STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

BACKGROUND: The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. METHODS/DESIGN: STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. DISCUSSION: The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. TRIAL REGISTRATION: STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013. STRATEGIC-1 is registered at EudraCT-No.: 2013-001928-19, 25 April, 2013.

Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [<1.0 mmol/L] for at least 2 h) were identified among 26 patients. During GD, we found a significant increase of CMD lactate (from 4±2.3 to 5.4±2.9 mmol/L), pyruvate (126.9±65.1 to 172.3±74.1 μmol/L), and lactate/pyruvate ratio (LPR; 27±6 to 35±9; all, p<0.005), while brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r=0.56; p<0.0001), while an inverse correlation (r=-0.11; p=0.04) was observed at elevated LPR >25. The correlation between blood and brain glucose also decreased from r=0.62 to r=0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

Interventions présumées des scribes concernant le motif de l'arbre sacré dans le Pentateuque

Abstract: This article deals with several presumed scribal interventions which all concern the sacred tree motif. One finds deliberate changes in the MT, in the Septuagint, in Targum Onkelos and in the Vulgate. The Greek translators of Genesis and Samuel (1-2 Kingdoms) avoided rendering the word אשׁל "tamarisk" by its equivalent μυρίκη, chosing instead the word ἄρουρα "field". Similarly, the Greek translator of Genesis, in the passage of the death of Rebecca's nurse Deborah, passed over the motif of her burial under a grand tree. According to the hypothesis of the present article, all four changes are related to one other; they might be due to the translator's fear to connect the respective texts with traditions and customs concerning the Egyptian god Osiris. On the other side, a scribe of the proto-Massoretic tradition modified the readings mentioning the large tree of Mamre close to Hebron. By changing the noun's number from singular to plural the corrector tried to conceal the existence and importance of the sacred tree in the tradition of Abraham. By contrast, the scribe did not modify texts related to the sacred tree of Shechem. This disparity of treatment may be explained by the fact that, in the view of the Judean scribe, the tree of Shechem would put the Samaritans in a bad light. Finally, the authors of Targum Onkelos and of the Vulgate intervened almost systematically in Pentateuchal texts having the terms אֵלוֹן) אלון or אַלּוֹן ), which always designate a holy tree. The two expressions are rendered by terms referring to plains (Targum Onkelos) or a valley (Vulgate).

Immunogenicity of dimorphic and C-terminal fragments of Plasmodium falciparum MSP2 formulated with different adjuvants in mice.

BACKGROUND: Plasmodium falciparum MSP2 is a blood stage protein that is associated with protection against malaria. It was shown that the MSP2 dimorphic (D) and constant (C) regions were well recognized by immune human antibodies, and were characterized by major conserved epitopes in different endemic areas and age groups. These Abs recognized merozoite-derived proteins in WB and IFA. Here, the goal was to determine in mice the immunogenicity of the two allelic MSP2 D and C domains formulated with different adjuvants, for their possible use in future clinical studies. METHOD: Female A/J, C3H, and ICR mice were immunized subcutaneously 3 times at 3-week interval with a mixture of allelic and conserved MSP2 long synthetic peptides formulated with different adjuvants. One week after the third injection, sera from each group were obtained and stored at -20°C for subsequent testing. RESULTS: Both domains of the two MSP2 families are immunogenic and the fine specificity and intensity of the Ab responses are dependent on mouse strains and adjuvants. The major epitopes were restricted to the 20-mer peptide sequences comprising the last 8aa of D and first 12aa of C of the two allelic families and the first 20aa of the C region, this for most strains and adjuvants. Strong immune responses were associated with GLA-SE adjuvant and its combination with other TLR agonists (CpG or GDQ) compared to alhydrogel and Montanide. Further, the elicited Abs were also capable of recognizing Plasmodium-derived MSP2 and inhibiting parasite growth in ADCI. CONCLUSION: The data provide a valuable opportunity to evaluate in mice different adjuvant and antigen formulations of a candidate vaccine containing both MSP2 D and C fragments. The formulations with GLA-SE seem to be a promising option to be compared with the alhydrogel one in human clinical trials.

Pensamiento geográfico versus teoría de la comunicación. Hacia un modelo de análisis comunicativo del paisaje

The study of the communicative implications related to landscapes opens a wide range of possibilities concerning the treatment of the communication and landscape relationship. Issues such as the effects of the landscape on the processes of human communication (intrapersonal and interpersonal communication), the follow-up of the communicative processes by means of which the landscape becomes an object of trade (mass communication), the construction of individual and collective imaginaries arising from the citizenship and landscape exchange and, recently, the construction of territorial identities through the production of a brand image of a city or country (i. e., tourist promotion, city marketing and branding). All of them have important implications in the contemporary societies. For that reason, it appears almost essential to progress towards a communicative landscape model, a target which becomes possible if we interrelate geography and communication studies, two fields apparently unrelated one another concerning their origins and practice, although they are very close if we look at the recent evolution of their paradigms and the approach to certain concepts, such as space and landscape.

Aportació de les traduccions rosselloneses del segle XIX a la construcció del sistema lingüisticoliterari català

Qui vulgui parlar de les traduccions catalanes impreses al Rosselló ha de fer un apunt inevitable i esmentar els orígens de la impremta rossellonesa. El primer llibre imprès a Perpinyà, l’any 1502, és el Vocabulari molt profitos per aprendre lo Catalan Alamany y lo Alamany Catalan. És un extens glossari bilingüe per a la traducció de cent quaranta- dues pàgines. El segon llibre imprès a Perpinyà, l’any 1503, és una traducció del llatí feta per Narcís Solà. És un llibre renaixentista de medicina de Pere de Argilata: Aci comensa la cirurgia del reverende meritissim doctor en arts e en medicina Le reverent mestre Pere de Argilata de la ciutat de Bolonia d’una extensió de tres-centes vuit pàgines. Així doncs, la impremta al Rosselló començà amb dues traduccions. En el segle immediatament anterior al del nostre estudi, el segle xviii, podem comptar al Rosselló fins a vint-i-nou llibres impresos en català1 dels quals set són traduccions: quatre del francès, dues del castellà i una del llatí. Tant les set traduccions com els altres vint-idos llibres són de temàtica religiosa. Llibres de pietat, exercicis espirituals i un catecisme. Destaca, en el grup de les set traduccions, una tragèdia clàssica de tema bíblic Esther: tragedia santa de Jean Racine.

De senio hominis

Invocatio: Numine Maximo Favente!.

De interpretatione juris naturalis

Invocatio: D.A.F.

Avaliação da Dispersão primária e secundária do Tomato severe rugose virus para genótipos de Capsicum spp. por Bemisia tabaci MEAM1

A mosca branca Bemisia tabaci (Hemiptera: Aleyrodidae) é considerada uma das pragas agrícolas mais ameaçadoras em todo o mundo, pelo seu efeito direto na sucção de seiva das plantas e principalmente pelo seu efeito indireto de transmitir vírus, em especial os begomovírus. No Brasil, a espécie de begomovírus predominante em solanáceas é o Tomato severe rugose vírus - ToSRV. Uma possibilidade de manejo da doença é a utilização de cultivares resistentes ou tolerantes tanto ao vírus, como ao inseto vetor. Foram avaliados neste trabalho a dispersão primária e secundária do ToSRV por Bemisia tabaci, espécie MEAM1, também conhecida como biótipo B, em cultivares tolerantes ao ToSV Capsicum baccatum (IAC-1357) C. annuum (IAC-1566) e C. frutescens (IAC-1544). O genótipo (IAC-1544) apresentou menor número de plantas infectadas pelo ToSRV no ensaio de dispersão primária e nenhuma eficiência na transmissão do isolado na dispersão secundária. Estes resultados colaboram para o melhoramento de pimentão e pimentas visando a resistência ao ToSRV e seu inseto vetor.

L'Univers

1871/09/28 (Numéro 1566).

L'Univers

1871/07/26 (Numéro 1503).

Dictionnaire francois latin contenant les motz et manières de parler francois, tournez en latin ([Reprod.])

[Dictionnaire français-latin (français moyen-latin). 1539 fac-sim.]

Armon lähteillä : editio englantilaisista ja walesilaisista penitentiariaattiasiakirjoista

Kirjallisuusarvostelu

Cosmographia universalis ab Orontio olim descripta

Julkaisussa: Geografia tavole moderne di geografia de la maggior parte del mondo di diversi autori

Opera di M. Giacomo Gastaldi Piamontese cosmografo in Venetia disegno, particolare de regni e regioni, che son da Venetia, a Constantinopoli, et da Constantinopoli, a Vienna, d'Austria et da Vienna ..

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan