Transformaciones culturales y cambios climáticos en los Pirineos catalanes entre el Tardiglaciar y Holoceno antiguo : Aziliense y Sauveterriense en Balma de la Margineda y Balma Guilanyà

La información disponible para asentamientos prehistóricos de montaña de la vertiente sur de los Pirineos sugiere una estrecha relación entre los cambios climáticos del Tardiglacial-Holoceno y las transformaciones culturales de los cazadores-recolectores. En este artículo pretendemos analizar el significado de esas variaciones pioneras que se detectan en la vertiente suroriental del Pirineo, registradas en la Balma de la Margineda y Balma Guilanyà, entre las cronozonas Bölling-Alleröd y BorealThe available data from southern Pyrenees mountain settlements suggest a close relationship between Late Glacial and Early Holocene climate and cultural changes in hunter-gatherers lifestyle. In this paper we analyze the significance of these pioneer transformations detected in Balma de la Margineda and Balma Guilanyà between the Bölling-Alleröd and Boreal chronozone

The Metropolis and Evangelical Life: Coherence and Fragmentation in the ‘Lost City of London’

This article examines the interplay of different processes of cultural and subjective fragmentation experienced by conservative evangelical Anglicans, based on an ethnographic study of a congregation in central London. The author focuses on the evangelistic speaking practices of members of this church to explore how individuals negotiate contradictory norms of interaction as they move through different city spaces, and considers their response to tensions created by the demands of their workplace and their religious lives. Drawing on Georg Simmel’s ‘The Metropolis and Mental Life’, the author argues that their faith provides a sense of coherence and unity that responds to experiences of cultural fragmentation characteristic of everyday life in the city, while simultaneously leading to a specific consciousness of moral fragmentation that is inherent to conservative evangelicalism

Primary deficiency of interleukin-1 receptor-associated kinase (IRAK-4) presenting as fatal pseudomonas aeruginosa bacteremia in two siblings

Interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency is a primary immunodeficiency of innate immunity. This is the case of a previous healthy toddler and his sibling, who both died of fulminant sepsis due to Pseudomonas aeruginosa. Subsequent genetic analysis demonstrated IRAK-4 deficiency with compound heterozygous splice mutations. Fulminant fatal Pseudomonas aeruginosa sepsis may be the first manifestation of IRAK-4 deficiency

La montagne comme modèle d’enregistrement des mutations « culturelles » précoces : les cas de l’Azilien et du Sauveterrien en Pyrénées catalanes

Les Pyrénées ne comptent que quatre sites établis autour de 1 000 m qui peuvent témoigner de l’occupation de l’étage montagnard avant le Néolithique ancien. À partir des vallées d’Andorre et sur le flanc sud de la chaîne orientale, les abris de Guilanya et Margineda permettent d’analyser les mutations environnementales et les évolutions dans la culture matérielle et spirituelle des groupes de chasseurs-collecteurs de la fin du Tardiglaciaire à l’Holocène ancien. Au côté d’originalités culturelles (incursion d’Aziliens du versant nord pendant l’Alleröd, Sauveterriens sans microlithes cantonnés dans les Pyrénées sèches), les innovations techniques bien cernées en stratigraphie sont plus précocement attestées au cœur de la chaîne axiale qu’en bordure du littoral et dans les piémonts où certains décalages techno-typologiques, tel l’Épimagdalénien, ont été individualisés.In the Pyrenees, mountain settlements higher than 1000 m are scarce before the Early Neolithic. Balma Guilanyà and Balma Margineda, rock-shelters located in the south-eastern face of the Pyrenees, allow analyzing the ecological and the hunter-gatherer adaptations along the limit Late Glacial/Early Holocene. In this area, some cultural processes (like the sudden apparition of the Azilian from the north Pyrenees in the Allerød, or the development of a Sauveterrien stage without standardized microlithic artifacts in the south Pyrenees) suggest that these technical innovation are detected sooner in the core of the mountain chain than in peripheral areas as the piedmont or the coast, where some techno-typological endurances (Epimagdalenian) has been recognized

Desarrollo histórico de la especialidad Ortodoncia en Sancti Spíritus

Fundamento: En la provincia Sancti Spíritus se constató la ausencia de evidencias documentales de la historia de la especialidad Ortodoncia, por lo que es necesario un estudio para rescatar información que contribuya al patrimonio científico cubano en ciencias de la salud, asimismo para la formación del potencial humano actual y futuro. Objetivo: Describir el desarrollo histórico de la especialidad Ortodoncia en la provincia Sancti Spíritus. Metodología: Se realizó una investigación cualitativa con el uso de métodos teóricos: histórico-lógico, analítico-sintético y empíricos: entrevista y análisis documental, en el período comprendido entre 1980 y 2018. Resultados: Desde el surgimiento de la especialidad en la provincia hasta 1999 se crearon instalaciones de salud para realizar la atención de Ortodoncia en la localidad, lo que potencializado por la creación del grupo y el capítulo, permitió la formación de los primeros especialistas a pesar de las limitaciones materiales. En un segundo momento hasta la actualidad se perfeccionó el plan de estudios, se extendieron los servicios a todos los municipios y se incrementó la producción científica (reconocimientos, premios, participación en eventos nacionales e internacionales y publicaciones). Conclusiones: La especialidad ha tenido un desarrollo progresivo en la provincia en la medida que se ha fortalecido el claustro de profesores, con una formación estable del capital humano que cubre las necesidades de atención de la población en el territorio y con resultados científico-técnicos que avalan su alto nivel actual. La descripción de su evolución histórica permite perfeccionar la formación de las futuras generaciones y profundizar en otras temáticas como la gestión de la calidad

The field high-amplitude SX Phe variable BL Cam: results from a multisite photometric campaign. II. Evidence of a binary - possibly triple - system

Short-period high-amplitude pulsating stars of Population I ($\delta$ Sct stars) and II (SX Phe variables) exist in the lower part of the classical (Cepheid) instability strip. Most of them have very simple pulsational behaviours, only one or two radial modes being excited. Nevertheless, BL Cam is a unique object among them, being an extreme metal-deficient field high-amplitude SX Phe variable with a large number of frequencies. Based on a frequency analysis, a pulsational interpretation was previously given. aims heading (mandatory) We attempt to interpret the long-term behaviour of the residuals that were not taken into account in the previous Observed-Calculated (O-C) short-term analyses. methods heading (mandatory) An investigation of the O-C times has been carried out, using a data set based on the previous published times of light maxima, largely enriched by those obtained during an intensive multisite photometric campaign of BL Cam lasting several months. results heading (mandatory) In addition to a positive (161 $\pm$ 3) x 10$^{-9}$ yr$^{-1}$ secular relative increase in the main pulsation period of BL Cam, we detected in the O-C data short- (144.2 d) and long-term ($\sim$ 3400 d) variations, both incompatible with a scenario of stellar evolution. conclusions heading (mandatory) Interpreted as a light travel-time effect, the short-term O-C variation is indicative of a massive stellar component (0.46 to 1 M_{\sun}) with a short period orbit (144.2 d), within a distance of 0.7 AU from the primary. More observations are needed to confirm the long-term O-C variations: if they were also to be caused by a light travel-time effect, they could be interpreted in terms of a third component, in this case probably a brown dwarf star ($\geq$ 0.03 \ M_{\sun}), orbiting in $\sim$ 3400 d at a distance of 4.5 AU from the primary.Comment: 7 pages, 5 figures, accepted for publication in A&

Family Relationship, Water Contact and Occurrence of Buruli Ulcer in Benin

Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities. This case control study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU). The study involved 416 participants, of which 104 BU-confirmed cases and 312 age, gender and village of residence matched controls (persons who had no signs or symptoms of active or inactive BU). The results confirmed that contact with natural water sources is a risk factor. Furthermore, it suggests that a combination of genetic factors may constitute risk factors for the development of BU, possibly by influencing the type of immune response in the individual, and, consequently, the development of BU infection per se and its different clinical forms. These findings may be of major therapeutic interest

Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents

PURPOSEThere is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders.METHODSAfter a review of existing combination trial methodologies, regulatory requirements, and current results, a consensus among stakeholders was achieved.RESULTSCombinations of anticancer therapies should be developed on the basis of mechanism of action and robust preclinical evaluation, and may include data from adult clinical trials. The general principle for combination early-phase studies is that, when possible, clinical trials should be dose- and schedule-confirmatory rather than dose-exploratory, and every effort should be made to optimize doses early. Efficient early-phase combination trials should be seamless, including dose confirmation and randomized expansion. Dose evaluation designs for combinations depend on the extent of previous knowledge. If not previously evaluated, limited evaluation of monotherapy should be included in the same clinical trial as the combination. Randomized evaluation of a new agent plus standard therapy versus standard therapy is the most effective approach to isolate the effect and toxicity of the novel agent. Platform trials may be valuable in the evaluation of combination studies. Patient advocates and regulators should be engaged with investigators early in a proposed clinical development pathway and trial design must consider regulatory requirements.CONCLUSIONAn optimized, agreed approach to the design and evaluation of early-phase pediatric combination trials will accelerate drug development and benefit all stakeholders, most importantly children and adolescents with cancer.</p

[(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma

BACKGROUND: To compare morphological gross tumor volumes (GTVs), defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of (18)F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning. METHODS: Nineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV union or logical sum BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed. RESULTS: Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (p = 0.9), CTVs (mean 57.8 +/- 30.4 cm(3)) were significantly larger than BTVs (mean 42.1 +/- 24.4 cm(3); p &lt; 0.01) or GTVs (mean 38.7 +/- 25.7 cm(3); p &lt; 0.01). In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended &gt;or= 10 and 20 mm from the margin of the gadolinium enhancement. CONCLUSION: Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients