bleeding. No severe bleeding, hyperplasia, or carcinoma was found. Vaginal bleeding was tolerated, and no subject withdrew from the study. Results suggest that this regimen confers endometrial protection and is well tolerated, and can therefore safely be used for at least 1 year by postmenopausal women with hypertension and menopausal symptoms.

Damião de Góis é um dos maiores humanistas portugueses do séc. XVI. Seguramente o mais cosmopolita. Como tal, usou constantemente a língua latina na sua numerosa correspondência e em livros que escreveu. Mas nel mezzo del cammin di nostra vita empreendeu a versão do famoso tratado de Cícero sobre a Velhice, que dedicou ao Conde de Vimioso, como consolo na sua idade provecta. Só desejo que ao Professor Jabouille, que o leu no original - fazia parte das leituras para o Mestrado - tenha causado a impressão que a mim e ao próprio Damião de Góis causou, ele que com a tradução conseguiu um estilo próprio.

Seeds from the aluminum sensitive cultivar ‘Anahuac’ were treated by gamma-ray radiation. Twenty eight selected Al+3tolerant mutants were compared to the original Anahuac and the tolerant wheat cultivars IAC-24 and IAC-60 from 1994 to 1996 in acid (Capão Bonito) and limed (Monte Alegre do Sul and Tatui) soil field trials. Grain yield and agronomic characteristics were analyzed. Twenty six mutant lines yielded higher than the sensitive Anahuac cultivar in the acid soils of Capão Bonito. Under limed soil conditions, the mutants had a similar yield to the original sensitive cultivar. The majority of the mutants were similar in yield to the tolerant cultivars IAC-24 and IAC-60 under both conditions. Some of the mutants showed altered agronomic characteristics but even in these cases this will not limit its utilization. The results indicated that tolerant lines with good characteristics may be obtained from a susceptible cultivar by mutation induction, thus allowing cropping in conditions where Al+3is a limiting factor.

An HLA-B27-restricted self-octapeptide known to react with an alloreactive T-cell receptor has been modified by systematic substitution of a beta-amino acid for the natural alpha-amino acid residue, over the whole length of the parent epitope. All modified peptides were shown to bind to recombinant HLA-B*2705 and induce stable major histocompatibility complex-peptide complexes, but with some variation depending on the position of the beta-amino acid on the peptide sequence. Alteration of the natural peptide sequence at the two N-terminal positions (positions 1 and 2) decreases binding affinity and thermodynamic stability of the refolded complex, but all other positions (from position 3 to the C-terminal residue) were insensitive to the beta-amino acid substitution. All modified peptides were recognized by an alloreactive T-cell clone specific for the parent epitope with decreased efficiency, to an extent dependent of the position that was modified. Furthermore, the introduction of a single beta-amino acid at the first two positions of the modified peptide was shown to be sufficient to protect them against enzymatic cleavage. Thus, beta-amino acids represent new interesting templates for alteration of T-cell epitopes to design either synthetic vaccines of T-cell receptor antagonists.

The Beckwith-Wiedemann syndrome is a rare condition characterized by macrosomia, macroglossia, omphalocele, and visceromegaly. Although the development of neoplasia is frequent, the English literature has never described an association with mesenchymal hamartoma of the liver. We report an exceptional case of Beckwith-Wiedemann syndrome associated with a cystic mesenchymal hamartoma of the liver in a newborn.

More than one dose of measles vaccine is necessary for the sustained control of measles. The aerosol route is thought to be more immunogenic for booster doses than traditional subcutaneous injections, so we did a randomised comparative trial of aerosol and subcutaneous measles vaccines in South African schoolchildren.

Castilla y León is a rural region with a very sparse population of about 2,560,00 inhabitants. Special healthcare challenges arise due to this regions’ very aged population and large dimensions. A theoretical model of services of Telemedicine is proposed to make easier the planning of future projects. It is aimed to show the requirements and benefits of such services. Moreover, a teleradiology trial was carried out in order to obtain realistic information about the impact of Telemedicine applications on healthcare professionals and users.

Abstract:: A cross-national study of hip fracture incidence was carried out in five geographic areas – Beijing, China; Budapest, Hungary; Hong Kong; Porto Alegre, Brazil; and Reykjavik, Iceland – during the years 1990–1992. Cases of hip fracture among women and men of age 20 years and older were identified using hospital discharge data in conjunction with medical records, operating room logs, and radiology logs. Estimated incidence rates varied widely, with Beijing reporting the lowest rates (age-adjusted rate per 100 000 population for men 20 years and older = 45.4; women = 39.6) and Reykjavik the highest rates (men = 141.3; women = 274.1). Rates were higher for women than for men in every area except Beijing. In every area except Budapest, review of the operating room or radiology logs identified additional cases that were not reported in the discharge list, increasing the estimated number of hip fractures by 11% to 62%, depending on the area. Review of medical records identified miscoding of hip fractures (ICD9 820) as ‘shaft of femur and other femur fractures’ (ICD9 821) in the discharge lists of every area except Budapest, increasing the estimated number of hip fractures by 1% to 30%. The final estimates of hip fracture incidence taking into account all investigated sources of undercount and overcount ranged from 15% lower to 89% higher than an estimate based on the discharge diagnoses alone. Although these results indicate substantial limitations in relying on hospital discharge data alone to estimate hip fracture incidence rates, the extent of errors found in the discharge lists is smaller than the large international variation found here and previously reported in incidence rates. The findings support the conclusion that the differences reported among countries mainly reflect genuine variation in the hip fracture incidence rates.

HLA-B27- responder cells were stimulated in vitro with HLA-B27.1+ lymphoblastoid cell lines, and alloreactive CTL clones were obtained by limiting dilution. Three of these clones specifically lysed B27.1+ targets. In addition, they also lysed homozygous DR2 targets with various degrees of efficiency, depending on the Dw specificity of the target cell. All three clones possessed a homogeneous CD3+,CD8+,CD4- phenotype and were also homogeneous upon subcloning. Cold-target inhibition analyses showed mutual inhibition of B27.1 target lysis by DR2 targets and vice versa. Lysis of B27.1 targets was selectively inhibited by anti-class I mAbs. In contrast, lysis of DR2 targets was inhibited only by anti-class II and anti-DR monomorphic antibodies, but not by anti-class I, anti-DQw1, or anti-DP antibodies. The results indicate that these clones display dual recognition for HLA-B27.1 and for HLA-DR2 and suggest that HLA-B27.1 may share at least one epitope that is closely related to some stimulatory Dw determinants present on the HLA-DR2 antigens. Lysis of both B27+ and DR+ targets was inhibited by an anti-CD3 mAb. In contrast, an anti-CD8 antibody selectively inhibited the B27- but not the DR2-directed killing by these clones. The data support a stabilizing role of CD8 through its binding to the same class I (but not class II) molecule on the target cell bound by the T cell antigen receptor.

HLA-B27 is strongly associated with susceptibility to ankylosing spondylitis and other spondyloarthropathies. Structural analysis of this antigen has revealed the existence of multiple variants, or subtypes, in human populations. The structural microheterogeneity of these subtypes deeply affects allospecific T cell recognition and most of it occurs at an spatial cluster within the peptide binding groove of the molecule. Many polymorphic residues whose combination is unique to HLA-B27 but is conserved among subtypes are clustered in a spatially separated site of the groove from that where most subtype polymorphism occurs. Site-directed mutagenesis and DN A-mediated gene transfer has been used to show that the positions that are polymorphic among subtypes are highly relevant for modulating T cell recognition, so that immunologically silent changes do not occur. These studies have also revealed an extremely high clonotypic diversity in the alloreactive response against HLA-B27. The structural basis for this diversity has been examined by sequencing the clonotypic T cell receptors. The analysis shows a certain bias in Vβ gene segment usage, as well as other recurrent structural motives, among T cell receptor β chains from HLA-B27-specific cytotoxic T cell clones.

X-ray diffraction studies as well as structure-activity relationships indicate that the central part of class I major histocompatibility complex (MHC)-binding nonapeptides represents the main interaction site for a T cell receptor. In order to rationally manipulate T cell epitopes, three nonpeptidic spacers have been designed from the x-ray structure of a MHC-peptide complex and substituted for the T cell receptor-binding part of several antigenic peptides. The binding of the modified epitopes to the human leukocyte antigen-B*2705 protein was studied by an in vitro stabilization assay, and the thermal stability of all complexes was examined by circular dichroism spectroscopy. Depending on their chemical nature and length, the introduced spacers may be classified into two categories. Monofunctional spacers (11-amino undecanoate, (R)-3-hydroxybutyrate trimer) simply link two anchoring peptide positions (P3 and P9) but loosely contact the MHC binding groove and thus decrease more or less the affinity of the altered epitopes to human leukocyte antigen-B*2705. A bifunctional spacer ((R)-3-hydroxybutyrate tetramer) not only bridges the two distant anchoring amino acids but also strongly interacts with the binding cleft and leads to a 5-fold increase in binding to the MHC protein. To our knowledge, this is the first report of a nonpeptidic modification of T-cell receptor binding residues that significantly enhances the binding of altered peptide ligands to their host MHC protein. The presented modified ligands constitute interesting tools for perturbing the T cell response to the parent antigenic peptide.

A theoretical technique for modal study of systems with identical units is proposed. Under the assumption of identical interconnections, a motivated basic structure for understanding and analyzing linear time-invariant models of dynamic systems with identical units is developed. It is shown that for these systems there are only two kinds of modes whose associated eigenvectors satisfy two basic properties. An algorithm is presented for determination of eigenvectors and chains of generalized eigenvectors of the system by using reduced order matrices. It is shown how the technique may be applied on a system where a group of identical units is connected to other group of different units.

A strategy, based on using V beta family-specific oligonucleotides, was developed for specific amplification and direct sequencing of human TCR V beta genes. With this strategy, it was possible to undertake a structural analysis of TCRs from human T cell clones in specific responses. 12 HLA-B27-specific cytotoxic clones were examined. The results reveal a nonrandom use of V beta gene diversity in this alloreactive response in that: (a) the clones express a restricted number of V beta segments, including a subset of V beta families that are significantly more related to one another than to most other V beta families; (b) five of seven clones having a particular reaction pattern with HLA-B27 subtypes possess Alanine at the D-J junction; and (c) identical J beta segments are found associated in several instances with identical or highly homologous V beta gene segments. In addition, two new V beta 13 members are reported.

The complete amino acid sequence for papain-solubilized HLA-B7 heavy chain is compared with the partial sequences of HLA-A2 and H-2Kb heavy chains. Although these molecules are highly conserved (i.e., 80% homology in comparing HLA-B7 with HLA-A2; 72% and 74% homology in comparing H-2Kb with HLA-A2 and HLA-B7, respectively), two stretches of greater variability are observed. These clusters of variability are discussed in terms of their possible involvement in the alloantigenic determinant(s) characteristic of these highly polymorphic membrane antigens.

Current ideas on the structure, evolution, and disease association of HLA- B27 antigens are presented, with emphasis on the effect of HLA- B27 polymorphism on T- cell recognition and antigen- presenting properties of these molecules. The molecular relationship between HLA-B27 and HLA-B73, and its implications for a putative pathogenetic role of the later antigen are discussed.

Previous experiments have shown that intraventricular injection of ovine corticotropin (ACTH)-releasing factor (oCRF) in doses too low to elevate plasma ACTH by direct action on the pituitary does not lower plasma ACTH, suggesting that the peptide lacks a negative ultrashort-loop feedback action to suppress its own release under resting conditions. The present study was performed to determine whether oCRF has any action to alter CRF release in stress. The peptide was injected into the third ventricle or external jugular vein of freely moving ovariectomized female rats 5 min prior to application of ether stress. When oCRF was injected into the third ventricle in doses of 500 pg (0.1 pmol) or less, there was no significant alteration in plasma ACTH prior to ether stress; however, there was a significantly enhanced increase in plasma ACTH 2 and 5 min after ether stress applied 5 min after intraventricular injection of oCRF at doses of 50 (0.01 pmol) or 150 pg (0.03 pmol). These results suggest that the peptide acts on structures adjacent to the third ventricle to augment stress-induced CRF release. To rule out the possibility that the sensitivity of the pituitary itself to CRF increases dramatically following stress, 10 or 100 ng of oCRF was injected i.v. These doses produced a significant dose-related increase in plasma ACTH at 2, 5, or 15 min. In other groups receiving the same doses of oCRF and ether stressed 5 min later, plasma ACTH was significantly higher 2 or 5 min after ether stress when compared with plasma ACTH in ether-stressed saline-injected animals. However, in contrast with the results of intraventricular injection of oCRF, the release of ACTH was no greater than that obtained by summing the independent effects of exogenous oCRF and the CRF released by stress. We conclude that CRF may have a positive ultrashort-loop feedback action to enhance stress-induced ACTH release and that this enhancement is not due to increased sensitivity of anterior pituitary corticotrophs to CRF.

The effect of HLA-B27 polymorphism on antigen presentation was analysed by comparing the binding of three Epstein-Barr virus-derived peptide epitopes to HLA-B27 subtypes with their immunogenicity and antigenicity in the context of these subtypes. The effect of altering the major anchor residue Arg2 on binding or on recognition by peptide-specific cytotoxic T lymphocytes (CTL) was also examined. The three peptides bound significantly to all the B*2701-B*2706 subtypes. This did not correlate with the peptides being immunogenic or recognized by specific CTL in the context of only particular subtypes. In addition, of the three viral epitopes tested, those that were immunogenic in B*2702- or B*2705-restricted responses bound to these subtypes less efficiently than one peptide that was immunogenic only in the B*2704 context. Thus, among several potentially immunogenic peptides from the same virus, the antiviral response is not necessarily directed against the one that binds best to the restricting subtype. These results indicate that HLA-B27 polymorphism influences antigen presentation in ways other than simply peptide affinity. Synthetic analogues lacking the canonical Arg2 motif of HLA-B27-bound peptides, even when binding much worse to the restricting subtype, were recognized equally by CTL specific for the parental peptide. This indicates that Arg2 is not required to maintain the structure of the epitope. The implications of these results for pathogenetic models of HLA-B27-associated disease are discussed.