Primitive neuroectodermal kidney tumor

To the Editor: Primitive neuroectodermal tumors (PNET) and Ewing sarcoma (ES) belong to a group of neoplasms de®ned by neuroectodermal differentiation and a characteristic cytogenetic translocation, t(11;22) (q24;q12) or gene rearrangements between chromosomes 21 and 22 [1]. They are generally aggressive tumors that present as metastatic disease in nearly 50% of the cases. ES is frequently a bone disease, whereas PNET can occur in bones, soft tissues, or any other site. Renal PNETs are extremely rare, with only a few cases reported [2]. We here record an adult with renal PNET and bone metastases at diagnosis. Because these tumor can also be found in children [3] our experience may therefore be helpful to pediatric oncologist

Switching from natalizumab to fingolimod: an observational study

Background – Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known. Aims of the study – We report on clinical and MRI data and patient safety in a group of relapsing–remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks. Methods – The test for JC virus antibodies was performed in 18 relapsing–remitting multiple sclerosis patients who were being treated with natalizumab for more than 1 year. Eight seropositive patients switched to fingolimod while the seronegative patients continued with natalizumab. Results – After switching to fingolimod, five of eight patients (63%) experienced clinical relapses, and MRI activity was detected in six of eight patients (75%). Neither clinical relapses nor MRI activity was observed in the patients who continued with natalizumab. No serious adverse effects were detected. Conclusions – Natalizumab is an effective treatment for relapsing–remitting multiple sclerosis, but its discontinuation continues to be a complex problem. All of the therapies tried thus far, including fingolimod, have been unable to control the reactivation of the disease. Further studies addressing alternative therapies after natalizumab discontinuation are necessary

Density dependence in marine protected populations: a review

The cessation or reduction of fishing in marine protected areas (MPAs) should promote an increase in abundance and mean size and age of previously exploited populations. Thus density-dependent changes in life-history characteristics should occur when populations are allowed to recover in MPAs. In this review, we synthesize the existing information on resource limitation in marine ecosystems, density-dependent changes in life-history traits of exploited populations and evidence for biomass export from MPAs. Most evidence for compensatory changes in biological variables has been derived from observations on populations depleted by high fishing mortality or on strong year classes, but these changes are more evident in juveniles than in adults and in freshwater rather than in marine systems. It is unclear if adults of exploited marine populations are resource limited. This may suggest that exploited populations are controlled mainly by density-independent processes, which could be a consequence of the depleted state of most exploited populations. MPAs could be a useful tool for testing these hypotheses. If we assume that resources become limiting inside MPAs, it is plausible that, if suitable habitats exist, mobile species will search for resources outside of the MPAs, leading to export of biomass to areas which are fished. However, it is not possible to establish from the available data whether this export will be a response to resource limitation inside the MPAs, the result of random movements across MPA boundaries or both. We discuss the implications of this process for the use of MPAs as fisheries management tools.Financial support was provided by the EU CEC DGXII – MAST III contract number: MAS3-ct97-0155

Effectiveness of Fingolimod versus Natalizumab as Second-Line Therapy for Relapsing-Remitting Multiple Sclerosis in Spain: Second-Line GATE Study

Background: There is a lack of head-to-head studies comparing the efficacy of fingolimod (FIN) and natalizumab (NTZ) as second-line therapy for relapsing-remitting multiple sclerosis (RRMS). Methods: Multicenter, observational study, in which, information of 388 patients randomly selected and treated with FIN or NTZ in routine clinical practice was retrospectively collected with the main objective of comparing the annualized relapse rate (ARR) over the first year, after FIN or NTZ treatment initiation. Results: Mean ARR during the first year of treatment was 0.28 in FIN group and 0.12 in NTZ group (p = 0.0064); nevertheless, the difference between groups lost statistical significance when the propensity score analysis was performed. Time to disability -progression was similar in both treatment groups (12.3 +/- 6.7 months in FIN, and 12.8 +/- 0.1 months in NTZ; p = 0.4654). Treatment persistence after the first year of treatment was higher in patients treated with FIN (95%) than in those treated with NTZ (84%; p = 0.0014). Conclusions: After 12 months of treatment, both FIN and NTZ reduced the ARR, but ARR percent reduction was significantly higher with NTZ. Treatment persistence was higher in patients receiving FIN

Variables psicológicas implicadas en la actitud e iniciativa emprendedora

Identificar variables individuales relacionadas con la iniciativa emprendedora y el fomento de competencias transversales relacionadas con la misma, supone un desafío en la investigación actual sobre emprendimiento. El proyecto titulado Variables psicológicas implicadas en la actitud e iniciativa emprendedora, realizado bajo el programa Innova Docencia promovido por el Vicerrectorado de Calidad de la UCM en la convocatoria 2016-2017, ha tenido por objetivo analizar y evaluar variables psicológicas relacionadas con emprendimiento que presentan una muestra de estudiantes de la Universidad Complutense de Madrid. En dicho estudio han participado 1222 estudiantes de la UCM correspondientes a 27 titulaciones: 14 de Grado, 2 de Dobles Grados, y 11 de Máster. El 28,6% de la muestra fueron hombres y el 71% fueron mujeres. La media de edad fue de 20,43 años. El equipo investigador estuvo compuesto por 40 personas: 25 PDI de la UCM, 2 PAS, 8 alumnos y alumnas, 1 técnico, y 4 PDI de las universidades de Castilla-La Mancha (UCLM), UNED, Carlos III de Madrid (UC3M), y Alcalá de Henares (UAH). El PDI de la UCM correspondía a las siguientes facultades: Psicología (7), Ciencias de la Documentación (3), Ciencias Económicas y Empresariales (6), Ciencias Políticas y Sociología (3), Comercio (1), Trabajo Social (1), Ciencias Biológicas (2), Informática (1), y Bellas Artes (1). Un equipo UCM perteneciente a 9 facultades, que representó a 13 departamentos y a todas las áreas de conocimiento. La metodología empleada consistió en un cuestionario que evaluaba los siguientes aspectos: datos sociodemográficos, actitud emprendedora, y las variables psicológicas: personalidad, inteligencia emocional, resolución de problemas y tolerancia a la ambigüedad. Se optó por instrumentos estandarizados, con buenas características psicométricas de fiabilidad y validez que permitieran obtener resultados robustos, con amplia evidencia empírica y que evaluaban adecuadamente variables que la literatura ha relacionado con la actitud e iniciativa emprendedora. Además todos ellos se han utilizado en investigaciones relacionadas con emprendimiento, lo que aumentó la validez externa. Se ha analizado la iniciativa emprendedora desde el punto de vista de los estudiantes y también teniendo en cuenta variables del entorno familiar y personal. Los resultados nos muestran que son las variables psicológicas de extraversión, reparación emocional y estrategias de resolución de problemas las que predicen la iniciativa emprendedora. Los estudiante que compaginan estudios y trabajo tienen una mayor iniciativa emprendedora, y aquellos cuyos padres y/o pareja desarrollan su actividad laboral como autónomos. Se presentan datos por titulación académica, sexo, actividad laboral de los padres y compaginar estudios y trabajo. Se muestran datos de todas las variables psicológicas por titulación académica, y una comparativa de dichas variables entre los universitarios, un grupo de estudiantes de Formación Profesional (FP) y una muestra de emprendedores reales. Los resultados obtenidos son relevantes para tomar decisiones orientadas a la mejora de la actitud, iniciativa y comportamiento emprendedor. Permitirán el diseño y ejecución de actividades académicas para sensibilizar a los estudiantes en la cultura emprendedora, y formar en competencias transversales, cada vez más demandadas, para mejorar la empleabilidad y competitividad como claves para el crecimiento de nuestra sociedad

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Benign hereditary chorea: Clinical features and long-term follow-up in a Spanish family

3 páginas, 1 figura, 1 tabla y en la versión electrónica 1 videoThis project was supported in part by Generalitat Valenciana (ACOMP/2012/024) and MICINN (SAF2009-10434)Peer reviewe

Mutation prevalence of cerebral cavernous malformation genes in Spanish patients.

Journal Article; Research Support, Non-U.S. Gov't;OBJECTIVE To study the molecular genetic and clinical features of cerebral cavernous malformations (CCM) in a cohort of Spanish patients. METHODS We analyzed the CCM1, CCM2, and CCM3 genes by MLPA and direct sequencing of exons and intronic boundaries in 94 familial forms and 41 sporadic cases of CCM patients of Spanish extraction. When available, RNA studies were performed seeking for alternative or cryptic splicing. RESULTS A total of 26 pathogenic mutations, 22 of which predict truncated proteins, were identified in 29 familial forms and in three sporadic cases. The repertoire includes six novel non-sense and frameshift mutations in CCM1 and CCM3. We also found four missense mutations, one of them located at the third NPXY motif of CCM1 and another one that leads to cryptic splicing of CCM1 exon 6. We found four genomic deletions with the loss of the whole CCM2 gene in one patient and a partial loss of CCM1and CCM2 genes in three other patients. Four families had mutations in CCM3. The results include a high frequency of intronic variants, although most of them localize out of consensus splicing sequences. The main symptoms associated to clinical debut consisted of cerebral haemorrhage, migraines and epileptic seizures. The rare co-occurrence of CCM with Noonan and Chiari syndromes and delayed menarche is reported. CONCLUSIONS Analysis of CCM genes by sequencing and MLPA has detected mutations in almost 35% of a Spanish cohort (36% of familial cases and 10% of sporadic patients). The results include 13 new mutations of CCM genes and the main clinical symptoms that deserves consideration in molecular diagnosis and genetic counselling of cerebral cavernous malformations.This work has been supported by grants CP10/00526 (Instituto de Salud Carlos III, Spain) and P07-CVI-02790 (Junta de Andalucía, Spain) and José Luis Castaño Foundation.Ye