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Immunotherapy prolongs survival in only a subset of melanoma patients, highlighting the need to better understand the driver tumor microenvironment. We conducted bioinformatic analyses of 703 transcriptomes to probe the immune landscape of primary cutaneous melanomas in a population-ascertained cohort. We identified and validated 6 immunologically distinct subgroups, with the largest having the lowest immune scores and the poorest survival. This poor-prognosis subgroup exhibited expression profiles consistent with β-catenin–mediated failure to recruit CD141+ DCs. A second subgroup displayed an equally bad prognosis when histopathological factors were adjusted for, while 4 others maintained comparable survival profiles. The 6 subgroups were replicated in The Cancer Genome Atlas (TCGA) melanomas, where β-catenin signaling was also associated with low immune scores predominantly related to hypomethylation. The survival benefit of high immune scores was strongest in patients with double-WT tumors for BRAF and NRAS, less strong in BRAF-V600 mutants, and absent in NRAS (codons 12, 13, 61) mutants. In summary, we report evidence for a β-catenin–mediated immune evasion in 42% of melanoma primaries overall and in 73% of those with the worst outcome. We further report evidence for an interaction between oncogenic mutations and host response to melanoma, suggesting that patient stratification will improve immunotherapeutic outcomes.

This thesis examines the presence of modernist ideas regarding identity, language and narrative in the work of the neglected Sardinian author, Grazia Deledda (1871-1936). It has the overall aim of redefining Deledda’s later work as modernist for she has been disregarded by most critics and is generally classed as a minor, veristic writer. Drawing Deledda out of these restricted interpretations, this thesis demonstrates that Deledda straddles two literary modes, for she matures beyond veristic influences and looks forward to modernist ideas, particularly regarding the complex nature of the self. The thesis approaches Deledda from an entirely new perspective in that it focuses upon the crisis of identity in Deledda’s work, and its construction in the narrative of her novels, and its integral relationship with the theme of language. The theoretical framework of Julia Kristeva, Paul Ricoeur and Adriana Cavarero enables an innovative study of identity as a linguistic and narrative construct in Deledda’s work. I maintain that Deledda’s characters construct, control and understand their identities through their application of language or their command of narrative perspective, voicing their inner selves through linguistic self-expression. This study engages in a close textual analysis of three of Deledda’s key texts. La madre (1920) and Il segreto dell'uomo solitario (1921) illustrate Deledda’s movement away from verismo. Their protagonists suffer a crisis of identity which is bound up in linguistic expression and/or narrative control. Cosima (1937), which is Deledda’s most autobiographical text, displays the author’s close affinity with her writing. Creating a fiction of her own life, Deledda becomes both narrator and protagonist, self and other in the exploration of her own identity, which is integrally connected to the act of writing. The very composition of this text demonstrates the construction of identity in language and narrative which is illustrated within Deledda’s other works.

Antibody (Ab) discovery research has accelerated as monoclonal Ab (mAb)-based biologic strategies have proved efficacious in the treatment of many human diseases, ranging from cancer to autoimmunity. Initial steps in the discovery of therapeutic mAb require epitope characterization and preclinical studies in vitro and in animal models often using limited quantities of Ab. To facilitate this research, our Shared Resource Laboratory (SRL) offers microscale Ab conjugation. Ab submitted for conjugation may or may not be commercially produced, but have not been characterized for use in immunofluorescence applications. Purified mAb and even polyclonal Ab (pAb) can be efficiently conjugated, although the advantages of direct conjugation are more obvious for mAb. To improve consistency of results in microscale (

In this conference presentation, the author, contrary to traditional views, offers a marketing definition that is compatible with continuing education goals. She then points out five reasons why continuing education activities for nurses should be marketed. (EM)

Cape fur seals Arctocephalus pusillus pusillus were harvested to extirpation on the Robberg Peninsula, Plettenberg Bay, on the south-east coast of South Africa, between the 17th and early 20th centuries. Seals returned to Robberg in small numbers during the early 1990s and their numbers subsequently increased. We studied the diet of this increasing population using faecal (scat) sampling to determine: the species composition and size of prey in the diet of Cape fur seals at Robberg; to explore temporal variation in the diet; and to investigate the potential for competition between seals and the fisheries around Plettenberg Bay. Of the 445 scats collected, 90% contained hard prey remains and 15 teleost prey species were represented in the 3 127 otoliths that could be identified. The seals’ most important prey species in terms of numerical abundance, frequency of occurrence and mass in the diet, were anchovy Engraulis encrasicolus, sardine Sardinops sagax, horse mackerel Trachurus capensis, sand tongue-fish Cynoglossus capensis and shallow-water hake Merluccius capensis (in decreasing order of importance for numerical abundance). The proportion of anchovy in the diet increased during the study period (2003–2008), whereas the proportion of sardine decreased. The estimated average annual consumption of sardine by seals was higher than the average annual catch made by purse-seine fisheries in this area, suggesting resource competition between seals and purse-seiners, especially in the light of continuing growth of seal numbers in the area. However, direct competition between seals and linefisheries appeared to be minimal. Scat sampling of Cape fur seals holds potential to serve a useful and cost effective indicator of temporal changes in sardine abundance. Keywords: marine protected area, pinnipeds, sardine, scat analysis, South AfricaAfrican Journal of Marine Science 2012, 34(3): 431–441

A partir de todos los nacimientos ocurridos en el Uruguay entre 2002 y 2003 y las defunciones ocurridas en el primer año de vida, se estima la tasa de mortalidad infantil a través de modelos probit y hazard. Debido a que las muertes se concentran en los primeros días y semanas de vida, el modelo hazard es preferible al probit, encontrándose que la estimación probit sobreestima los efectos de las covariables. Los resultados muestran que las variables más importantes son la edad y la educación de la madre, los cuidados prenatales y los denominados predictores de la mortalidad (bajo peso al nacer, semanas de gestación y APGAR). Based on all the births that occurred in Uruguay between 2002 and 2003 and all the deaths that occurred during the first year of life, the infant mortality rate by way of the probit and hazard models is estimated. Since the deaths concentrate in the first days and weeks of life, the hazard model is preferable to the probit model, since it was found the probit estimation overestimates the effect of the co-variables. The results show that the most important variables are the mother´s age and education level, prenatal care and the referred to as the mortality predictors -low birth weight, gestation weeks and APGAR (Adaptation, Partnership, Growth, Affection and Resolve)-. À partir des statistiques de naissance et de décès dans la première année de vie en Uruguay entre 2002 et 2003, on estime le taux de mortalité infantile à travers des modèles probit et hazard. Étant donné que les morts se concentrent dans les premiers jours et semaines de vie, le modèle hazard est préférable au probit. On trouve que l’estimation probit surestime les effets des co-variables. Les résultats montrent que les variables explicatives les plus importantes sont l’âge et l’éducation de la mère, les soins prénatals et les variables physiologiques traditionnellement associées à la mortalité (un bas poids du nouveau né, le nombre des semaines de gestation et l’APGAR).

A partir de todos los nacimientos ocurridos en el Uruguay entre 2002 y 2003 y las defunciones ocurridas en el primer año de vida, se estima la tasa de mortalidad infantil a través de modelos probit y hazard. Debido a que las muertes se concentran en los primeros días y semanas de vida, el modelo hazard es preferible al probit, encontrándose que la estimación probit sobreestima los efectos de las covariables. Los resultados muestran que las variables más importantes son la edad y la educación de la madre, los cuidados prenatales y los denominados predictores de la mortalidad (bajo peso al nacer, semanas de gestación y APGAR).

This article presents a study of the relationship between self-reported happiness and selfassessed health status at the individual level, using the Religion, Health, and Young Emancipation ISSP survey for Uruguay in 2008. Probit estimates suggest that better selfassessed health status is highly correlated with greater levels of self-reported happiness. In order to control for the observed heterogeneity, models are estimated using matching methods. Results show that individuals who report themselves to be in good health have a probability of being at the highest level of happiness between 18 and 29 percentage points higher than individuals who report worse health., The authors thank the University of North Texas and the University of Pennsylvania for funding this study.

Este estudio investiga el impacto de factores de riesgo en el peso al nacer de los neonatos de la principal maternidad del Uruguay, el Centro Hospitalario Pereira Rossell, hospital público que atiende fundamentalmente población de bajos ingresos. La información proveniente del Sistema Informático Perinatal (CLAP, OPS/OMS) cubre los nacimientos registrados entre 1995 y 2004. Se encuentra que la mayoría de los factores de riesgo incluidos son significativos predictores, tanto del peso al nacer como del bajo peso al nacer. Aquellos que pueden ser influidos por políticas públicas (uso de cuidados prenatales y educación) tienen un efecto significativo en el peso al nacer; sin embargo, también lo tienen los factores de riesgo epidemiológicos. Por tanto, es importante incrementar la utilización adecuada de los controles prenatales y la educación materna, pero también lo es para los hacedores de política considerar caminos que reduzcan la ocurrencia de ciertos factores de riesgo epidemiológicos "evitables", como ser hábito de fumar de la madre, cortos períodos interembarazos y edades extremas de la madre. This study investigates the impact of risk factors on birthweight in the main maternity hospital in Uruguay, Centro Hospitalario Pereira Rossell. The data are provided by the Latin American Center for Perinatology and cover the years 1995 to 2004. The study finds that most of the included risk factors are significant predictors of both birthweight and the probability of a low-birthweight birth. As expected, risk factors that can be influenced by public policy (prenatal care usage, education, and smoking) have significant effects on birthweight outcomes; however, the results indicate that epidemiological risk factors that are less easily affected by public policy (previous low-birthweight births and short pregnancy interval) have similar effects on birthweight outcomes. Thus, although it is important to increase prenatal care usage and maternal educational attainment and to decrease maternal smoking in order to improve birthweight outcomes in Uruguay, it is also important for policymakers to consider ways to reduce the occurrence of epidemiological risk factors.