Nouvelles stratégies thérapeutiques en oncologie ophtalmo-pédiatrique [New strategies in pediatric ophthalmic oncology]

Le rétinoblastome représente 11% de tous les cancers apparaissant pendant la première année de vie. Pour éviter les effets secondaires de la chimiothérapie systémique ou de la radiothérapie externe, de nouveaux médicaments et de nouvelles techniques de traitement focalisé ont été développés. Des voies d'administration telles la voie périoculaire (topotécan) ou la voie artérielle ophtalmique directe (carboplatine) sont utilisées aujourd'hui dans certains cas résistants. La radiothérapie actuelle, appliquée exclusivement en deuxième intention, fait appel également à des techniques ciblées, permettant d'éviter les tissus sains et de réduire le risque de cancers radio-induits non oculaires. La radiothérapie stéréotaxique conformationnelle ou conformale et la proton-thérapie font ainsi partie du nouvel arsenal thérapeutique du rétinoblastome. Retinoblastoma represents 11% of all cancers during the first year of life. New drugs and focal treatments have been developed in order to avoid the side effects of systemic chemotherapy and external radiotherapy. New targeted and local administration strategies such as periocular chemotherapy (topotecan) or direct ophthalmic artery delivery (carboplatin), are already used today in selected resistant cases. Radiotherapy, presently indicated only as a second-line treatment, is also subject to new techniques, targeting tumors more closely to avoid involving healthy tissue and reduce the risk of radio-induced nonocular tumors. Stereotactic conformal radiotherapy and proton therapy may thus be included in the new range of treatment methods in retinoblastoma

Origen i diversificació de les comunitats de rèptils dels deserts del Nord d’Àfrica i Aràbia: els paràsits com a eines filogenètiques

Els deserts constitueixen aproximadament un terç de la superfície terrestre i estan caracteritzats per la seva aridesa extrema. Els Sàhara, la zona àrida més gran del Nord d’Àfrica és, amb diferencia, el desert més gran del mon. Ocupa una extensió de més de 9 milions de kilòmetres quadrats, expandint-se 5500 km a través del nord d’Àfrica, des de l’oceà Atlàntic fins el mar Roig. El desert d’Aràbia es troba a l’est del Sàhara i és aproximadament una octava part més petit. Tot i el seu clima tan extrem, les flores i faunes dels deserts acostumen a ser relativament riques, el que fa que ens preguntem com aquestes biotes han estat adquirides i com es mantenen. En aquest projecte utilitzem els rèptils com a model d’estudi, un dels habitants més comuns dels deserts. El propòsit d’aquest projecte era utilitzar filogènies moleculars de diversos taxons de rèptils dels deserts del nord d’Àfrica i Aràbia per respondre Quan i Com els deserts han adquirit la seva fauna de rèptils endèmica (origen i diversificació), i de quina manera aquestes faunes s’han mantingut fins ara (adaptació). Però més enllà de les dades morfològiques i les eines de filogènia molecular, els paràsits representen una alternativa excitant i innovadora dins del camp de la biologia evolutiva. En aquest sentit, aquest projecte de beca proposava anar més lluny i utilitzar els paràsits com a eina (biological tags) per millor entendre l’historia evolutiva dels seus hostes en base a una aproximació biogeogràfica i co-evolutiva. Els objectius durant aquest primer any de projecte han sigut: 1) Estudiar l’origen i diversificació de la fauna de rèptils endèmica dels deserts del Sàhara i Aràbia, 2) caracteritzar la comunitat d’ecto- haemoparàsits de les espècies d’estudi, 3) posar a punt un estudi comparatiu de la filogeografia i estructuració genètica d’hostes i paràsits.

Developing methodologies to allow the robust prediction dynamic context dominated by perturbations

El principal objectiu del projecte era desenvolupar millores conceptuals i metodològiques que permetessin una millor predicció dels canvis en la distribució de les espècies (a una escala de paisatge) derivats de canvis ambientals en un context dominat per pertorbacions. En un primer estudi, vàrem comparar l'eficàcia de diferents models dinàmics per a predir la distribució de l'hortolà (Emberiza hortulana). Els nostres resultats indiquen que un model híbrid que combini canvis en la qualitat de l'hàbitat, derivats de canvis en el paisatge, amb un model poblacional espacialment explícit és una aproximació adequada per abordar canvis en la distribució d'espècies en contextos de dinàmica ambiental elevada i una capacitat de dispersió limitada de l'espècie objectiu. En un segon estudi abordarem la calibració mitjançant dades de seguiment de models de distribució dinàmics per a 12 espècies amb preferència per hàbitats oberts. Entre les conclusions extretes destaquem: (1) la necessitat de que les dades de seguiment abarquin aquelles àrees on es produeixen els canvis de qualitat; (2) el biaix que es produeix en la estimació dels paràmetres del model d'ocupació quan la hipòtesi de canvi de paisatge o el model de qualitat d'hàbitat són incorrectes. En el darrer treball estudiarem el possible impacte en 67 espècies d’ocells de diferents règims d’incendis, definits a partir de combinacions de nivells de canvi climàtic (portant a un augment esperat de la mida i freqüència d’incendis forestals), i eficiència d’extinció per part dels bombers. Segons els resultats dels nostres models, la combinació de factors antropogènics del regim d’incendis, tals com l’abandonament rural i l’extinció, poden ser més determinants per als canvis de distribució que els efectes derivats del canvi climàtic. Els productes generats inclouen tres publicacions científiques, una pàgina web amb resultats del projecte i una llibreria per a l'entorn estadístic R.

Probabilistically analysable real-time systems (PROARTIS)

Critical real-time ebedded (CRTE) Systems require safe and tight worst-case execution time (WCET) estimations to provide required safety levels and keep costs low. However, CRTE Systems require increasing performance to satisfy performance needs of existing and new features. Such performance can be only achieved by means of more agressive hardware architectures, which are much harder to analyze from a WCET perspective. The main features considered include cache memòries and multi-core processors.Thus, althoug such features provide higher performance, corrent WCET analysis methods are unable to provide tight WCET estimations. In fact, WCET estimations become worse than for simple rand less powerful hardware. The main reason is the fact that hardware behavior is deterministic but unknown and, therefore, the worst-case behavior must be assumed most of the time, leading to large WCET estimations. The purpose of this project is developing new hardware designs together with WCET analysis tools able to provide tight and safe WCET estimations. In order to do so, those pieces of hardware whose behavior is not easily analyzable due to lack of accurate information during WCET analysis will be enhanced to produce a probabilistically analyzable behavior. Thus, even if the worst-case behavior cannot be removed, its probabilty can be bounded, and hence, a safe and tight WCET can be provided for a particular safety level in line with the safety levels of the remaining components of the system. During the first year the project we have developed molt of the evaluation infraestructure as well as the techniques hardware techniques to analyze cache memories. During the second year those techniques have been evaluated, and new purely-softwar techniques have been developed.

Discovering the campus together: a mobile and computer-based learning experience

One of the most relevant difficulties faced by first-year undergraduate students is to settle into the educational environment of universities. This paper presents a case study that proposes a computer-assisted collaborative experience designed to help students in their transition from high school to university. This is done by facilitating their first contact with the campus and its services, the university community, methodologies and activities. The experience combines individual and collaborative activities, conducted in and out of the classroom, structured following the Jigsaw Collaborative Learning Flow Pattern. A specific environment including portable technologies with network and computer applications has been developed to support and facilitate the orchestration of a flow of learning activities into a single integrated learning setting. The result is a Computer-Supported Collaborative Blended Learning scenario, which has been evaluated with first-year university students of the degrees of Software and Audiovisual Engineering within the subject Introduction to Information and Communications Technologies. The findings reveal that the scenario improves significantly students’ interest in their studies and their understanding about the campus and services provided. The environment is also an innovative approach to successfully support the heterogeneous activities conducted by both teachers and students during the scenario. This paper introduces the goals and context of the case study, describes how the technology was employed to conduct the learning scenario, the evaluation methods and the main results of the experience.

Continuing declines in cancer mortality in the European Union

BACKGROUND: From 1988 to 1997 age-standardised total cancer mortality rates in the European Union (EU) fell by around 9% in both sexes. Available cancer mortality data in Europe up to 2002 allow a first check of the forecast of further declines in cancer mortality. PATIENTS AND METHODS: We considered trends in age-standardised mortality from major cancer sites in the EU during the period 1980-2002. RESULTS: For men, total cancer mortality, after a peak of 191.1/100,000 in 1987 declined to 177.8 in 1997 (-7%), and to 166.5 in 2002. Corresponding figures for females were 107.9/100,000, 100.5 and 95.2, corresponding to falls of 7% from 1987 to 1997, and to 5% from 1997 to 2002. Over the last 5 years, lung cancer declined by 1.9% per year in men, to reach 44.4/100,000, but increased by 1.7% in women, to reach 11.4. In 2002, for the first year, lung cancer mortality in women was higher than that for intestinal cancer (11.1/100,000), and lung cancer became the second site of cancer deaths in women after breast (17.9/100,000). From 1997 to 2002, appreciable declines were observed in mortality from intestinal cancer in men (-1.6% per year, to reach 18.8/100,000), and in women (-2.5%), as well as for breast (-1.7% per year) and prostate cancer (-1.4%). CONCLUSIONS: Despite the persisting rises in female lung cancer, the recent trends in cancer mortality in the EU are encouraging and indicate that an 11% reduction in total cancer mortality from 2000 to 2015 is realistic and possible.

The effects of a universal child benefit

I study the impact of a universal child benefit on fertility and family well-being. I exploitthe unanticipated introduction of a new, sizeable, unconditional child benefit in Spain in2007, granted to all mothers giving birth on or after July 1, 2007. The regressiondiscontinuity-type design allows for a credible identification of the causal effects. I find thatthe benefit did lead to a significant increase in fertility, as intended, part of it coming froman immediate reduction in abortions. On the unintended side, I find that families whoreceived the benefit did not increase their overall expenditure or their consumption ofdirectly child-related goods and services. Instead, eligible mothers stayed out of the laborforce significantly longer after giving birth, which in turn led to their children spending lesstime in formal child care and more time with their mother during their first year of life. Ialso find that couples who received the benefit were less likely to break up the year afterhaving the child, although this effect was only short-term. Taken together, the resultssuggest that child benefits of this kind may successfully increase fertility, as well asaffecting family well-being through their impact on maternal time at home and familystability.

Fauna de Muscidae (Diptera) em três localidades do Estado do Paraná, Brasil, capturada por armadilha Malaise

During two years, from August 1986 to July 1988, the entomofauna of some preserved areas of Parana State, southern Brazil, was sampled in a project called "Levantamento da Fauna Entomológica no Estado do Paraná (PROFAUPAR)". Specimens of Muscidae (Diptera) were sorted out from the material collected using Malaise traps in three of the eight sites sampled (Colombo, Ponta Grossa and Guarapuava) in the first year (August 1986 to July 1987). A total of 7,014 specimens of Muscidae was captured and 91 species were identified. Neodexiopsis flavipalpis Albuquerque was the most abundant species in Ponta Grossa (672 specimens) and in Guarapuava (332 specimens). For Colombo, the most abundant species was Neodexiopsis vulgaris Couri & Albuquerque (172 specimens). The highest richness of species and abundance were observed in Ponta Grossa (77 and 3,559 respectively). The total number of specimens and means values of capture were analyzed. Indices of diversity and evenness were used to discuss richness and dominance of species in each locality. Besides using ecological indices, species richness estimators were also used.

Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.11.

Infantile spasms (IS) is the most severe and common form of epilepsy occurring in the first year of life. At least half of IS cases are idiopathic in origin, with others presumed to arise because of brain insult or malformation. Here, we identify a locus for IS by high-resolution mapping of 7q11.23-q21.1 interstitial deletions in patients. The breakpoints delineate a 500 kb interval within the MAGI2 gene (1.4 Mb in size) that is hemizygously disrupted in 15 of 16 participants with IS or childhood epilepsy, but remains intact in 11 of 12 participants with no seizure history. MAGI2 encodes the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 that interacts with Stargazin, a protein also associated with epilepsy in the stargazer mouse.

When performance-approach goals predict academic achievement and when they do not: A social value approach

Research on achievement goal promotion at University has shown that performance-approach goals are perceived as a means to succeed at University (high social utility) but are not appreciated (low social desirability). We argue that such a paradox could explain why research has detected that performance-approach goals consistently predict academic grades. First-year psychology students answered a performance-approach goal scale with standard, social desirability and social utility instructions. Participants' grades were recorded at the end of the semester. Results showed that the relationship between performance-approach goals and grades was inhibited by the increase of these goals' social desirability and facilitated by the increase of their social utility, revealing that the predictive validity of performance-approach goals depend on social value.

The effect of treatment with calcitonin on vertebral fracture rate in osteoporosis.

The efficacy of treatments for osteoporosis does not become evident when evaluated by fracture incidence (FI). Vertebral FI decreased in all controlled studies on calcitonin, but not significantly. Small sample sizes and short periods of treatment may have masked a possible therapeutic benefit, but longer, controlled studies with sodium fluoride or etidronate in larger groups of patients also failed to show a decrease in FI. The present analysis of nine published, therapeutic studies which indicate the FI per year and the initial prevalence of vertebral fractures, examines the question of whether the initial prevalence of fractures has an effect on the subsequent incidence of new fractures and whether the therapeutic effects have to be evaluated as a function of the initial prevalence of fractures. Bearing in mind the differences in roentgenological evaluation and in the size and quality of the various studies, the analysis revealed (1) that in the control groups there was a higher FI in patients with more than three vertebral fractures at baseline (estimated odds ratio (OR) = 49, p = 0.011); (2) that a similar trend, although not statistically significant, was observed in treated patients; (3) that the groups of control patients treated for more than 1 year showed in general an increase in FI beyond the first year and that the reverse was true in treated patients. In conclusion, failure to allow for the initial prevalence of vertebral fractures at the individual level in therapeutic trials of calcitonin to treat osteoporosis and prevent new fractures might have contributed to the absence of a demonstrable benefit of the treatment in those studies.

Characterization of CD4+ CD25+ T cells in solid organ transplant recipients

Although important progresses have been achieved in the therapeutic management of transplant recipients, acute and chronic rejections remain the leading causes of premature graft loss after solid organ transplantation. This, together with the undesirable side effects of immunosuppressive drugs, has significant implications for the long-term outcome of transplant recipients. Thus, a better understanding of the immunological events occurring after transplantation is essential. The immune system plays an ambivalent role in the outcome of a graft. On one hand, some T lymphocytes with effector functions (called alloreactive) can mediate a cascade of events eventually resulting in the rejection, either acute or chronic, of the grafted organ ; on the other hand, a small subset of T lymphocytes, called regulatory T cells, has been shown to be implicated in the control of these harmful rejection responses, among other things. Thus, we focused our interest on the study of the balance between circulating effectors (alloreactive) and regulatory T lymphocytes, which seems to play an important role in the outcome of allografts, in the context of kidney transplantation. The results were correlated with various variables such as the clinical status of the patients, the immunosuppressive drugs used as induction or maintenance agents, and past or current episodes of rejection. We observed that the percentage of the alloreactive T lymphocyte population was correlated with the clinical status of the kidney transplant recipients. Indeed, the highest percentage was found in patients suffering from chronic humoral rejection, whilst patients on no or only minimal immunosuppressive treatment or on sirolimus-based immunosuppression displayed a percentage comparable to healthy non-transplanted individuals. During the first year after renal transplantation, the balance between effectors and regulatory T lymphocytes was tipped towards the detrimental effector immune response, with the two induction agents studied (thymoglobulin and basiliximab). Overall, these results indicate that monitoring these immunological parameters may be very useful for the clinical follow-up of transplant recipients ; these tests may contribute to identify patients who are more likely to develop rejection or, on the contrary, who tolerate well their graft, in order to adapt the immunosuppressive treatment on an individual basis.

CD4(+) T cell count decreases by ethnicity among untreated patients with HIV infection in South Africa and Switzerland.

BACKGROUND: Estimates of the decrease in CD4(+) cell counts in untreated patients with human immunodeficiency virus (HIV) infection are important for patient care and public health. We analyzed CD4(+) cell count decreases in the Cape Town AIDS Cohort and the Swiss HIV Cohort Study. METHODS: We used mixed-effects models and joint models that allowed for the correlation between CD4(+) cell count decreases and survival and stratified analyses by the initial cell count (50-199, 200-349, 350-499, and 500-750 cells/microL). Results are presented as the mean decrease in CD4(+) cell count with 95% confidence intervals (CIs) during the first year after the initial CD4(+) cell count. RESULTS: A total of 784 South African (629 nonwhite) and 2030 Swiss (218 nonwhite) patients with HIV infection contributed 13,388 CD4(+) cell counts. Decreases in CD4(+) cell count were steeper in white patients, patients with higher initial CD4(+) cell counts, and older patients. Decreases ranged from a mean of 38 cells/microL (95% CI, 24-54 cells/microL) in nonwhite patients from the Swiss HIV Cohort Study 15-39 years of age with an initial CD4(+) cell count of 200-349 cells/microL to a mean of 210 cells/microL (95% CI, 143-268 cells/microL) in white patients in the Cape Town AIDS Cohort > or =40 years of age with an initial CD4(+) cell count of 500-750 cells/microL. CONCLUSIONS: Among both patients from Switzerland and patients from South Africa, CD4(+) cell count decreases were greater in white patients with HIV infection than they were in nonwhite patients with HIV infection.

Cystatin C as a marker of early changes of renal function in Fabry nephropathy.

BACKGROUND: A sensitive, feasible and reproducible marker for renal function is necessary to evaluate the clinical efficacy of enzyme replacement therapy (ERT) in Fabry nephropathy. Serum creatinine has some limitations and cystatin C has been proposed, in other nephropathies, as a useful marker of renal function. The use of cystatin C as a marker of glomerular filtration rate (GFR) was investigated in Fabry patients receiving ERT. METHODS: Renal function was evaluated with serum creatinine, serum cystatin C and estimated GFR (through Modification of Diet in Renal Disease [MDRD], Cockcroft-Gault [C&G] and Hoek formulae) in 21 Fabry patients receiving ERT with agalsidase alfa for 3 years and in 13 Fabry patients receiving agalsidase alfa for 4 years. RESULTS: During years of ERT while serum creatinine remained stable, cystatin C values showed a significant, increasing trend right from the first year of ERT. CONCLUSIONS: In Fabry disease, cystatin C is a sensitive and reliable marker of renal function, and it should be taken into account when evaluating GFR trends during ERT.

Visual activity predicts auditory recovery from deafness after adult cochlear implantation.

Modern cochlear implantation technologies allow deaf patients to understand auditory speech; however, the implants deliver only a coarse auditory input and patients must use long-term adaptive processes to achieve coherent percepts. In adults with post-lingual deafness, the high progress of speech recovery is observed during the first year after cochlear implantation, but there is a large range of variability in the level of cochlear implant outcomes and the temporal evolution of recovery. It has been proposed that when profoundly deaf subjects receive a cochlear implant, the visual cross-modal reorganization of the brain is deleterious for auditory speech recovery. We tested this hypothesis in post-lingually deaf adults by analysing whether brain activity shortly after implantation correlated with the level of auditory recovery 6 months later. Based on brain activity induced by a speech-processing task, we found strong positive correlations in areas outside the auditory cortex. The highest positive correlations were found in the occipital cortex involved in visual processing, as well as in the posterior-temporal cortex known for audio-visual integration. The other area, which positively correlated with auditory speech recovery, was localized in the left inferior frontal area known for speech processing. Our results demonstrate that the visual modality's functional level is related to the proficiency level of auditory recovery. Based on the positive correlation of visual activity with auditory speech recovery, we suggest that visual modality may facilitate the perception of the word's auditory counterpart in communicative situations. The link demonstrated between visual activity and auditory speech perception indicates that visuoauditory synergy is crucial for cross-modal plasticity and fostering speech-comprehension recovery in adult cochlear-implanted deaf patients.