The Traveler, August, 2002

Newsletter for Economic Development

Urban health: l'irrémédiable urbanisation de la vie et de la médecine [Urban health: the irremediable urbanization of life and medicine].

Since 2007, the number of people living in cities exceeds that of rural areas. Thus, cities and their organizations have a major influence on all spheres of human life, especially health. This influence may generate inequality, suffering and disease, but also represent an opportunity for health and well-being. This paper introduces the concept of urban health, particularly in terms of primary care medicine and presents solutions that encompass a wide field (politics, urban planning, social inequality, education). Improving urban health requires collaboration of medical with non-medical actors, in order to become of development (re-) urban structure and promotes the health of all.

Use of an in-house approach to study the three-dimensional structures of various outer membrane proteins: structure of the alcaligin outer membrane transporter FauA from Bordetella pertussis.

Bordetella pertussis is the bacterial agent of whooping cough in humans. Under iron-limiting conditions, it produces the siderophore alcaligin. Released to the extracellular environment, alcaligin chelates iron, which is then taken up as a ferric alcaligin complex via the FauA outer membrane transporter. FauA belongs to a family of TonB-dependent outer membrane transporters that function using energy derived from the proton motive force. Using an in-house protocol for membrane-protein expression, purification and crystallization, FauA was crystallized in its apo form together with three other TonB-dependent transporters from different organisms. Here, the protocol used to study FauA is described and its three-dimensional structure determined at 2.3 A resolution is discussed.

Contribution of major cardiovascular risk factors to familial premature coronary artery disease: the GENECARD project.

OBJECTIVES: This study was designed to assess the prevalence of major cardiovascular risk factors in familial premature coronary artery disease (P-CAD), affecting two or more siblings within one sibship. BACKGROUND: Premature CAD has a genetic component. It remains to be established whether familial P-CAD is due to genes acting independently from major cardiovascular risk factors. METHODS: We recruited 213 P-CAD survivors from 103 sibships diagnosed before age <or=50 (men) or <or=55 (women) years old. Hypertension, hypercholesterolemia, obesity, and smoking were documented at the time of the event in 163 patients (145 men and 18 women). Each patient was compared with two individuals of the same age and gender, diagnosed with sporadic (nonfamilial) P-CAD, and three individuals randomly sampled from the general population. RESULTS: Compared with the general population, patients with sporadic P-CAD had a higher prevalence of hypertension (29% vs. 14%, p < 0.001), hypercholesterolemia (54% vs. 33%, p < 0.001), obesity (20% vs. 13%, p < 0.01), and smoking (76% vs. 39%, p < 0.001). These risk factors were equally or even more prevalent in patients with familial P-CAD (43% [p < 0.05 vs. sporadic P-CAD], 58% [p = 0.07], 21% and 72%, respectively). Overall, only 7 (4%) of 163 of patients with familial P-CAD and 22 (7%) of 326 of patients with sporadic P-CAD had none of these conditions, as compared with 167 (34%) of 489 patients in the general population. CONCLUSIONS: Classic, remediable risk factors are highly prevalent in patients with familial P-CAD. Accordingly, a major contribution of genes acting in the absence of these risk factors is unlikely.

Portugais 48

Contient : 1 Recueil de généalogies portugaises ; 2 Recueil de généalogies extraites "de hum livro de Nunalvares Pereira" ; 3 Recueil de généalogies : "Estos linages que se siguen se copiaron de un libro de Alonsso Lopez de Haro de los linages de Portugal, y, por lo que dize en el de los Pimenteles, parece se le dio Nunalbarez Pereyra." ; 4 "Desçendencia dos Teives feita por D. Belchor de Teive." ; 5 Notes sur divers membres de la famille de Mello ou Merlo ; 6 "Familia y quadrilla de Blasco Ximeno." Cette généalogie se termine par une notice sur D. Gomez d'Avila y Toledo, deuxième marquis de Velada ; 7 "Linhagem dos de Castelbranco, recopilada por Dom Manoel de Castelbranco, conde de Villanova." ; 8 Notes généalogiques sur les familles Pinheiro, Manoel et Tserclaes ; 9 "Memoria dos titulos que os reis de Portugal criarão de novo neste reyno," de João Ier à Philippe III ; 10 "Los grandes y titulos de Castilla." ; 11 "Visoreys e governadores da India." ; 12 Notes généalogiques sur les Souza et les Maldonado ; 13 "Adiantados que ouve em Portugal." ; 14 "Epitaphios que estão no mosteiro de S. Antonio da Castanheyra." ; 15-34 Documents relatifs à la prise de la ville de Salvador (Bahia, Brésil) par les hollandais (1624) et à la reprise par l'armée hispano-portugaise (1625) ; 15 "Lista dos navios, capitaes d'elles e soldados, fidalgos e nobres que se embarcarão e partirão ao soccorro da Bahia, a 21 de novembro de 1624, sendo capitão geral d'esta armada don Manoel de Meneses." ; 16 "Relaçaõ do dinheiro e cousas reduzidas a elle com que este reyno servio a Sua Magd na ocasiaõ do apresto da armada para o socorro da Bahia no Brasil, que vae ao todo noventa e tres contos coatrocentos e hum mil." 1624 ; 17 "Relaçaõ da armada que partio de Lisbóa em socorro da Bahia e do susseço que teve." ; 18 "Carta para hum fidalgo recidente na corte de Madrid, em que brevemente se relata o corpo principal de toda a armada, que d'este porto de Lixboa salio para a empreza da Bahya, aos 23 de novembro de 1624." Lisbonne, 12 décembre 1624 ; 19 "Relaçaõ das armadas de Sua Magde do dia em que chegaraõ a Bahia e do que se tem feito na expugnaçaõ do enemigo, desde 29 de março que foi vespera de Pascoa, em que deraõ fundo na dita Baia as armadas, ate 22 abril, em que se mandou a Pernambuco o papel de que se tirou esta rellaçaõ, a qual mandaraõ os governadores de Portugal a Sua Magde." 1625 ; 20 "Relaçion de Lorenço Perez Carballo de lo que pasa en la Baya, de quinçe de abril de 1625." ; 21 "Copia da carta que dom Manoel de Menezes, capitaõ mor da armada da esquadra de Portugal, escreveo a S. Mgde, da Bahia, dando conta do que succedeo nella, desde 29 de março te 12 de mayo de 1625." ; 22 "Relaçaõ de que o capitaõ don Manoel de Meneses faz mençaõ na sua carta atraz." 1625 ; 23 "Discurso breve del suçeso que han tenido las armas de su Magd en la jornada del Brasil, desde que salieron de España asta la rrestauraçion de la çiudad de San Salvador, que tomaron los Olandeses en diez de mayo del año pasado de mill y seisçientos y veinte y quatro... Fecha en diez de mayo de mill y seisçientos y veinte y cinco." ; 24 "Copia de las cartas y respuestas que ubo de parte de los Olandeses y Don Fadrique de Toledo Ossorio, desde 28 de abril [1625] hasta 30 que se rindio la plaza" de San Salvador ; 25 "Capitulos conspirados por el sor Coronel y los del Conssejo en la Baya para ofreçer a su Exa Don Fadrique de Toledo, general por su Mgd d'España." 29 et 30 avril 1625 ; 26" Relacion del viaje y sucesso de la Armada que por mandado de su Magestad partio al Brasil, a echar de alli los enemigos que lo ocupavam. Francisco de Avendaño y Vilela. En Sevilla por Francisco de Lyra, año de 1625." ; 27 "Relaçion de la jornada que ba haziendo la armada real a las partes del Brasil, que salio de la baya de Cadiz, martes á catorze de henero de seiscientos y veinte y cinco." ; 28 État-major des tercios de D. Juan de Orellana et D. Pedro Osorio et du tercio de Naples du marquis de Torrecusso, embarqués à Cadix pour le Brésil, le 14 janvier 1625 ; 29 "Brevis, succinta ac vera narratio expeditionis illius, quam quidam mercatores sub auspiciis et autoritate illustrium D. D. ordinum Holandiae, Zelandiae, etc. suseperunt in Brasilium, anno 1623." ; 30 Relation de combats entre Portugais et Hollandais sur les côtes du Brésil ; 31 Notes généalogiques sur les familles Costa, Correa de Moura et Moreno, communiquées au compilateur du recueil par D. Luis Lobo et D. Antonio Correa Barem ; 32 "Relaçaõ do que o capitaõ Francisco de Padilha fes en quanto andou nos asaltos ate a vinda da armada." 1624 ; 33 Relation de l'attaque de Sam Bento au Brésil, en 1625 ; 34 Relation de l'expédition des flottes espagnole et portugaise au Brésil et de la prise de San Salvador. 1625

Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.

Background Following the discovery that mutant KRAS is associated with resistance to anti-epidermal growth factor receptor (EGFR) antibodies, the tumours of patients with metastatic colorectal cancer are now profiled for seven KRAS mutations before receiving cetuximab or panitumumab. However, most patients with KRAS wild-type tumours still do not respond. We studied the effect of other downstream mutations on the efficacy of cetuximab in, to our knowledge, the largest cohort to date of patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab plus chemotherapy in the pre-KRAS selection era. Methods 1022 tumour DNA samples (73 from fresh-frozen and 949 from formalin-fixed, paraffin-embedded tissue) from patients treated with cetuximab between 2001 and 2008 were gathered from 11 centres in seven European countries. 773 primary tumour samples had sufficient quality DNA and were included in mutation frequency analyses; mass spectrometry genotyping of tumour samples for KRAS, BRAF, NRAS, and PIK3CA was done centrally. We analysed objective response, progression-free survival (PFS), and overall survival in molecularly defined subgroups of the 649 chemotherapy-refractory patients treated with cetuximab plus chemotherapy. Findings 40.0% (299/747) of the tumours harboured a KRAS mutation, 14.5% (108/743) harboured a PIK3CA mutation (of which 68.5% [74/108] were located in exon 9 and 20.4% [22/108] in exon 20), 4.7% (36/761) harboured a BRAF mutation, and 2.6% (17/644) harboured an NRAS mutation. KRAS mutants did not derive benefit compared with wild types, with a response rate of 6.7% (17/253) versus 35.8% (126/352; odds ratio [OR] 0.13, 95% CI 0.07-0.22; p<0.0001), a median PFS of 12. weeks versus 24 weeks (hazard ratio [HR] 1 98, 1.66-2.36; p<0.0001), and a median overall survival of 32 weeks versus 50 weeks (1.75, 1.47-2.09; p<0.0001). In KRAS wild types, carriers of BRAF and NRAS mutations had a significantly lower response rate than did BRAF and NRAS wild types, with a response rate of 8.3% (2/24) in carriers of BRAF mutations versus 38.0% in BRAF wild types (124/326; OR 0.15, 95% CI 0.02-0.51; p=0.0012); and 7.7% (1/13) in carriers of NRAS mutations versus 38.1% in NRAS wild types (110/289; OR 0.14, 0.007-0.70; p=0.013). PIK3CA exon 9 mutations had no effect, whereas exon 20 mutations were associated with a worse outcome compared with wild types, with a response rate of 0.0% (0/9) versus 36.8% (121/329; OR 0.00,0.00-0.89; p=0.029), a median PFS of 11.5 weeks versus 24 weeks (HR 2.52, 1.33-4.78; p=0.013), and a median overall survival of 34 weeks versus 51 weeks (3.29, 1.60-6.74; p=0.0057). Multivariate analysis and conditional inference trees confirmed that, if KRAS is not mutated, assessing BRAF, NRAS, and PIK3CA exon 20 mutations (in that order) gives additional information about outcome. Objective response rates in our series were 24.4% in the unselected population, 36.3% in the KRAS wild-type selected population, and 41.2% in the KRAS, BRAF, NRAS, and PIK3CA exon 20 wild-type population. Interpretation While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA,exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.

Variability of radioiodine measurements in the thyroid.

Monte Carlo simulations were carried out to study the response of a thyroid monitor for measuring intake activities of (125)I and (131)I. The aim of the study was 3-fold: to cross-validate the Monte Carlo simulation programs, to study the response of the detector using different phantoms and to study the effects of anatomical variations. Simulations were performed using the Swiss reference phantom and several voxelised phantoms. Determining the position of the thyroid is crucial for an accurate determination of radiological risks. The detector response using the Swiss reference phantom was in fairly good agreement with the response obtained using adult voxelised phantoms for (131)I, but should be revised for a better calibration for (125)I and for any measurements taken on paediatric patients.

Management of Floodpain Forests, June 1987

A river or stream and its floodplain exist in a state of dynamic equilibrium. This four page report explains the management of floodplain forests.

Helsinki 15/7 1943

Kirje 15.7.1943

Cartografías migratorias en África Occidental

En la actualidad nos encontramos ante una reorganización de los grados de ciudadanía en base a la especialización migratoria en función del origen y cultura de adscripción. En tiempos de reestructuración de los mercados financieros y del trabajo, las antiguas y nuevas metrópolis apoyan políticas que pretenden delimitar la movilidad y los espacios transnacionales de determinadas diásporas. Es el caso del apoyo europeo a la conscripción de la libertad de circulación tradicional de la CEDEAO. Resistencia y relaciones postcoloniales se ponen de manifiesto entre Cabo Verde y Guinea Bissau espacio geopolítico de singulares características. Una cartografía implica revisar el contexto territorial, las experiencias pasadas y los discursos de los distintos actores y de pensadores como Amilcar Cabral que pretendió que más allá de la liberación el desarrollo fuera participado por sus protagonistas.

Cooperative games in strategic form

In this paper we view bargaining and cooperation as an interaction superimposed on a strategic form game. A multistage bargaining procedure for N players, the proposer commitment procedure, is presented. It is inspired by Nash s two-player variable-threat model; a key feature is the commitment to threats. We establish links to classical cooperative game theory solutions, such as the Shapley value in the transferable utility case. However, we show that even in standard pure exchange economies the traditional coalitional function may not be adequate when utilities are not transferable.