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Heart disease is the leading cause of death globally, and delivery of therapeutic cargo (e.g., particles loaded with proteins, drugs, cells, or genes) through direct injection into the myocardium is a promising clinical intervention. However, retention of deliverables to the contracting myocardium is low, with as much as 60 – 90% of payload being lost within 24 hours. Commercially-available injectable hydrogels, including Matrigel, have been hypothesized to increase payload retention, but have not yielded significant improvements in quantified analyses. Here, we assess a recombinant hydrogel composed of chemically modified hyaluronan and elastin-like protein (HELP) as an alternative injectable carrier to increase cargo retention. HELP is crosslinked using dynamic covalent bonds, and tuning the hyaluronan chemistry significantly alters hydrogel mechanical properties including stiffness, stress-relaxation rate, and ease of injectability through a needle or catheter. These materials can be injected even after complete crosslinking, extending the time window for surgical delivery. We show that HELP gels significantly improve in vivo retention of microsphere cargo compared to Matrigel, both 1 day and 7 days post-injection directly into the rat myocardium. These data suggest that HELP gels may assist with the clinical translation of therapeutic cargo designed for delivery into the contracting myocardium by preventing acute cargo loss.

Intrinsically disordered proteins and regions (IDPs and IDRs) and their importance in biology are becoming increasingly recognized in biology, biochemistry, molecular biology and chemistry textbooks, as well as in current protein science and structural biology curricula. We argue that the sequence → dynamic conformational ensemble → function principle is of equal importance as the classical sequence → structure → function paradigm. To highlight this point, we describe the IDPs and/or IDRs behind the discoveries associated with 17 Nobel Prizes, 11 in Physiology or Medicine and 6 in Chemistry. The Nobel Laureates themselves did not always mention that the proteins underlying the phenomena investigated in their award-winning studies are in fact IDPs or contain IDRs. In several cases, IDP- or IDR-based molecular functions have been elucidated, while in other instances, it is recognized that the respective protein(s) contain IDRs, but the specific IDR-based molecular functions have yet to be determined. To highlight the importance of IDPs and IDRs as general principle in biology, we present here illustrative examples of IDPs/IDRs in Nobel Prize-winning mechanisms and processes.

Heart disease is the leading cause of death globally, and delivery of therapeutic cargo (e.g. cells, proteins, drugs) through direct injection into the myocardium is a promising clinical intervention. However, retention of deliverables to the contracting myocardium is low, with as much as 60 - 90% of payload being lost within 24 hours. Commercially-available injectable hydrogels, including Matrigel, have been hypothesized to increase payload retention, but have not yielded significant improvements in quantified analyses. Here, we assess a recombinant hydrogel composed of chemically modified hyaluronan and elastin-like protein (HELP) as an alternative injectable carrier to increase cargo retention. HELP is crosslinked using dynamic covalent bonds, and tuning the hyaluronan chemistry significantly alters hydrogel mechanical properties including stiffness, stress-relaxation rate, and ease of injectability through a needle or catheter. These materials can be injected even after complete crosslinking, extending the time window for surgical delivery. We show that HELP gels significantly improve in vivo retention of microsphere cargo compared to Matrigel, both 1 day and 7 days post-injection directly into the rat myocardium. These data suggest that HELP gels may assist with the clinical translation of therapeutic cargo designed for delivery into the contracting myocardium by preventing acute cargo loss.

Resumen: La expansión urbana ha ampliado las distancias y tiempos de viaje de las personas que viven y trabajan en las ciudades. En el Área Metropolitana de Santiago de Chile sus habitantes menos favorecidos enfrentan profundos desafíos, pues tanto sus ingresos como los territorios donde residen revelan una menguada disponibilidad de capitales de movilidad. La presente investigación busca calcular y entender los distintos costos de la movilidad expresados en tiempo y en dinero, a partir de los viajes al trabajo como expresión de las desigualdades urbanas existentes en la ciudad. Se utilizan para esto las Encuestas de Caracterización Socio Económica (CASEN) del Ministerio de Desarrollo Social de 2015 y 2017, que incorporan preguntas sobre la movilidad de las personas. Desde un enfoque cuantitativo, se definen los costos monetarios mensuales de la movilidad de los hogares determinando su porcentaje en el ingreso monetario del hogar y se realiza un análisis complementario considerando distintas variables socioeconómicas. Los resultados evidencian profundas desigualdades debidas al mayor peso del costo del transporte público en los ingresos de los más vulnerables, hecho que se condice con mayores tiempos de viaje debido a la lejanía entre su residencia y los centros laborales, mayor desempleo y menor motorización privada.

International audience; In this work we formulate a Stackelberg Security Game that coordinates resources in a border patrol problem. In this security domain, resources from different precincts have to be paired to conduct patrols in the border due to logistic constraints. Given this structure, models that enumerate the pure defender strategies scale poorly. We describe the set of mixed strategies using a polynomial number of variables but exponentially many constraints that come from the matching polytope. We then include this description in a mixed integer formulation to compute the Strong Stackelberg Equilibrium efficiently with a branch and cut scheme. Since the optimal patrol solution is a probability distribution over the set of exponential size, we also introduce an efficient sampling method that can be used to deploy the security resources every shift. Our computational results evaluate the efficiency of the branch and cut scheme developed and the accuracy of the sampling method.

Self-healing materials represent a paradigm shift from traditional materials development, enabling intrinsic repair of functionality (such as strength) after a catastrophic failure as opposed to part replacement. Several healing mechanisms have been demonstrated in polymeric and ceramic materials, but few in metallic systems. This study demonstrates a novel liquid-assisted self-healing metal-matrix composite (MMC) designed to be capable of over 90% strength recovery after a healing cycle. The aluminum (Al)-based matrix is reinforced with continuous nickel-titanium (NiTi) shape-memory alloy (SMA) reinforcements. Using a tailored heat treatment for healing, a paired effect of crack closure from the SMA reinforcement and partial liquefaction of the matrix occurs. These effects result in a compressive force across the crack surface, and, coupled with increased diffusion rates from the liquefied matrix, produces consolidation and healing in the composite structure. This work provides experimental and computational evidence for the healing mechanism under both tensile and fatigue conditions.

Upper Cretaceous intrusives of limited extent crop out in the Coastal Cordillera near of Valdivia (39°48' S), 100 km west of the main topographic divide of the Andean Cordillera. Given that plutonic rocks of the same age crop out at the same latitudes in the high Andes the coastal intrusives emplaced in a forearc position in the upper plate of a subduction setting. They correspond to hypabyssal intrusives displaying mainly porphyritic texture and lithological variations with microtonalites (minor), porphyritic microgranodiorites (main) and microgranites. They intrude the Upper Paleozoic-Triassic accretionary complex of the Bahia Mansa Metamorphic Complex. These intrusives, that comprise the Chaihuín Pluton and minor stocks of porphyritic felsic rocks, have calc-alkaline affinities with metaluminous and peraluminous character. They are geochemically similar to the contemporaneous main arc-related plutonic rocks of the Gualletué Plutonic Group. The microgranitoids and dacitic rocks from Los Boldos, the low and Loncoche are peculiar because they show an apparently adakitic affinity in Sr/Y and LaN/YbN discriminant diagrams; nevertheless Sr contents of these rocks (<

In the past 10 years, the concept of public space has gradually become a new key topic in Chile’s urban planning debate. Most often linked to sustainable urban growth and sustainable mobility, the concept arises in a context of legal changes aiming to reinforce the street as a public space dedicated to all type of mobilities, including active modes of transport (walking and cycling). These recent legal transformations represent an important shift in Chile’s urban planning, establishing guidelines for the future in order to encourage sustainable mobility and increase public space quality and access in Chile’s cities. This integrated approach to urban development represents a clear tendency to promote a more cohesive society in a context of increasing urban complexity and environmental challenges. It recognizes spatial, socio-economic and environmental issues and aims to articulate urban planning with mobility by seeking a balanced distribution of urban functions in Chilean cities. Although at first glance this new approach seems positive, it is important to analyse these changes through the lens of Chile’s urban production, especially in the case of intermediate Chilean cities that, due to their scale, still have the possibility to redirect their development towards a more sustainable growth. We propose a critical analysis of urban public space production in intermediate Chilean cities. By defining streets as public spaces and enabling specific social practices in line with specific urban contexts, we are able to define streets as a social space dedicated to mobilities. From this position, under what type of conditions are these public spaces planned and designed? What social consequences or conflicts emerge through their implementation? These processes will be illustrated through examples of public space projects and policies developed in intermediate Chilean cities these past few years.

Science fiction had anticipated the prediction of future occurrence of crimes. In fact, that prediction is actually possible. It can be done with some imprecision and by computer algorithms using available data from various sources. The prediction involves approximate time and risk maps of occurrence of certain type of felonies such as home burglaries, armed robberies and violent thefts. The police can then use this information for increasing their patrolling accordingly and thereby reducing the crime occurrence rate. We present a crime prediction solution developed for Chilean large cities. Its novel approach includes three independent software modules which make predictions based on different algorithms. The final prediction is the cooperative integration of the individual ones. The developed system has been tested on historical data and its performance has been considered acceptable for police field use. An interesting result is that the performance of each individual module is inferior to the joint performance, validating a hypothesis that different algorithms may exploit different features of the available data.

International audience; The Upper Jurassic volcanic rocks of the Pre-Cordillera and High Andes of northern Chile (26 - 31°S) represent a back-arc magmatic chain formed during an earlier stage of Andean subduction. After the Callovian, the back-arc basin gradually changed from marine to continental conditions and was characterized by basaltic to rhyolitic rocks erupted along two belts, parallel to the coeval arc. The western belt comprises the Picudo and Algarrobal formations, whereas the eastern belt comprises the Lagunillas Formation and the Quebrada Vicuñita Beds. New major and trace elements data, along with whole rock Sr, Nd and Pb isotopes are presented for these volcanic belts and compared to the geochemical features of the Jurassic and Early Cretaceous arc magmatism. Ar-Ar and U-Pb ages constrain the back arc volcanism to have evolved between 163.9 ± 1.4 and 148.9 ± 1.2 Ma.Rocks belonging to the western belt have steep multi-element patterns and low concentrations of HREE, suggesting the presence of garnet in the source, and a more radiogenic isotopic composition than the arc magmatism. Parental magmas of these back-arc lavas would have been generated through melting of a depleted mantle, although less depleted than the sub-arc mantle, and interacted with minor amounts of Paleozoic crust. The geochemical composition of the rocks belonging to the eastern belt is more heterogeneous and suggests involvement of different magmatic sources, including depleted mantle as well as an OIB-type mantle within the wedge. In spite the fact that the Jurassic Andean arc was built over a continental plate, the architecture of the volcanic chains and geochemical variations observed among the arc and back-arc rocks in northern Chile resemble those in modern island arcs, and thus support the hypothesis that early Andean subduction developed under extensional tectonic conditions.

During the last forty years, Santiago has experienced a series of drastic changes in public transport policies. These changes have ranged widely, from total deregulation to processes that concentrated the management of public transport within the hands of the public sector. From traditional forms of regulations and policies within a framework that is common throughout Latin America, the system then migrated to complete deregulation. Later, it made a return to more traditional regulations, although tendering for concessions was introduced as an innovation. Finally, after a new intervention in 2007, a highly planned system was introduced with a strongly centralized organization of authority. These four major changes, over four decades, leads to the conclusion that Santiago has become a true laboratory for public transport policies and management. However, and regardless of these changes, certain elements have remained unaltered, such as the almost complete dominance of private ownership in the operation of the system (except for the minor public company, which ended during the 1970's), the absence of subsidies for operations (except in the last period) and with authority lying with the national government as opposed to local government. This article reviews the practices of these forty years, analyzing the components of their policies, results and evaluations, as well as the foundations on which these changes are built.

We present a decision support system to help plan preventive border patrols. The system represents the interaction between defenders and intruders as a Stackelberg security game (SSG) where the defender pools local resources to conduct joint preventive border patrols. We introduce a new SSG that constructs defender strategies that pair adjacent precincts to pool resources that are used to patrol a location within one of the two precincts. We introduce an efficient formulation of this problem and an efficient sampling method to construct an implementable defender strategy.

The Pan American Health Organization (PAHO) has conducted a study of Streptococcus pneumoniae in six Latin-American countries: Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay. Sterile site isolates from children aged ≤5 years showing clinical symptoms of pneumonia (as defined by the clinical criteria of WHO), meningitis, sepsis or bacteremia (without infectious foci), arthritis, and peritonitis were the source of most of the invasive pneumococcal isolates collected between the end of 1993 and 1996 in the six participating countries. Partial characterization of these isolates (antibiotic resistance and serotyping) have already been described (Microbiol Drug Resistance 3:(2):131–163, 1997). In the next phase of the study, 326 S. pneumoniae isolates with reduced penicillin susceptibility were transferred to the Laboratory of Microbiology at The Rockefeller University for molecular characterization, and a summary and overview of the findings is described in this article. Some of the most inte...

Lascar Volcano (Atacama, Chile) erupted on 18–20 April 1993. Several sub-Plinian explosions occurred, and some were mushroom-shaped. The highest column rose up to 23 km. Ash clouds crossed South America eastwards. Dacite pumice falls made of blocks and ashes were deposited on the flanks of the volcano as a result of collapsed columns. The pumice contains phenocrysts of plagioclase, enstatite, augite, biotite, magnetite and ilmenite and small crystals of apatite. The 1992 previous andesite dome inside the crater was destroyed. Banded blocks resulting from mingling of the dacitic pumice and andesite from the dome are found in the pumice flow. Both the lava dome and the pumice are representative of the Lascar high-K magma unit. Dacitic pumice is a product of crystal fractionation of the andesitic magma.

International audience; The role of daily mobility as a socio-spatial inequalities factor is a key issue in Latin America and is partly attributable to urbanisation patterns on this continent: a rather advanced urban transition, low density and wide spread millionaire metropolises, deep social inequalities, high socio-residential segregation, and an inequitable work distribution within the city. The purpose of this paper is to investigate the relation between daily trips to work and socio-spatial inequalities in three contrasted metropolises (Bogotá, Santiago, São Paulo). We demonstrate that beyond the social hierarchy effect, the territorial effect is determining on people’s daily mobility conditions.; La question du rôle des mobilités quotidiennes comme facteur d’inégalités socio-spatiales se pose avec une grande acuité en Amérique latine, du fait des caractéristiques de l’urbanisation sur ce continent : une transition urbaine bien avancée, des métropoles « millionnaires » très étalées et peu denses, marquées par de profondes inégalités sociales, une très forte ségrégation socio-résidentielle, ainsi qu’une inéquitable répartition des emplois dans la ville. L’objectif est d’explorer ici le lien entre les déplacements domicile-travail et les inégalités socio-spatiales dans trois métropoles contrastées (Bogotá, Santiago, São Paulo). Nous montrons qu’au-delà du simple effet de la hiérarchie sociale, l’effet territorial est déterminant sur les conditions de mobilité quotidienne des citadins.

To determine the factors responsible for the dramatic fall in cholesterol levels after coronary artery bypass surgery (CABG), the authors reviewed, in a retrospective study, the cholesterol levels of 36 patients who underwent CABG surgery during 1987 and compared their levels with those of a control group of 30 patients who underwent cholecystectomies during the same time. In a prospective study, the authors measured the lipids and the hematocrit levels of 15 patients undergoing CABG surgery before the initiation of cardiopulmonary bypass, after 5 minutes of extracorporeal circulation (ECC), and at the end of ECC. In the CABG group, the plasma cholesterol level fell from 211 +/- 63 mg/dl (mean +/- SE) to 70 +/- 48 mg/dl (p less than 0.01), a 77% decrease within 24 hours of surgery. In the cholecystectomy group, the plasma cholesterol fell from 192.3 +/- 8.9 mg/dl to 158 +/- 76 mg/dl (p less than 0.01), an 18% decrease within 24 hours of surgery. To estimate the contribution of hemodilution or blood loss to the fall in cholesterol, changes in hematocrit were recorded. In the CABG group, hematocrit fell from 39.5 +/- 0.7% to 23.5 +/- 0.7% 24 hours after surgery (41% decrease) (p less than 0.01), whereas in the cholecystectomy group hematocrit fell from 39.4 +/- 0.8% to 37.1 +/- 0.9% on the first postoperative day (6% decrease). There was a positive correlation between the fall in cholesterol and the fall in hematocrit in the CABG group (correlation coefficient 0.472), suggesting that hemodilution was a major factor in the decrease in cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

The N–S oriented Coastal Cordillera of South Central Chile shows marked lithological contrasts along strike at ∼38°S. Here, the sinistral NW–SE-striking Lanalhue Fault Zone ( nomen novum ) juxtaposes Permo-Carboniferous magmatic arc granitoids and associated, frontally accreted metasediments (Eastern Series) in the northeast with a Late Carboniferous to Triassic basal-accretionary forearc wedge complex (Western Series) in the southwest. The fault is interpreted as an initially ductile deformation zone with divergent character, located in the eastern flank of the basally growing, upwarping, and exhuming Western Series. It was later transformed and reactivated as a semiductile to brittle sinistral transform fault. Rb–Sr data and fluid inclusion studies of late-stage fault-related mineralizations revealed Early Permian ages between 280 and 270 Ma for fault activity, with subsequent minor erosion. Regionally, crystallization of arc intrusives and related metamorphism occurred between ∼306 and ∼286 Ma, preceded by early increments of convergence-related deformation. Basal Western Series accretion started at >290 Ma and lasted to ∼250 Ma. North of the Lanalhue fault, Late Paleozoic magmatic arc granitoids are nearly 100 km closer to the present day Andean trench than further south. We hypothesize that this marked difference in paleo-forearc width is due to an Early Permian period of subduction erosion north of 38°S, contrasting with ongoing accretion further south, which kinematically triggered the evolution of the Lanalhue Fault Zone. Permo-Triassic margin segmentation was due to differential forearc accretion and denudation characteristics, and is now expressed in contrasting lithologies and metamorphic signatures in todays Andean forearc region north and south of the Lanalhue Fault Zone.

unque comparten patrones comunes con otras areas metropolitanas de America Latina, las transformaciones de Santiago de Chile tienen como rasgo distintivo los profundos cambios de orden politico, economico y regulatorio que se han ido produciendo desde finales de la decada de los setenta, muchos de los cuales no tienen precedente en otras ciudades de Latinoamerica. El transporte urbano, precisamente, ha estado de manera frecuente en la palestra internacional desde el tiempo en que el gobierno militar dic-taminara la experiencia unica en el mundo de desregulacion total del sistema, durante los anos ’70. Las correcciones introducidas mas tarde, en democracia, a traves de sistemas competitivos de otorgamiento de concesiones, tambien crearon un hito en la experiencia mundial y, especialmente, latinoamericana, por lo innovador y profundo de las practicas adoptadas y por los resultados obte-nidos. Transantiago fue concebido en medio de la misma expectativa nacional e internacional y sus resultados tambien han dado la vuelta al mundo. Sin embargo, en este caso ellos han sorprendido por lo inesperados y por lo profundamente ne-gativos.Las causas de los problemas de Transantiago tienen muchas vertientes. No obstante, en su ori-gen se encuentran una serie de aspectos vinculados a la organizacion institucional y a las soluciones de gobernabilidad, que desde ya se constituyen como aspectos limitantes de la gestion, y cuyos efectos se veran con posterioridad. De esta manera, esta nota analiza las variables institucionales de Transantiago desde dos puntos de vista. Por una parte, las ca-pacidades de gestion y organizacion institucional sectorial y, por otra, las limitantes en la gestion y la institucionalidad territorial.

In south-central Chile (36–42° S), the western edge of South America has evolved as an active margin since the Pennsylvanian (∼305 Ma). Active margins are considered as sites of both potential continental growth and continental destruction. Continental growth in a margin setting can proceed by accretionary offscraping of juvenile material from the oceanic plate and by magmatic additions, whereas net mass loss can be achieved by subducting continental material, delamination, and chemical weathering. In southcentral Chile, margin evolution was never interrupted by island-arc accretion or continental collision. Thus, the area provides an excellent field laboratory for studying mass flux through a long-term, persistent, convergent-margin system.

Forearc accretionary wedges are cyclic systems in which material is frontally and/or basally accreted. Material cycling involves underthrusting, subduction, underplating, exhumation, erosion, transfer to the trench and underthrusting again. In this study we present a novel, tectonochronologic approach to constrain long-term exhumation rates of basally accreted wedge complexes, based on isotopic dating of structural features, on petrological data and sandbox analogue simulations. Congruence between the structural inventory in nature and structures generated in scaled sandbox experiments allows detailed insights into wedge dynamics. For the present-day surface material of the paleoaccretionary wedge of South-Central Chile (Valdivia area, 40°S), published U–Pb ages of detrital zircon place a maximum age of ∼278 Ma for subduction. Prograde metamorphism at transitional greenschist to blueschist facies conditions (420 °C, 8–9 kbar) was immediately followed by progressive penetrative deformation associated with basal accretion, dated at ∼250–245 Ma using Rb/Sr internal mineral isochrons. The accretion process involved duplex tectonics and antiformal stacking, with formation of near-horizontal mylonitic shear zones at around 241 Ma. Continuous basal accretion at depth gave rise to an extensional tectonic regime at higher structural levels. Both semi-ductile, small-scale extensional shear zones and post-kinematic vein mineralizations yield Rb/Sr ages of ∼235 Ma. Tension gashes, representing the latest isotopically dateable stage of structural evolution, were formed at ∼210 Ma, at conditions of ∼230 °C at 1.5–3 kbar, as constrained by fluid inclusion data. Zircon fission track data indicate final cooling to below ∼200 °C at 186±24 Ma. The results suggest continuous basal accretion for at least 50 Ma, with long-term average exhumation rates of 0.6±0.2 mm/a, most probably outbalanced by similar long-term average erosion rates. Changing plate boundary conditions at about 210–200 Ma terminated the accretion process, as evident from a dramatic decrease of exhumation rates at that time. Since then, the paleoaccretionary wedge remained stably in place despite its delicate geotectonic position within the Andean active margin. The tectonochronologic approach complements thermochronologic and geomorphologic methods of exhumation research as it provides direct constraints on mass flux rates even for high-temperature increments of P–T trajectories.

This paper presents new insights on the evolution of continental crust in a segment of the southern Central Andes (Chile–Argentina; ca. 36–41 °S) from compositional and isotopic age data of metamorphic and magmatic rocks. The crustal reservoir of this long-standing active continental margin is characterized by the isotopic composition of Paleozoic (meta)sedimentary rocks which is typical of Proterozoic continental crust (Nd model ages 1.6–2.1 Ga; isotopic composition at ca. 300 Ma, the time of formation of the late Paleozoic granites: 87Sr/86Sr ca. 0.71–0.72; 143Nd/144Nd ca. 0.5117–0.5120; 207Pb/204Pb ca. 15.64–15.70, 206Pb/204Pb ca. 18.2–18.6, 208Pb/204Pb ca. 37.2–38.5). The late Paleozoic and late Triassic granitoids (ca. 220 Ma) contain 30–80% of this material assuming a mantle endmember with the isotopic composition of Pacific MORB. The proposed mechanism of magma generation in the late Paleozoic and Triassic granitoids is assimilation of crustal material by mantle derived melts, i.e. mixing between crustal and mantle melts. The isotopic composition of the Paleozoic rocks in the southern Central Andes indicates a coherent evolution of the western Gondwana margin (21–41°S) during the Paleozoic mainly recycling Proterozoic material by sedimentation, metamorphism and magmatism. The magmatism of the Andean cycle represents important additions of juvenile material to the crust. The Mesozoic to Tertiary intrusions have a relatively uniform isotopic composition (87Sr/86Sri ca. 0.7036–0.7066; 143Nd/144Ndi ca. 0.5125–0.5129; Pbi 207Pb/204Pb ca. 15.60–15.65, 206Pb/204Pb ca. 18.0–18.5, 208Pb/204Pb ca. 37.2–38.4) indicating only small contributions of the crustal reservoir (ca. 5–10%) to mantle derived magma with presumed MORB isotope signature. The proposed main mechanism of crustal contribution in these rocks is mixing of continent-derived sediments into the mantle wedge.

This chapter explores the critical issue of measuring sustainable urban development (SUD) via the use of indicators. The chapter begins by situating indicators within the broader urban planning process, showing how they help measure goals and objectives, define evaluation criteria and monitor progress. Recognizing the inherent complexity of the sustainability concept, the chapter then presents the hierarchy of information generally used, in the measurement process. Several different approaches and techniques for measuring sustainability — via indicators and indices — are presented, and building on these precedents, the sustainable indicator prism is proposed as a means for structurally guiding and understanding the informational and geographical scales implicit in the multidimensionality of sustainable urban development (SUD). The chapter recognizes that a “one-size-fits-all” approach to SUD indicators is not possible; key challenges include the lack of responsible authority and the lack of place-specific data. Ultimately, indicators must reflect political reality, information availability and a relevant scale of analysis.

Background: Penicillin and third generation cephalosporin resistant pneumococcal isolates have emerged in Chile, mainly in the pediatric population. These isolates complicate therapeutic alternatives, specially among patients with central nervous system infections. Aim: To assess the frequency of penicillin and third generation cephalosporin resistance among isolates obtained from pediatric patients with invasive pneumococcal infections, and to study serotypes and clinical risk factors associated with resistance. Material and methods: Microbiological isolates obtained from children between April 1994 and May 1999 with pneumococcal invasive infections, were serotyped and analyzed according to their susceptibility to penicillin and cefotaxime by E-test and broth microdilution testing. Potential risk factors studied included patient's age, previous antibiotic use or admissions, comorbidity, and serotypes. Results: Seventy eight patients were studied. Penicillin-resistant pneumococcal isolates were detected in 35.9% of cases (21.8% with intermediate and 14.1% with high level resistance) without significant variation among different clinical conditions. Most of the high level penicillin-resistant pneumoccocal isolates had MIC ≥4 µg/mL (8 out of 11 strains). One third of penicillin-resistant isolates also expressed cefotaxime resistance. Multivariate analysis indicated an age ≤36 months (OR=6.8; IC 95%: 1.4 to 33.5) and serotype 14 (OR=6.3; IC 95%: 1.7 to 23.3) as factors associated with penicillin resistance. Conclusions: One third of the invasive pneumococcal isolates obtained from pediatric patients were resistant to penicillin. Risk factors involved a younger age and pneumococcal isolates belonging to serotype 14 (Rev Méd Chile 2002; 130: 26-34)