TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs.

Clinical, pathological and genetic examination revealed an as yet uncharacterized juvenile-onset neuroaxonal dystrophy (NAD) in Spanish water dogs. Affected dogs presented with various neurological deficits including gait abnormalities and behavioral deficits. Histopathology demonstrated spheroid formation accentuated in the grey matter of the cerebral hemispheres, the cerebellum, the brain stem and in the sensory pathways of the spinal cord. Iron accumulation was absent. Ultrastructurally spheroids contained predominantly closely packed vesicles with a double-layered membrane, which were characterized as autophagosomes using immunohistochemistry. The family history of the four affected dogs suggested an autosomal recessive inheritance. SNP genotyping showed a single genomic region of extended homozygosity of 4.5 Mb in the four cases on CFA 8. Linkage analysis revealed a maximal parametric LOD score of 2.5 at this region. By whole genome re-sequencing of one affected dog, a perfectly associated, single, non-synonymous coding variant in the canine tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene affecting a highly conserved region was detected (c.4009C>T or p.R1337W). This canine NAD form displays etiologic parallels to an inherited TECPR2 associated type of human hereditary spastic paraparesis (HSP). In contrast to the canine NAD, the spinal cord lesions in most types of human HSP involve the sensory and the motor pathways. Furthermore, the canine NAD form reveals similarities to cases of human NAD defined by widespread spheroid formation without iron accumulation in the basal ganglia. Thus TECPR2 should also be considered as candidate gene for human NAD. Immunohistochemistry and the ultrastructural findings further support the assumption, that TECPR2 regulates autophagosome accumulation in the autophagic pathways. Consequently, this report provides the first genetic characterization of juvenile canine NAD, describes the histopathological features associated with the TECPR2 mutation and provides evidence to emphasize the association between failure of autophagy and neurodegeneration.

The Political Candidacy of EU Migrants in their European Countries of Residence. The Case of British and Romanians Standing in Spanish Local Elections

What explains the variation in how European citizens of diverse origins are politically incorporated in the member states of residence? This paper argues that immigrant groups’ status in the host society plays an important role in political party responses to immigrants’ political participation. Drawing on the case of Romanian and British candidacies in the Spanish local elections from 2011, the paper finds that the level of competition between parties is the key mechanism for incorporating candidates from a positively/neutrally perceived group. Instead, a greater level of ethnic diversity encourages the incorporation of candidates from the negatively perceived group. To demonstrate this, the paper uses an original data-set with the Romanian and British candidates in a large number of Spanish localities.

Dose-painting intensity-modulated proton therapy for intermediate- and high-risk meningioma.

BACKGROUND Newly diagnosed WHO grade II-III or any WHO grade recurrent meningioma exhibit an aggressive behavior and thus are considered as high- or intermediate risk tumors. Given the unsatisfactory rates of disease control and survival after primary or adjuvant radiation therapy, optimization of treatment strategies is needed. We investigated the potential of dose-painting intensity-modulated proton beam-therapy (IMPT) for intermediate- and high-risk meningioma. MATERIAL AND METHODS Imaging data from five patients undergoing proton beam-therapy were used. The dose-painting target was defined using [68]Ga-[1,4,7,10-tetraazacyclododecane tetraacetic acid]- d-Phe(1),Tyr(3)-octreotate ([68]Ga-DOTATATE)-positron emission tomography (PET) in target delineation. IMPT and photon intensity-modulated radiation therapy (IMRT) treatment plans were generated for each patient using an in-house developed treatment planning system (TPS) supporting spot-scanning technology and a commercial TPS, respectively. Doses of 66 Gy (2.2 Gy/fraction) and 54 Gy (1.8 Gy/fraction) were prescribed to the PET-based planning target volume (PTVPET) and the union of PET- and anatomical imaging-based PTV, respectively, in 30 fractions, using simultaneous integrated boost. RESULTS Dose coverage of the PTVsPET was equally good or slightly better in IMPT plans: dose inhomogeneity was 10 ± 3% in the IMPT plans vs. 13 ± 1% in the IMRT plans (p = 0.33). The brain Dmean and brainstem D50 were small in the IMPT plans: 26.5 ± 1.5 Gy(RBE) and 0.002 ± 0.0 Gy(RBE), respectively, vs. 29.5 ± 1.5 Gy (p = 0.001) and 7.5 ± 11.1 Gy (p = 0.02) for the IMRT plans, respectively. The doses delivered to the optic structures were also decreased with IMPT. CONCLUSIONS Dose-painting IMPT is technically feasible using currently available planning tools and resulted in dose conformity of the dose-painted target comparable to IMRT with a significant reduction of radiation dose delivered to the brain, brainstem and optic apparatus. Dose escalation with IMPT may improve tumor control and decrease radiation-induced toxicity.

A potential case of attitude change: The Spanish spoken in the city of Malaga and used on social network sites

The Spanish spoken in the city of Malaga, as Andalusian Spanish in general, was in the past often times considered an incorrect, low prestige variety of Spanish which was strongly associated with the poor, rural, backward South of Spain. This southern Spanish variety is easily recognised because of its innovative phonetic features that diverge from the national standard, even though in the past years in the case of some features a convergence to the standard could be observed. Despite its low prestige the local variety of Spanish is quite often used on social network sites, where it is considered as urban, fashion and cool. Thus, this paper aims at analysing whether the Spanish used in the city of Malaga is undergoing an attitude change. The study draws on naturally occurring speech, data extracted from Facebook and a series of questionnaires about the salience, attitude and perception of the local variety of Spanish. The influence of the social factors age and gender is analysed, since they are both known to play a crucial role in many instances of language change. The first is of special interest, as during the Franco dictatorship dialect use was not accepted in schools and in the media. Results show that, on the one hand, people from Malaga hold a more positive attitude towards non-standard features used on social network sites than in spoken language. On the other hand, young female users employ most non-standard features online and unsurprisingly have an extremely positive attitude towards this use. However, in spoken Spanish the use and attitude of some features is led by men and speakers educated during the Franco dictatorship, while other features, such as elision of intervocalic /d/, elision of final /ɾ/, /l/ and /d/ and ceceo, are predominantly employed by and younger speakers and women. These features are considered as salient in the local variety and work as local identity markers.