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Background The modified thrombolysis in cerebral infarction (mTICI) scale is a widely used and validated qualitative tool to evaluate angiographic intracerebral inflow following endovascular thrombectomy (EVT). We validated a machine-learning (ML) algorithm to grade digital subtraction angiograms (DSA) using the mTICI scale. Materials and methods We included angiograms of identified middle cerebral artery (MCA) occlusions who underwent EVT. The complete DSA sequences were preprocessed and normalized. We created three convolutional neural networks to classify DSA into two outcomes, low- (mTICI 0,1,2a) and high-grade (mTICI 2b,2c,3). Results We included a total of 234 angiograms in this study. The area under the receiver operating characteristic was 0.863 (95% CI 0.816-0.909), 0.914 (95% CI 0.876-0.951), and 0.890 (95% CI 0.848-0.932) for the anteroposterior (AP), lateral (L), and combined models, respectively, when dichotomizing outcomes into low and high grade. The models' area under the precision-recall curve was 0.879 (95% CI 0.829-0.930), 0.906 (95% CI 0.844-0.968), and 0.887 (95% CI 0.834-0.941) for the AP, L, and combined models. Conclusion In complete cerebral DSA, our angiography-based ML strategy was able to predict mTICI scores following EVT rapidly and reliably for MCA occlusions.

Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) are essential tools in radiation oncology. In Spain, the use of these techniques continues to grow as older linear accelerators (linacs) are replaced with modern equipment. However, little is known about inter-centre variability in prescription and dose heterogeneity limits. Consequently, the SBRT-Spanish Task Group (SBRT-SG) of the Spanish Society of Radiation Oncology (SEOR) has undertaken an initiative to assess prescription and homogeneity in SRS/SBRT treatment. In the present study, we surveyed radiation oncology (RO) departments to obtain a realistic overview of prescription methods used for SBRT and SRS treatment in Spain. A brief survey was developed and sent to 34 RO departments in Spain, mostly those who are members of the SEOR SBRT-SG. The survey contained seven questions about the specific prescription mode, dose distribution heterogeneity limits, prescription strategies according to SRS/SBRT type, and the use of IMRT–VMAT (Intensity Modulated Radiation Therapy–Volumetric Modulated Arc Therapy). Responses were received from 29 centres. Most centres (59%) used the prescription criteria D95% ≥ 100%. Accepted dose heterogeneity was wide, ranging from 107 to 200%. Most centres used IMRT–VMAT (93%). This survey about SRS/SBRT prescription and dose heterogeneity has evidenced substantial inter-centre variability in prescription criteria, particularly for intended and accepted dose heterogeneity. These differences could potentially influence the mean planning target volume dose and its correlation with treatment outcomes. The findings presented here will be used by the SEOR SBRT-SG to develop recommendations for SRS/SBRT dose prescription and heterogeneity.

Today, patient management generally requires a multidisciplinary approach. However, due to the growing knowledge base and increasing complexity of Medicine, clinical practice has become even more specialised. Radiation oncology is not immune to this trend towards subspecialisation, which is particularly evident in ablative radiotherapy techniques that require high dose fractions, such as stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). The aim of the present report is to establish the position of the Spanish Society of Radiation Oncology (SEOR), in collaboration with the Spanish Society of Medical Physics (SEFM), with regard to the roles and responsibilities of healthcare professionals involved in performing SRS and SBRT. The need for this white paper is motivated due to the recent changes in Spanish Legislation (Royal Decree [RD] 601/2019, October 18, 2019) governing the use and optimization of radiotherapy and radiological protection for medical exposure to ionizing radiation (article 11, points 4 and 5) [1 ], which states: “In radiotherapy treatment units, the specialist in Radiation Oncology will be responsible for determining the correct treatment indication, selecting target volumes, determining the clinical radiation parameters for each volume, directing and supervising treatment, preparing the final clinical report, reporting treatment outcomes, and monitoring the patient’s clinical course.” Consequently, the SEOR and SEFM have jointly prepared the present document to establish the roles and responsibilities for the specialists—radiation oncologists (RO), medical physicists (MP), and related staff —involved in treatments with ionizing radiation. We believe that it is important to clearly establish the responsibilities of each professional group and to clearly establish the professional competencies at each stage of the radiotherapy process.

Purpose Peer review has been proposed as a strategy to ensure patient safety and plan quality in radiation oncology. Despite its potential benefits, barriers commonly exist to its optimal implementation in daily clinical routine. Our purpose is to analyze peer-review process at our institution. Methods and materials Based on our group peer-review process, we quantified the rate of plan changes, time and resources needed for this process. Prospectively, data on cases presented at our institutional peer-review conference attended by physicians, resident physicians and physicists were collected. Items such as time to present per case, type of patient (adult or pediatric), treatment intent, dose, aimed technique, disease location and receipt of previous radiation were gathered. Cases were then analyzed to determine the rate of major change, minor change and plan rejection after presentation as well as the median time per session. Results Over a period of 4 weeks, 148 cases were reviewed. Median of attendants was six physicians, three in-training-physicians and one physicist. Median time per session was 38 (4–72) minutes. 59.5% of cases presented in 1–4 min, 32.4% in 5–9 min and 8.1% in ≥ 10 min. 79.1% of cases were accepted without changes, 11.5% with minor changes, 6% with major changes and 3.4% were rejected with indication of new presentation. Most frequent reason of change was contouring corrections (53.8%) followed by dose or fractionation (26.9%). Conclusion Everyday group consensus peer review is an efficient manner to recollect clinical and technical data of cases presented to ensure quality radiation care before initiation of treatment as well as ensuring department quality in a feedback team environment. This model is feasible within the normal operation of every radiation oncology Department.

Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) is the most common pulmonary complication of RA, increasing morbidity and mortality. Anti-citrullinated protein antibodies have been associated with the development and progression of both RA and fibrotic lung disease; however, the role of protein citrullination in RA-ILD remains unclear. Here, we demonstrate that the expression of peptidylarginine deiminase 2 (PAD2), an enzyme that catalyzes protein citrullination, is increased in lung homogenates from subjects with RA-ILD and their lung fibroblasts. Chemical inhibition or genetic knockdown of PAD2 in RA-ILD fibroblasts attenuated their activation, marked by decreased myofibroblast differentiation, gel contraction, and extracellular matrix gene expression. Treatment of RA-ILD fibroblasts with the proteoglycan syndecan-2 (SDC2) yielded similar antifibrotic effects through regulation of PAD2 expression, phosphoinositide 3-kinase/Akt signaling, and Sp1 activation in a CD148-dependent manner. Furthermore, SDC2-transgenic mice exposed to bleomycin-induced lung injury in an inflammatory arthritis model expressed lower levels of PAD2 and were protected from the development of pulmonary fibrosis. Together, our results support a SDC2-sensitive profibrotic role for PAD2 in RA-ILD fibroblasts and identify PAD2 as a promising therapeutic target of RA-ILD.

This research focusses on a complex precipitation (Ni3(Ti,Al)) hardenable metastable stainless steel. Dual phase (austenite, γ/martensite, α′) and ultrafine grained austenitic microstructures obtained after applying isochronal heat treatments (0.1–10 ℃/s) to a cold-rolled (CR) metastable stainless steel have been microstructurally and mechanically characterized using different experimental techniques (optical microscopy, SEM, TEM, magnetic measurements, tensile tests). A wide range of strength (2.1–1.1 GPa) and elongation (3–25%) values have been obtained using sub-size samples (7 mm in gauge length). The scientific aim is the understanding of those microstructural parameters and mechanisms that influence the achievement of ultra-fine grained microstructures and control or the mechanical behaviour of different complex microstructures in this type of steels. Whereas the industrial aim would be to expand the applicability of this steel and use this scientific knowledge to design steels with optimized microstructures and mechanical properties.

To investigate the effect of cervical spondylosis (CS) in the brain with a combination of advanced neuroimaging techniques.Twenty-seven patients with CS and 24 age- and gender-matched healthy controls were studied. Disease severity was quantified using the Modified Japanese Orthopaedic Association Scoring System (mJOHA). Magnetic resonance (MR) imaging of the brain and spinal cord, functional MR imaging (fMRI) with a bilateral rest/finger-tapping paradigm, brain diffusion tensor imaging (DTI), voxel-based morphometry (VBM), and MR spectroscopy of the sensorimotor cortex were performed.A total of 92.3% of patients had more than one herniated disc. In the MRI, 33.33% presented signs of myelopathy. The mJOHA score was 13.03 ± 2.83. Compared with controls, DTI results showed significant lower FA values in Corpus callosum, both corticospinal tracts and middle cerebellar peduncles (p 0.05 corrected). Only in CS patients fMRI results showed activation in both globus pallidi, caudate nucleus, and left thalamus (p 0.001). Subject-specific activation of the BOLD signal showed in CS patients lower activation in the sensorimotor cortex and increased activation in both cerebellum hemispheres (p 0.05 corrected). VBM showed bilateral clusters of gray matter loss in the sensorimotor cortex and pulvinar nucleus (p 0.05 corrected) of CS patients. NAA/Cr was reduced in the sensorimotor cortex of CS patients (p 0.05). Linear discriminant and support vector machine analyses were able to classify 97% of CS patients with parameters obtained from the fMRI, DTI, and MRS results.CS may lead to distal brain damage affecting the white and gray matter of the sensorimotor cortex causing brain atrophy and functional adaptive changes.• This study suggests that patients with cervical spondylosis may present anatomical and functional adaptive changes in the brain. • Cervical spondylosis may lead to white matter damage, gray matter volume loss, and functional adaptive changes in the sensorimotor cortex. • The results reported in this work may be of value to better understand the effect of prolonged cervical spine compression in the brain.

We perform, in a manifestly $SO(n-1,1)$ [$SO(n)$] covariant fashion, the Hamiltonian analysis of general relativity in $n$ dimensions written as a constrained $BF$ theory. We solve the constraint on the $B$ field in a way naturally adapted to the foliation of the spacetime that avoids explicitly the introduction of the vielbein. This leads to a form of the action involving a presymplectic structure, which is reduced by doing a suitable parametrization of the connection and then, after integrating out some auxiliary fields, the Hamiltonian form involving only first-class constraints is obtained., Comment: It matches published version. arXiv admin note: text overlap with arXiv:2010.14526

In 2017, the WHO established that pituicytoma, granular cell tumour (GCT) and spindle cell oncocytoma (SCO) are posterior pituitary tumours (PPT). Recent data suggests that these tumours probably arise from the pituicytes and may constitute a spectrum of a unique histopathological entity. Our aim is to report the clinical findings and surgical outcomes of 16 patients with PPT. We also evaluated the tissue specimens available in light of current knowledge. Cross-sectional study with retrospective data. PPT were 7 pituicytomas, 3 GCT and 6 SCO. Patients mean age was 55 years old and 75% were female. Basal hormonal study showed hyperprolactinemia (43.7%) and hypopituitarism (37.5%). There was no case of diabetes insipidus (DI). MRI showed sellar/suprasellar masses with mean size of 19.7mm. PPT was not suspected in any patient. Fifteen patients underwent surgery and complications were common: 20% had perioperative bleeding (one patient died because of a massive haemorrhage), 57.1% hypopituitarism, 35.7% permanent DI and 21.4% underwent a second surgery. Pathological findings shown positivity for thyroid transcription factor 1, vimentin and negativity for cytokeratin and chromogranin A in all specimens evaluated. S100 protein was positive in 88.8% of tumours. Ki67 was ≥ 3% in 66.6% and ranged from 4-7% in SCO. PPT have similar histology, clinical features and are frequently misdiagnosed as nonfunctioning pituitary tumours. However, post-surgical complications including haemorrhage are common. A high clinical suspicion is needed to presume the diagnosis prior surgery and diminish the high morbidity of these tumours.

During the MILAGRO campaign, March 2006, eight-stage cut impactors were used to sample atmospheric particles at Tecamac (T1 supersite), towards the northeast edge of the Mexico City Metropolitan Area, collecting fresh local emissions and aged pollutants produced in Mexico City. Particle samples were analyzed to determine total mass concentrations of Ca2+, Mg2+, NH4 +, K+, Cl−, SO4 2−, and NO3 −. Average concentrations were 22.1 ± 7.2 μg m−3 for PM10 and 18.3 ± 6.2 μg m−3 for PM1.8. A good correlation between PM10 and PM1.8, without influence from wind patterns, indicates that local emissions are more important than the city’s pollution transported to the site, despite the fact that Tecamac is just 40 km away from Mexico City. A lack of diurnal patterns in the PM2.5/PM1.8 ratio supports this conclusion. The inorganic composition of particles suggests that vehicles, soil resuspension, and industries are the main pollutant sources. Finally, the particles were found to be neutralized, in agreement with observations in the Mexico City Metropolitan Area.

Clinical indications of brachytherapy in non-melanoma skin cancers, description of applicators and dosimetry recommendations are described based on the literature review, clinical practice and experience of Spanish Group of Brachytherapy and Spanish Society of Medical Physics reported in the XIV Annual Consensus Meeting on Non Melanoma Skin Cancer Brachytherapy held in Benidorm, Alicante (Spain) on October 21st, 2016. All the recommendations for which consensus was achieved are highlighted in blue. Regular and small surfaces may be treated with Leipzig, Valencia, flap applicators or electronic brachytherapy (EBT). For irregular surfaces, customized molds or interstitial implants should be employed. The dose is prescribed at a maximum depth of 3-4 mm of the clinical target volume/planning target volume (CTV/PTV) in all cases except in flaps or molds in which 5 mm is appropriate. Interstitial brachytherapy should be used for CTV/PTV > 5 mm. Different total doses and fraction sizes are used with very similar clinical and toxicity results. Hypofractionation is very useful twice or 3 times a week, being comfortable for patients and practical for Radiotherapy Departments. In interstitial brachytherapy 2 fractions twice a day are applied.

Habitat loss and degradation are main global threats to biodiversity, and land-use changes in agriculture-dominated landscapes are crucial for an important portion of biodiversity, especially in Europe. We evaluated the effects of land-use changes (1954–2012) on a threatened species, the ortolan bunting, in an agricultural area crucial for its conservation in Italy. We built a distribution model for ortolan bunting in current landscapes and then re-projected it to past scenarios (1954 and 1999–2000). We evaluated the most important land-use changes occurred and estimated their effects on habitat suitability. Bunting occurrence was mostly affected by the extent of grassland (positively; used as foraging/breeding ground), shrubland (quadratic effect; perches/shelter), forest and urbanized land (negatively), and by solar radiation (positively) and slope (quadratic), consistent with other studies carried out especially in southern Europe. The potential distribution of the species was much larger in the past: the estimated decline in suitable habitat is 44–72 % (since 1999–2000/1954), coherent with historical data suggesting strong decline and contraction. Changes in suitability (1954–2012) were mostly associated with changes in the cover of forest, vineyards and abandoned areas (negatively), and shrubland (positively). Land-use/land-cover changes are the main drivers of species occurrence and of habitat decline. The heterogeneous landscape of hilly/low-mountain sites in this area, characterized by a mix of habitats offering complementary resources to ortolan buntings and other species of conservation concern, is currently threatened by abandonment and intensification, but its maintenance may be promoted by a correct definition of Rural Development Programme measures.

The isothermal aging behavior of a cold-rolled precipitation hardening stainless steel has been studied at 723 K (450 °C) for holding times up to 72 hours. The precipitation hardening has been investigated using microhardness Vickers (Hv), thermoelectric power (TEP) measurements, and tensile testing. Microhardness compared to TEP measurements is more sensitive to detect the initial stages of aging. Two precipitation regimes have been observed: the first one related to the formation of Cu-clusters for aging times below 1 hour and a second one associated with formation of Ni-rich precipitates. The results show that the material exhibits an outstanding continuous age strengthening response over the aging time investigated, reaching a hardness of 710 ± 4 HV1 and an ultimate tensile strength (σ UTS) of 2.65 ± 0.02 GPa after 72 hours. Engineering stress-plastic strain curves reveal that the strength increases and the ductility decreases as the aging time increases. However, after prolonged holding times (24–72 hours) and, although small, a rise in both the strength and the total elongation is observed. The precipitation kinetics can be well predicted over the entire range of aging times by the Johnson–Mehl–Avrami–Kolmogorov (JMAK) equation. Finally, a reliable linear hardness-yield strength correlation has been found, which enables a rapid evaluation of the strength from bulk hardness measurements.

The increase of thermal efficiency in power plants has been the main driving force to develop Ferritic/Martensitic steels for structural applications capable of operating at 923 K (650 °C) and higher. It has been clarified in previous works that nano-sized precipitates and its distribution are the key factors controlling the stability of the microstructure at high operating temperatures. Based on the science of precipitate strengthening, the aim of this work is to optimize the thermo-mechanical treatment in a commercial creep-resistant steel (G91) to achieve a microstructure where MX precipitates present a suitable size and distribution. The alternative processing route proposed here allows gaining an increase up to 40 pct in yield strength at 973 K (700 °C) compared to the commercial steel. The results of small punch test carried out at room temperature showed that the improvement in strength was obtained without loss of ductility. This fact was attributed to a finer and more homogeneous dispersion of MX precipitates in comparison to the commercial steel., Authors acknowledge financial support to Spanish Ministerio de Economia y Competitividad (MINECO) through in the form of a Coordinate Project (MAT2013-47460-C5-1-P). Authors also acknowledge financial support to Comunidad de Madrid through DIMMAT-CM_S2013/MIT-2775 Project. J. Vivas acknowledges financial support in the form of a FPI Grant BES-2014-069863.

The aim of this study was to evaluate the effects of practical diets with different protein content on survival, growth, feed utilization and body composition of juvenile tench (Tinca tinca). A 90-day experiment was conducted with 6-month-old juveniles (34.35 mm total length, 0.411 g weight). Six practical diets differing in the protein level were tested: 40, 44, 48, 52, 56 or 60 %. Survival rates ranged from 96.7 to 100 %. The 52 % protein enabled the highest growth (55.49 mm total length, 2.11 g weight, 1.80 % day−1 specific growth rate) and the lowest feed conversion ratio (1.61) without significant differences (P > 0.05) from the 48 %. Protein productive value ranged from 15.64 to 22.01. The percentages of fish with visible deformities ranged from 1.1 to 4.4 %. The relationship among amino acid profiles of the diets, growth of juveniles, body composition and amino acid requirements of other fish species is discussed. Second-order polynomial regression analysis showed that the optimum dietary protein requirement for maximum growth of juvenile tench may be 52.7 %.

Pons herniation after cabergoline therapy for giant prolactinoma is a complication not documented in literature.We report a medium aged patient who developed secondary hemiparesis after 18 months of medical treatment. MRI revealed pons herniation into the clivus. There was improvement with conservative treatment. Secuencial MRIs are presented showing the tumor at the moment of the diagnosis, tumor shrinkage and pons herniation.Some studies have shown that a significant and rapid tumor shrinkage resulting from treatment with cabergoline can occur and it is thought that some complications are related with this tumor regression, as in the presented case.

The immune system (IS) represents the defence mechanism of higher level organisms to micro organismic threats. It is a very complex system, genuinely distributed and providing mechanisms of adaptation to unknown threats by means of the interaction among the heterogenous autonomous entities it is composed of. The most relevant features of the overall system, such as learning capabilities and the possibility to tackle unknown threats in any part of the body, are a consequence of these interactions. This paper describes how a Multi-Agent approach, and more precisely the situated cellular agents (SCA) model, can be applied to represent specific elements and mechanisms of the IS. After a brief description of the IS, a brief overview of possible modelling approaches will be given, then the SCA model will be introduced and exploited to model some elements and mechanisms of the IS. This work is one of the results of an interdisciplinary research that has involved immunologists of the Advanced Biotechnology Center of Genova and computer scientists of the University of Milan-Bicocca. © Springer Science+Business Media, Inc. 2006

Poster presentado en: ACNP (American College of Neuropsychopharmacology) 52nd Annual Conference, celebrada del 8 al 12 de diciembre de 2013 en Hollywood, Florida (Estados Unidos)

The progress of the martensite (a¢) to austenite (c) phase transformation has been thoroughly investigated at different temperatures during the continuous heating of a cold-rolled precipitation hardening metastable stainless steel at a heating rate of 0.1 K/s. Heat-treated samples have been characterized using different experimental complementary techniques: high-resolution dilatometry, magnetization, and thermoelectric power (TEP) measurements, micro-hardness- Vickers testing, optical/scanning electron microscopy, and tensile testing. The two-step transformation behavior observed is thought to be related to the presence of a pronounced chemical banding in the initial microstructure. This banding has been characterized using electron probe microanalysis. Unexpectedly, dilatometry measurements seem unable to locate the end of the transformation accurately, as this technique does not detect the second step of this transformation (last 20 pct of it). It is shown that once the starting (AS) and finishing (AF) transformation temperatures have been estimated by magnetization measurements, the evolution of the volume fractions of austenite and martensite can be evaluated by TEP or micro-hardness measurement quite reliably as compared to magnetization measurements. The mechanical response of the material after being heated to temperatures close to AS, AF, and (AF - AS)/2 is also discussed.

Psychiatric disorders represent a large economic burden in modern societies. However, pharmacological treatments are still far from optimal. Drugs used in the treatment of major depressive disorder (MDD) and anxiety disorders (selective serotonin [5-HT] reuptake inhibitors [SSRIs] and serotonin- noradrenaline reuptake inhibitors [SNRIs]) are pharmacological refinements of first-generation tricyclic drugs, discovered by serendipity, and show low efficacy and slowness of onset. Moreover, antipsychotic drugs are partly effective in positive symptoms of schizophrenia, yet they poorly treat negative symptoms and cognitive deficits. The present article reviews the neurobiological basis of 5-HT1A receptor (5-HT1A-R) function and the role of pre- and postsynaptic 5-HT1A-Rs in the treatment of MDD, anxiety and psychotic disorders. The activation of postsynaptic 5-HT1A-Rs in corticolimbic areas appears beneficial for the therapeutic action of antidepressant drugs. However, presynaptic 5-HT1A-Rs play a detrimental role in MDD, since individuals with high density or function of presynaptic 5-HT1A-Rs are more susceptible to mood disorders and suicide, and respond poorly to antidepressant drugs. Moreover, the indirect activation of presynaptic 5-HT1A-Rs by SSRIs/SNRIs reduces 5-HT neuron activity and terminal 5-HT release, thus opposing the elevation of extracellular 5-HT produced by blockade of the serotonin transporter (SERT) in the forebrain. Chronic antidepressant treatment desensitizes presynaptic 5-HT1A-Rs, thus reducing the effectiveness of the 5-HT1A autoreceptor-mediated negative feedback. The prevention of this process by the non-selective partial agonist pindolol accelerates clinical antidepressant effects. Two new antidepressant drugs, vilazodone (marketed in the USA) and vortioxetine (in development) incorporate partial 5-HT1A-R agonist properties with SERT blockade. Several studies with transgenic mice have also established the respective role of pre- and postsynaptic 5-HT1A-Rs in MDD and anxiety. In agreement with pharmacological studies, presynaptic and postsynaptic 5-HT1A-R activation appears necessary for anxiolytic and antidepressant effects, respectively, yet, neurodevelopmental roles for 5-HT1A-Rs are also involved. Likewise, the use of small interference RNA has enabled the showing of robust antidepressant-like effects in mice after selective knock-down of 5-HT1A autoreceptors. Postsynaptic 5-HT 1A-Rs in the prefrontal cortex (PFC) also appear important for the superior clinical effects of clozapine and other second-generation (atypical) antipsychotic drugs in the treatment of schizophrenia and related psychotic disorders. Despite showing a moderate in vitro affinity for 5-HT1A-Rs in binding assays, clozapine displays functional agonist properties at this receptor type in vivo. The stimulation of 5-HT1A-Rs in the PFC leads to the distal activation of the mesocortical pathway and to an increased dopamine release in PFC, an effect likely involved in the clinical actions of clozapine in negative symptoms and cognitive deficits in schizophrenia. The anxiolytic/antidepressant properties of 5-HT1A-R agonists in preclinical tests raised expectations enormously. However, these agents have achieved little clinical success, possibly due to their partial agonist character at postsynaptic 5-HT1A-Rs, together with full agonist properties at presynaptic 5-HT1A autoreceptors, as well as their gastrointestinal side effects. The partial 5-HT1A-R agonists buspirone, gepirone, and tandospirone are marketed as anxiolytic drugs, and buspirone is also used as an augmentation strategy in MDD. The development of new 5-HT1A-R agonists with selectivity for postsynaptic 5-HT 1A-Rs may open new perspectives in the field. © 2013 Springer International Publishing Switzerland.

11 páginas, 3 figuras, 3 tablas, Project AGL2008-04892-CO3-01 of the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I)and the Consolider-Ingenio 2010: CARNISENUSA (CSD 2007-00016) Ministerio de Ciencia y Técnologia. Spain

E2F1-3 proteins appear to have distinct roles in progenitor cells and in differentiating cells undergoing cell cycle exit. However, the function of these proteins in paradigms of terminal differentiation that involve continued cell division has not been examined. Using compound E2F1/E2F2-deficient mice, we have examined the effects of E2F1 and E2F2 loss on the differentiation and simultaneous proliferation of bone-marrow-derived cells toward the macrophage lineage. We show that E2F1/E2F2 deficiency results in accelerated DNA replication and cellular division during the initial cell division cycles of bone-marrow-derived cells, arguing that E2F1/E2F2 are required to restrain proliferation of pro-monocyte progenitors during their differentiation into macrophages, without promoting their cell cycle exit. Accelerated proliferation is accompanied by early expression of DNA replication and cell cycle regulators. Remarkably, rapid proliferation of E2F1/E2F2 compound mutant cultures is temporally followed by induction of a DNA damage response and the implementation of a p21(CIP1)-dependent senescence. We further show that differentiating E2F1/E2F2-knockout macrophages do not trigger a DNA damage response pathway in the absence of DNA replication. These findings underscore the relevance of E2F1 and E2F2 as suppressors of hematopoietic progenitor expansion. Our data indicate that their absence in differentiating macrophages initiates a senescence program that results from enforcement of a DNA damage response triggered by DNA hyper-replication.

Recent advances in intensive rearing of astacid juvenile crayfish have greatly improved the results. This challenges the current application possibilities of the studies performed previously, and new research on density is required. A 100-day experiment was carried out under controlled conditions to evaluate density effects on survival and growth rates of juvenile crayfish in optimal conditions of feeding. Juvenile stage 2 Pacifastacus leniusculus were stocked in fibreglass tanks (1 m2, 200 l water) at 20 ± 1°C and fed a dry diet for salmonids supplemented with restricted amounts of Artemia nauplii. Stocking densities were 100, 300, 600 and 1,000 crayfish m−2. Mean survival rate was reduced significantly with increased stocking density, ranging from 86.33% (100 m−2) to 39.13% (1,000 m−2). All checks showed that at the lowest initial density (100 m−2) animals grew significantly faster those at higher densities, recording a final carapace length of 15.28 mm and weight of 1.08 g. Among the treatments of 300, 600 and 1,000 m−2 no differences were found either in carapace length or in weight throughout the experimental period, with a final mean growth of 14 mm carapace length and 0.72 g weight. The final proportion of animals with chelae autotomy rose significantly with increasing stocking density, ranging from 14.44% (100 m−2) to 41.45% (1,000 m−2). This study shows that diet is a decisive factor for stocking successfully high densities under controlled conditions and provides useful information to set adequate densities in accordance with the production objectives.

A 120-day experiment was performed with 4-month-old juvenile tench [initial mean weight: 0.31 g; total length (TL): 32 mm] to evaluate live Artemia nauplii as supplement to a dry diet for salmonids. All groups received the dry diet. Five treatments, differing in the amount of supplemented Artemia, were tested: without supplement, 450, 900, and 1,800 nauplii g−1 initial fish biomass, and nauplii in excess. Groups that received Artemia supplement had significantly higher survival (between 89.4 and 98.7%) compared to those that received dry diet alone (49.2%), while among them there was no significant difference. Juvenile tench fed the dry diet supplemented with Artemia in excess had a specific growth rate (1.98), weight (3.40 g), and TL (63.90 mm) significantly higher than those in the rest of the treatments. The latter three features were not significantly different under limited co-feeding (450, 900, and 1,800 nauplii g−1 biomass) averaging 1.26 specific growth rate, 1.40 g weight, and 48.50 mm TL. Tench fed the dry diet alone grew significantly less than the rest. Thus, the drawbacks of feeding juvenile tench with dry foods originally formulated for other fish species can be overcome by providing a supplement of Artemia nauplii.

The development of artificial incubation techniques in astacid crayfish has attracted attention from scientists in many countries ever since the nineteenth century. It is only in the last few years that these techniques, along with studies on egg storage and transport, have provided reliable options for improving the reproductive phase in farming. The juveniles produced need to be reared until they reach a sufficient size both for restocking and for growing purposes. In view of the current level of knowledge of rearing juvenile astacids, two 80-day experiments were carried out under controlled conditions to compare the survival and growth of Stage 2 juvenile signal crayfish (Pacifastacus leniusculus) from two origins: maternal or artificial incubation. In the first experiment, three treatments were tested: juveniles from artificially incubated eggs with formaldehyde treatments, juveniles from maternal incubation and a mixture from both origins (50% each). Survival rates ranged from 87.8% to 93.3% with no significant differences among treatments. Crayfish from artificial incubation grew significantly faster (11.47 mm carapace length (CL), 373.80 mg weight) than crayfish from maternal incubation. In the second experiment, a bifactorial design included four treatments: the crayfish was derived from artificial or from maternal incubation and was fed once a day or twice a day. Final survival rates ranged from 68.89% to 77.78%, with no significant differences among treatments. Crayfish from artificial incubation grew significantly faster than crayfish from maternal incubation. The highest CL (14.54 mm) and weight (780.13 mg) were reached by the juveniles from artificial incubation that were fed once a day. No significant differences were found between the two feeding frequencies. Results showed that artificial incubation with formaldehyde treatments had no harmful effects and made it feasible to get a better performance from the juveniles obtained.

After artificial reproduction of tench, larvae must be maintained indoors, and studies on rearing conditions are needed, focussing on the reduction of labour and costs. Three experiments on larvae (5th day post-hatch) were conducted for 25 days using Artemia nauplii as the sole food in order to determine basic feeding and density conditions during the first rearing period. Tench were maintained in 25 l fibreglass tanks, supplied with an artesian water flow throughout of 0.2 l min−1. Water temperature was 22.5 ± 1°C, and the photoperiod was natural. Larvae fed on a restricted amount of nauplii reached high survival rates, even with the minimum of 50 nauplii larva−1 day−1. This amount of food may be sufficient at least for the first 25 days of exogenous feeding if fast growth is not the priority, and high densities can be maintained with good survival rates (over 90% up to 160 larvae l−1 and 77% with 320 larvae l−1). When food was supplied in excess once a day, high survival rates were achieved (91–97%), without differences among the densities tested. Animals at a density of 100 l−1 reached the highest length (15.57 mm) and individual weight (46.8 mg). This growth is greater than those reported in studies feeding several times a day. It could be deduced that, while live food remains available for tench, it is not necessary to feed so frequently. Considering the relationship among the initial number of animals, final survival and growth and ration supplied, the new data reported here are useful to establish suitable stocking densities under both culture and experimental conditions.

In two 120-day experiments, performed in the laboratory at 22°C, the effects of stocking density on the survival and growth of juvenile tench (Tinca tinca L.) were evaluated. Fish were kept in fibreglass tanks, supplied throughout with flow of artesian water, and fed a dry diet for salmonids, in excess, supplemented with restricted amounts of Artemia nauplii. In the first experiment four-month-old juveniles (0.31 ± 0.04 g and 32.00 ± 1.17 mm TL) were stocked at four densities—0.18, 0.88, 1.05, and 2.10 g l−1. Survival was high (>89%) for all treatments. Final densities ranged between 1.10 g l−1 (significantly lowest) and 10.46 g l−1 (significantly highest). The density increase was significantly higher (611%) for fish stocked at the lowest initial density (0.18 g l−1) than for fish stocked at 0.88, 1.05, and 2.10 g l−1, for which the density increase averaged 457%. In the second experiment, 4.5-month-old juveniles (0.58 ± 0.17 g and 39.54 ± 0.83 mm TL) were stocked at three densities—1.05, 3.00, and 4.00 g l−1. Survival was high (>96%) for all treatments. Final densities ranged between 4.08 and 16.53 g l−1 and were significantly higher for greater initial densities. The density increase was greatest (413%) for fish stocked at the highest density (4 g l−1) and was not significantly different for fish stocked at 1.05 and 3 g l−1. Considering all the densities in the two experiments, for stocking at 4 g l−1 the final density was 15 times higher than that reached after stocking at 0.18 g l−1, without harmful effects on survival and growth. This final density (equivalent to 16.53 kg m−3) is in the range recommended for other fish species in this period under intensive conditions.

The aim of this work was to evaluate the reproductive potential of the signal crayfish (Pacifastacus leniusculus Dana) in the second cycle under culture conditions. The experiment was carried out using 5,653 animals placed in six earthen ponds in August. Three treatments were performed, each in two ponds: breeder reuse (males and females used in the former reproductive cycle), female reuse (new males from the wild and females used in the former reproductive cycle) and new breeders (males and females from the wild). In April, close to hatching, egg-bearing females were transferred to the hatchery. Mortality of the reused breeders (around 30% of females and 41.4% of males) was significantly higher than that of the new breeders (11.4% of females and around 19.5% of males). The proportion of berried females close to hatching was significantly higher for the new ones (77.4% of the initial number), and the percentage of new females with a large quantity of eggs (63.6%) was higher than that of the reused females (25.6 and 20.9%). Differences among the percentages of females without eggs in the new breeders (11.2%) and the rest of the treatments (30.7 and 39.6%) were significant. The reproductive capacity of reused females was not improved by providing new males. Considering the number of females initially stocked into ponds, mean yield per new female was greater than that of the reused females, mainly due to the higher mortality recorded in the reused broodstock. Although the yield that can be obtained using the same breeders in two reproductive cycles drops in the second one, the production was not negligible.

Despite the vast amount of research on schizophrenia and depression in the past two decades, there have been few innovative drugs to treat these disorders. Precompetitive research collaborations between companies and academic groups can help tackle this innovation deficit, as illustrated by the achievements of the IMI-NEWMEDS consortium.

Soft tissue tumors in the upper extremity can present challenging problems. Intravascular papillary endothelial hyperplasia may be misdiagnosed as angiosarcoma by inexperienced surgeons and pathologists. Four cases of this infrequent tumor in its most frequent location, the hand, are presented. Although the characteristic microscopic appearance confirms the definitive diagnosis, the clinical history and behavior may help to identify the lesion. We describe the clinical and pathological features of these four vascular hand tumors. It must be recognized as being a benign lesion to avoid unnecessary treatment. However, the importance of wide excision to reduce the risk of recurrence is stressed since this occurred in two of the four cases presented.