The first probe of a FLASH proton beam by PET.

The recently observed FLASH effect related to high doses delivered with high rates has the potential to revolutionize radiation cancer therapy if promising results are confirmed and an underlying mechanism understood. Comprehensive measurements are essential to elucidate the phenomenon. We report the first-ever demonstration of measurements of successive in-spill and post-spill emissions of gammas arising from irradiations by a FLASH proton beam. A small positron emission tomography (PET) system was exposed in an ocular beam of the Proton Therapy Center at MD Anderson Cancer Center to view phantoms irradiated by 3.5 × 1010protons with a kinetic energy of 75.8 MeV delivered in 101.5 ms-long spills yielding a dose rate of 164 Gy s-1. Most in-spill events were due to prompt gammas. Reconstructed post-spill tomographic events, recorded for up to 20 min, yielded quantitative imaging and dosimetric information. These findings open a new and novel modality for imaging and monitoring of FLASH proton therapy exploiting in-spill prompt gamma imaging followed by post-spill PET imaging.

The first PET glimpse of a proton FLASH beam.

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8 MeV and an intensity of about 3.5 × 1010protons that were extracted over 101.5 ms-long spills. The radiation environment was characterized by cadmium-zinc-telluride and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantom, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.

Development of secretome-based strategies to improve cell culture protocols in tissue engineering.

Advances in skin tissue engineering have promoted the development of artificial skin substitutes to treat large burns and other major skin loss conditions. However, one of the main drawbacks to bioengineered skin is the need to obtain a large amount of viable epithelial cells in short periods of time, making the skin biofabrication process challenging and slow. Enhancing skin epithelial cell cultures by using mesenchymal stem cells secretome can favor the scalability of manufacturing processes for bioengineered skin. The effects of three different types of secretome derived from human mesenchymal stem cells, e.g. hADSC-s (adipose cells), hDPSC-s (dental pulp) and hWJSC-s (umbilical cord), were evaluated on cultured skin epithelial cells during 24, 48, 72 and 120 h to determine the potential of this product to enhance cell proliferation and improve biofabrication strategies for tissue engineering. Then, secretomes were applied in vivo in preliminary analyses carried out on Wistar rats. Results showed that the use of secretomes derived from mesenchymal stem cells enhanced currently available cell culture protocols. Secretome was associated with increased viability, proliferation and migration of human skin epithelial cells, with hDPSC-s and hWJSC-s yielding greater inductive effects than hADSC-s. Animals treated with hWJSC-s and especially, hDPSC-s tended to show enhanced wound healing in vivo with no detectable side effects. Mesenchymal stem cells derived secretomes could be considered as a promising approach to cell-free therapy able to improve skin wound healing and regeneration.

Ceftobiprole: a clinical view.

Ceftobiprole is a broad-spectrum, fifth-generation cephalosporin currently approved for community-acquired and non-ventilator-associated hospital-acquired pneumonia. High bactericidal and anti-biofilm activity has been exhibited in in vitro and animal models. This, together with its synergism with other antibiotics against gram-positive bacteria, makes it an ideal candidate for treatment of complex infections, such as those associated with devices or infective endocarditis. More clinical data are needed to achieve drug positioning.

Distal edge determination precision for a multi-slat prompt-gamma camera: A comprehensive simulation and optimization of the detection system.

Multi-slat prompt-gamma camera is a promising tool for range monitoring during proton therapy. We report the results of a comprehensive simulation study analyzing the precision which is possible to reach with this camera in determination of the position of the distal edge of the Bragg peak. For the first time we include simulation of optical photons. The proton beam (single pencil beam, 130 MeV, 10 ns bunch period, total of 1·108 protons) is interacting with a polymethyl methacrylate (PMMA) phantom, which is a cylinder of 200 mm in diameter and length. The prompt gamma rays generated in the phantom are collimated with a multi-slat collimator and detected using a combination of yttrium aluminum perovskite (YAP) scintillators, installed in the collimator apertures, and light sensors. Two scintillator packing schemes, with one and with two scintillator plates per aperture, are considered. The collimator configuration (the septal thickness, aperture and height), resulting in the best precision, is determined using two methods of detector optimization. Precision of 2.1 mm (full width at half maximum) in the edge position determination is demonstrated.

Estudio cualitativo sobre sujetos de vida violenta en Venezuela desde la perspectiva generacional / Qualitative Study on Subjects with Violent Lives in Venezuela from a Generational Perspective / Estudo qualitativo sobre s de uma perspectiva geracional

Resumen Con base en la premisa teórica de que tanto el aumento de la inseguridad ciudadana, y de la violencia en general, como la ineficiente reacción institucional formal para regular las conductas sociales, tuvieron un efecto en la estructura de socialización e interacción individual del venezolano, el presente estudio hace un análisis comparativo generacional entre sujetos de vida violenta. Se expone la manera como la violencia se ha convertido en un valor de socialización y moralización para estos sujetos, quienes han centralizado la misma como un valor de vida para la interacción cotidiana con los demás individuos e instituciones. Al emplear una metodología cualitativa, a través de historias de vida, entrevistas a profundidad y revisión documental, los hallazgos permiten concluir que, como consecuencia de una socialización primaria y secundaria precaria (caracterizada por el establecimiento de vínculos débiles, en el plano afectivo y moral, con figuras como los padres, la familia, la sociedad, las instituciones y la autoridad), para el sujeto de vida violenta de la nueva generación la violencia pasó a ser un valor central, moralizado y legitimado. Estos sujetos tienen una mayor propensión a la violencia, la cual se configura no solo como su modo de vida, sino también como su rol principal para las relaciones con los demás y con las estructuras sociales.

Abstract Based on the theoretical premise that both an increase in citizen insecurity and general violence, as well as inefficient formal reactions by institutions regulating social conducts, affected Venezuelans' social and individual interaction structures, this study performs a generational comparative analysis between subjects with violent lives. The study shows how violence has become a value of social interaction and moralization for these subjects, who have centralized violence as a life value for daily interactions with other individuals and institutions. By using a qualitative methodology through life stories, in-depth interviews and documentary review, the findings allow concluding that, as a consequence of primary and secondary unstable social interaction (characterized by establishing weak emotional and moral bonds with figures, such as parents, family, society, institutions and authorities), violence became a central, moralized and legitimized value for subjects with violent lives in the new generation. These subjects are more likely to have a violent behavior, which is demonstrated not just by their ways of life, but in the main role violence plays in their relationships with others and social structures.

Resumo Partindo da premissa teórica de que tanto o aumento da insegurança cidadã e da violência em geral, quanto a ineficiente atuação institucional formal para regular os comportamentos sociais, tiveram um efeito na estrutura de socialização e interação individual dos sujeitos venezuelanos, este estudo faz uma análise comparativa geracional entre sujeitos de vida violenta. Expõe-se a forma como a violência se tornou um valor de socialização e moralização para esses sujeitos, que a centralizaram como um valor de vida para a interação cotidiana com outros indivíduos e instituições. Adotando uma metodologia qualitativa, por meio de histórias de vida, entrevistas em profundidade e revisão documental, os resultados permitem concluir que, em decorrência de uma precária socialização primária e secundária (caracterizada pelo estabelecimento de laços fracos, no plano afetivo e moral, com figuras como pais, família, sociedade, instituições e autoridade), para o sujeito da vida violenta da nova geração, a violência tornou-se um valor central, moralizado e legitimado. Esses sujeitos apresentam maior propensão à violência, que se configura não apenas como seu modo de vida, mas também como seu principal papel nas relações com os outros e com as estruturas sociais.

Estudio cualitativo sobre sujetos de vida violenta en Venezuela desde la perspectiva generacional / Estudo qualitativo sobre sujeitos de vida violenta na Venezuela a partir de uma perspectiva geracional / Qualitative Study on Subjects with Violent Lives in Venezuela from a Generational Perspective

Con base en la premisa teórica de que tanto el aumento de la inseguridad ciudadana, y de la violencia en general, como la ineficiente reacción institucional formal para regular las conductas sociales, tuvieron un efecto en la estructura de socialización e interacción individual del venezolano, el presente estudio hace un análisis comparativo generacional entre sujetos de vida violenta. Se expone la manera como la violencia se ha convertido en un valor de socialización y moralización para estos sujetos, quienes han centralizado la misma como un valor de vida para la interacción cotidiana con los demás individuos e instituciones. Al emplear una metodología cualitativa, a través de historias de vida, entrevistas a profundidad y revisión documental, los hallazgos permiten concluir que, como consecuencia de una socialización primaria y secundaria precaria (caracterizada por el establecimiento de vínculos débiles, en el plano afectivo y moral, con figuras como los padres, la familia, la sociedad, las instituciones y la autoridad), para el sujeto de vida violenta de la nueva generación la violencia pasó a ser un valor central, moralizado y legitimado. Estos sujetos tienen una mayor propensión a la violencia, la cual se configura no solo como su modo de vida, sino también como su rol principal para las relaciones con los demás y con las estructuras sociales.

Based on the theoretical premise that both an increase in citizen insecurity and general violence, as well as inefficient formal reactions by institutions regulating social conducts, affected Venezuelans' social and individual interaction structures, this study performs a generational comparative analysis between subjects with violent lives. The study shows how violence has become a value of social interaction and moralization for these subjects, who have centralized violence as a life value for daily interactions with other individuals and institutions. By using a qualitative methodology through life stories, in-depth interviews and documentary review, the findings allow concluding that, as a consequence of primary and secondary unstable social interaction (characterized by establishing weak emotional and moral bonds with figures, such as parents, family, society, institutions and authorities), violence became a central, moralized and legitimized value for subjects with violent lives in the new generation. These subjects are more likely to have a violent behavior, which is demonstrated not just by their ways of life, but in the main role violence plays in their relationships with others and social structures.

Partindo da premissa teórica de que tanto o aumento da insegurança cidadã e da violência em geral, quanto a ineficiente atuação institucional formal para regular os comportamentos sociais, tiveram um efeito na estrutura de socialização e interação individual dos sujeitos venezuelanos, este estudo faz uma análise comparativa geracional entre sujeitos de vida violenta. Expõe-se a forma como a violência se tornou um valor de socialização e moralização para esses sujeitos, que a centralizaram como um valor de vida para a interação cotidiana com outros indivíduos e instituições. Adotando uma metodologia qualitativa, por meio de histórias de vida, entrevistas em profundidade e revisão documental, os resultados permitem concluir que, em decorrência de uma precária socialização primária e secundária (caracterizada pelo estabelecimento de laços fracos, no plano afetivo e moral, com figuras como pais, família, sociedade, instituições e autoridade), para o sujeito da vida violenta da nova geração, a violência tornou-se um valor central, moralizado e legitimado. Esses sujeitos apresentam maior propensão à violência, que se configura não apenas como seu modo de vida, mas também como seu principal papel nas relações com os outros e com as estruturas sociais.

Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade.

OBJECTIVES: During the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. METHODS: Data from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006-7 cohort study was performed between October 2006 and March 2007, and the 2016-17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. RESULTS: Overall, 1262 episodes of BSI were included, 563 (44.6%) in 2006-7 and 699 (55.3%) in 2016-17. Multivariate models selected the following changes in patients' features in 2016-17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01-1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26-0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71-0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32-0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18-8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03-8.86). CONCLUSIONS: We found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.

Cu-BTC Functional Microdevices as Smart Tools for Capture and Preconcentration of Nerve Agents.

Cu-based metal-organic framework (MOF) microdevices are applied in sampling and preconcentration of nerve agents (NAs) diluted in gaseous streams. An in situ electrochemical-assisted synthesis of a Cu-benzene-1,3,5-tricarboxylate (BTC) thick film is carried out to functionalize a Cu-modified glass substrate. This simple, rapid, reproducible, and easy-to-integrate MOF synthesis approach enables the microfabrication of functional micro-preconcentrators with a large Brunauer-Emmett-Teller (BET) surface area (above 2000 cm2) and an active pore volume (above 90 nL) for the efficient adsorption of nerve agent molecules along the microfluidic channel 2.5 cm in length. The equilibrium adsorption capacity of the bulk material has been characterized through thermogravimetric analysis after exposure to controlled atmospheres of a sarin gas surrogate, dimethyl methylphosphonate (DMMP), in both dry and humid conditions (30% RH at 293 K). Breakthrough tests at the ppm level (162 mg/m3) reveal equilibrium adsorption capacities up to 691 mg/g. The preconcentration performance of such µ-devices when dealing with highly diluted surrogate atmosphere, i.e., 520 ppbV (2.6 mg/m3) at 298 K, leads to preconcentration coefficients up to 171 for sample volume up to 600 STP cm3. We demonstrate the potentialities of Cu-BTC micro-preconcentrators as smart first responder tools for "on-field" detection of nerve agents in the gas phase at relevant conditions.

Use of a mobile application for self-management of pancreatic enzyme replacement therapy is associated with improved gastro-intestinal related quality of life in children with Cystic Fibrosis.

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback. METHODS: A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module). RESULTS: One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p< 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p < 0.001). CONCLUSIONS: The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms.

Debate teórico sobre el proceso de instalación de una cultura de la violencia en Venezuela / Debate teórico sobre el proceso de instalación de una cultura de la violencia en Venezuela / Debate teórico sobre o processo de instalação de uma cultura da violência em Venezuela

Resumen El presente trabajo busca como objetivo analizar y debatir teóricamente los cambios sociales y las respuestas a estos en Venezuela. Estos cambios sociales afectaron directamente los procesos sociales en los que la violencia se incluyó dentro de la dinámica e interacción social y moral general de la sociedad venezolana, presentándose para el individuo como una conducta válida para relacionarse con las demás personas y con la estructura social en general. Por lo tanto, se propone la discusión teórica en la que se amplíen e interpreten las nociones de diferentes disciplinas, para sostener que en Venezuela este proceso social de asimilación de la violencia en la dinámica social general conllevó a la instalación de una Cultura de la Violencia y esta al mismo tiempo, retroalimentó a la acción violenta extendiéndola tanto cualitativa como cuantitativamente en la sociedad venezolana. Se concluye que diferentes factores sociales e institucionales produjeron una falla en el sistema a social venezolano para sostener la validez de la norma y la conducta cultural e institucionalmente aceptable. Como consecuencia, la violencia ingresó a la estructura social y, al no ser sancionada efectivamente, se legitimó como una conducta aceptable para la obtención de gratificaciones sociales, mientras que al mismo tiempo se deslegitimaron las instituciones, provocando que la violencia se presentará como una acción social aceptada para el individuo e incluso para las mismas instituciones, promoviéndose así, una generación de individuos socialmente más proclives a la violencia.

Abstract The current work aims to analyze and debate theoretically the social changes and the responses to these in Venezuela. These social changes directly affected the social processes in which violence was included within the social dynamics and interaction and general moral of Venezuelan society, presenting itself to the individual as a valid behavior to relate to other people and to the social structure in general. Therefore, the theoretical discussion is proposed in which the notions of different disciplines are expanded and interpreted, in order to sustain that in Venezuela, this social process of assimilation of violence in the general social dynamic led to the installation of a Culture of Violence and this, at the same time, fed the violent action by extending it both qualitatively and quantitatively in Venezuelan society. It is concluded that different social and institutional factors produced a failure in Venezuelan social system to sustain the validity of the norm and culturally and institutionally acceptable behavior. As a consequence, violence entered the social structure and, not being effectively sanctioned, it was legitimized as an acceptable behavior for obtaining social gratifications, while at the same time institutions were delegitimized, causing violence to be presented as a socially accepted action for the individual and even for the same institutions, thus promoting a generation of individuals more socially prone to violence.

Resumo O presente trabalho procura como objetivo analisar e debater teoricamente as mudanças sociais e as respostas a estes na Venezuela. Estas mudanças sociais afetaram diretamente os processos sociais nos quais a violência foi incluída dentro da dinâmica e interação social e moral geral da sociedade venezuelana, se apresentando para o indivíduo como uma conduta válida para se relacionar com as demais pessoas e com a estrutura social em geral. Portanto, propõe-se uma discussão teórica na qual se ampliem e interpretem as noções de diferentes disciplinas, para sustentar que na Venezuela este processo social de assimilação da violência na dinámica social geral levou à instalação de uma Cultura da Violência e esta ao mesmo tempo, retroalimentou à ação violenta estendendo-a tanto qualitativa quanto quantitativamente na sociedade venezuelana. Conclui-se que diferentes fatores sociais e institucionais produziram uma falha no sistema social venezuelano para sustentar a validade da norma e a conduta cultural e institucionalmente aceitável. Como consequência, a violência ingressou à estrutura social e, ao não ser sancionada efetivamente, legitimou-se como uma conduta aceitável para a obtenção de gratificações sociais, enquanto que ao mesmo tempo deslegitimaram-se as instituições, provocando que a violência se apresentara como uma ação social aceitada para o indivíduo e incluso para as mesmas instituições, se promovendo assim, uma geração de indivíduos socialmente mais propensos à violência.

Is the bone tissue of the femoral neck demineralised in patients with hip fracture?

The aim of this study is to establish the falsifiability of the "osteoporotic hypothesis" for hip fracture, according to which the bone density and mineral composition of bone tissue in patients with hip fracture is poorer than when no such fracture is present, and that this circumstance is relevant to the occurrence of a fracture. The study population consisted of forty patients treated with arthroplasty. Twenty patients with femoral neck fracture and another twenty with hip osteoarthritis received the same diagnostic protocol and the same antibiotic, anaesthetic, surgical and antithrombotic prophylaxis. Levels of calcium (Ca), phosphorus (P) and vitamin D in blood, amongst other values, were determined, and five samples of bone tissue from the proximal femoral metaphysis were obtained and characterised by optical microscopy and microanalytical analysis. No statistically significant differences were observed between the two groups with respect to the trabecular number, area or thickness, or inter-trabecular distance. However, there were differences in the length of the trabeculae, which was greater in the patients with hip osteoarthritis (p = 0.002), but not when the groups were compared by gender. When compared by age, a greater inter-trabecular distance was observed in the patients aged over 75 years (p = 0.036) but there were no differences in the remaining parameters. Serum levels of Ca (p = 0.03), P (p < 0.01) and vitamin D (p < 0.01) were lower in the fracture group. In the quantitative microanalytical analysis, no significant differences were observed in bone levels of Ca or P or in the Ca/P index, nor was there any correlation between serum and levels of bone Ca or P (Ca-0.197:p = 0.314;P-0.274:p = 0.158).Multiple linear regression revealed no correlation between the diagnoses, vitamin D and bone levels of Ca or P. Despite the reduced serum levels of Ca and P in the patients with hip fracture, no correlation was observed with bone levels of Ca and P,which were similar in both groups. There were differences in the organic bone structure, in terms of length and inter-trabecular distance. For patients with osteoporosis, treatment should be aimed at increasing the synthesis of bone trabeculae to reinforce their structure. Nevertheless, no such treatment can prevent falls, and therefore no reduction in hip fractures amongst this population can be assured.

Prognostic factors in neoadjuvant treatment followed by surgery in stage IIIA-N2 non-small cell lung cancer: a multi-institutional study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE: To evaluate the prognostic factors associated with survival in patients treated with neoadjuvant treatment [chemoradiotherapy (CRT) or chemotherapy] followed by surgery (CRTS) in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). METHODS: A retrospective study was conducted of 118 patients diagnosed with stage T1-T3N2M0 NSCLC and treated with CRTS at 14 hospitals in Spain between January 2005 and December 2014. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was performed. RESULTS: Surgery consisted of lobectomy (74.5% of cases), pneumectomy (17.8%), or bilobectomy (7.6%). Neoadjuvant treatment was CRT in 62 patients (52.5%) and chemotherapy alone in 56 patients (47.5%). Median follow-up was 42.5 months (5-128 months). 5-year OS and PFS were 51.1% and 49.4%, respectively. The following variables were independently associated with worse OS and PFS: pneumonectomy (vs. lobectomy); advanced pathologic T stage (pT3 vs. pT0-pT2); and presence of persistent N2 disease (vs. ypN0-1) in the surgical specimen. CONCLUSIONS: In this sample of patients with stage IIIA-N2 NSCLC treated with CRTS, 5-year survival (both OS and PFS) was approximately 50%. After CRTS, the patients with the best prognosis were those whose primary tumour and/or mediastinal nodal metastases were downstaged after induction therapy and those who underwent lobectomy. These findings provide further support for neoadjuvant therapy followed by surgery in selected patients.

Neoadjuvant treatment followed by surgery versus definitive chemoradiation in stage IIIA-N2 non-small-cell lung cancer: A multi-institutional study by the oncologic group for the study of lung cancer (Spanish Radiation Oncology Society).

OBJECTIVES: The role of surgery in stage IIIA-N2 non-small cell lung cancer (NSCLC) is an actively debated in oncology. To evaluate the value of surgery in this patient population, we conducted a multi-institutional retrospective study comparing neoadjuvant chemoradiotherapy or chemotherapy plus surgery (CRTS) to definitive chemoradiotherapy (dCRT). MATERIAL AND METHODS: A total of 247 patients with potentially resectable stage T1-T3N2M0 NSCLC treated with either CRTS or dCRT between January 2005 and December 2014 at 15 hospitals in Spain were identified. A centralized review was performed to ensure resectability. A propensity score matched analysis was carried out to balance patient and tumor characteristics (n = 78 per group). RESULTS: Of the 247 patients, 118 were treated with CRTS and 129 with dCRT. In the CRTS group, 62 patients (52.5%) received neoadjuvant CRT and 56 (47.4%) neoadjuvant chemotherapy. Surgery consisted of either lobectomy (97 patients; 82.2%) or pneumonectomy (21 patients; 17.8%). In the matched samples, median overall survival (OS; 56 vs 29 months, log-rank p = .002) and progression-free survival (PFS; 46 vs 15 months, log-rank p < 0.001) were significantly higher in the CRTS group. This survival advantage for CRTS was maintained in the subset comparison between the lobectomy subgroup versus dCRT (OS: 57 vs 29 months, p < 0.001; PFS: 46 vs 15 months, p < 0.001), but not in the comparison between the pneumonectomy subgroup and dCRT. CONCLUSION: The findings reported here indicate that neoadjuvant chemotherapy or chemoradiotherapy followed by surgery (preferably lobectomy) yields better OS and PFS than definitive chemoradiotherapy in patients with resectable stage IIIA-N2 NSCLC.

Una mirada a la desigualdad social y la violencia delictiva en Venezuela / A glance at social inequality and criminal violence in Venezuela / Uma olhada sobre a desigualdade social e a violência criminal na Venezuela

Resumen En los últimos años, en Venezuela se ha asistido a una reducción de la desigualdad social, pero los niveles de violencia delictiva se han incrementado en forma significativa. Con el objetivo de estudiar esta relación se propone la presente investigación, en la que, con base en una metodología complementaria, se correlacionaron los niveles de desigualdad social, medida a través del Índice Gini y la tasa de homicidio en una serie cronológica de más de diez años; de igual manera, se trabajó con la historia de vida de dos casos con patrones delictivos diferenciados. Los resultados de la correlación cuantitativa muestran que la reducción de la desigualdad social está relacionada con el incremento de los homicidios, al contrario de lo que indica la experiencia de otros países, mientras que en la exploración cualitativa se encuentra que no es la desigualdad social, estructuralmente hablando, lo que motiva o inhibe la conducta delictiva y violenta en el individuo. Más bien son las percepciones individuales, que se construyen desde dicha situación de igualdad o desigualdad, lo que cataliza tales acciones. Se concluye que la relación entre desigualdad social y violencia tiene un eco muy profundo en las percepciones individuales, que, al final de cuentas, retroalimentan la construcción estructural entre estas dos variables.

Abstract In Venezuela, in the few past years, a reduction in social inequality has been witnessed while, in contrast, criminal violence levels have gone up in a signifi cant manner. With the objective of studying such an ambivalent relations hip, this research is offered as based on a supplementary methodology where a correlation has been established between the levels of social inequality, measured through the Gini index and the homicide rate in chronological series of over more than ten years. Likewise, work was carried out on the life story of two cases with differentiated criminal patterns. The results of the quantitative correlation show that the social inequality reduction seen here is connected with the rising homicide rate. This is contrary to what the experience in other countries has indicated, while in qualitative exploration it was found that, structurally speaking, social inequality is not what either motivates or inhibits the criminal and violent conduct of individuals. but rather the individual perceptions constructed from the equality or inequality situation as catalyzers of these actions. The conclusion is that the relationship between social inequality and violence has a deep echo in these perceptions since, ultimately, they are e latter since they are ultimately what feeds back the structural construction existing between these two variables.

Resumo Nos últimos anos, a Venezuela tem visto uma redução na desigualdade social, mas os níveis de violência criminal têm aumentado significativamente. A fim de estudar esta relação a seguinte investigação é proposta, com base numa metodología complementar, os níveis de desigualdade social medidos pelo índice de Gini e a taxa de homicídio em uma série cronológica de dez anos foram correlacionados; do mesmo modo, nós trabalhamos com a história de vida de dois casos com diferentes padrões de criminalidade. Os resultados da correlação quantitativa mostram que a redução da desigualdade social está relacionada ao aumento no número de homicídios, contrário do que indica a experiencia de outros países, enquanto a exploração qualitativa é que não é a desigualdade social, estruturalmente falando, o que motiva ou inibe o comportamento criminoso e violento no indivíduo. Ao contrário, são percepções individuais, que são construídas a partir dessa situação de igualdade ou desigualdade, que catalisa tais ações. Conclui-se que a relação entre desigualdade social e violência tem um eco profundo nas percepções individuais, que, no final, retroalimentam a construção estrutural entre estas duas variáveis.

Dietary shifts have consequences for the repertoire of allergens produced by the European house dust mite.

Products manufactured from mass-cultured house dust mites, currently commercialized for the diagnosis and immunotherapy of allergy, are heterogeneous in terms of allergen composition and thus present concerns to regulatory authorities. The most abundant species, Dermatophagoides pteronyssinus (Trouessart) (Astigmata: Pyroglyphidae), produces 19 allergenic proteins. Many of these are putatively involved in mite digestive physiology and metabolism. This study aimed to evaluate the effects of mite-rearing media on allergen production. Mites were adapted to feed on culture media supplemented with proteins, lipids, carbohydrates or beard shavings, and collected to quantify major allergens (Der p 1 and 2) by immunodetection, transcription of allergen genes by real-time quantitative polymerase chain reaction, and allergen-related enzymatic activities. All culture media significantly affected the content of major allergens. Modification of macronutrients in the diet produced minor effects on the transcription of allergen genes, but significantly altered mite allergen-related activities. The most remarkable impacts were detected in mites feeding on beard shavings and were reflected in reductions in the content of major allergens, alterations in the transcription of nine allergen genes, and changes in eight allergen-related activities. These results demonstrate the importance of culture media to the quality and consistency of mite extracts used for pharmaceuticals, and highlight the need to further elucidate allergen production by mites in the laboratory and in domestic environments.

Efectos del encarcelamiento: una revisión de las medidas de prisionización en Venezuela / Effects of imprisonment: a review of prisonization measures in Venezuela / Efeitos do aprisionamento: uma revisão das medidas do prisionização na Venezuela

Resumen El objetivo Fue exponer y discutir, a la luz de la revisión teórica y empírica, los resultados aportados por las aplicaciones de la escala de prisionización venezolana, así como las variables asociadas a tal fenómeno. Empleando una metodología cuantitativa, con análisis estadístico bi y multivariado de la información tomada de una encuesta por muestreo, aplicada cara a cara a cuatro muestras de reclusos en tres años diferentes (2006, 2007 y 2009), se llegó a resultados que demuestran una validez y confiabilidad aceptable de la escala, la cual indica que en las muestras en estudio se verificaron altos niveles de prisionización, fenómeno que se veía profundizado en aquellos individuos con hábitos de consumo de sustancias ilícitas, antes y durante el encarcelamiento, y en menor medida mediante experiencias previas con la prisión y el sistema de justicia penal. La conclusión apunta a considerar que en el caso venezolano, la prisionización es un fenómeno que depende más del contexto institucional carcelario que de las variables individuales y sociales de los reclusos, y se plantea que el abordaje de dicho fenómeno debe profundizarse y repensarse en estudios que tomen en cuenta el "nuevo" régimen penitenciario venezolano.

Abstract The objective here was to expose and discuss, in the light of both theoretical and empirical, the results contributed through the application of the Venezuelan prisonization scale, as well as of the variables associated with such a phenomenon. By using a quantitative methodology, with a statistical bi and multivariate analysis of information taken from a sampling survey applied face to face four samples of inmates in three different years (2006, 2007 y 2009), results showing acceptable validity and reliability of the scale were reached, this indicating the verification of high levels of prisonization, a phenomenon that was being deepened in individuals with habits of illicit substance consumption prior to and during incarceration, and to a lesser extent through previous experiences with prison and the criminal justice system. The conclusion points to the consideration that, in the Venezuelan case, imprisonment is an occurrence depending rather from the prison institutional context than from inmates' individual and social variables, therefore the approach to this issue should be deepened and rethought in studies able to take into account the "new" Venezuelan penitentiary system.

Resumo O objetivo foi expor e discutir, à luz da revisão teórica e empírica, os resultados apresentados pelas aplicações da escala da prisionização venezuelana, assim como as variáveis associadas a tal fenômeno. Usando uma metodologia quantitativa, com análise estatística bi- e multi-variadou da informação pegada de uma pesquisa por amostra, aplicada cara a cara a quatro amostras de reclusos em três anos diferentes (2006, 2007 e 2009), obtiveram-se os resultados que demonstram uma validez e confiança aceitável da escala, que indica que nas amostras do estudo verificaram-se altos níveis de prisionização, fenômeno que era aprofundado naqueles indivíduos com hábitos do consumo de substâncias ilícitas, antes e durante o aprisionamento, e em menor medida por meio das experiências precedentes com a prisão e do sistema da justiça penal. A conclusão aponta considerar que no caso venezuelano, a prisionização é um fenômeno que dependa mais do contexto institucional da prisão que das variáveis individuais e sociais dos reclusos, e considera que a abordagem deste fenômeno deve ser aprofundado e repensado nos estudos que levem em conta o "novo" regime penitenciário venezuelano.

Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects.

177Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its ß- emission results in very efficient energy deposition in small-size tumours. Because of this, 177Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, 177mLu and 177Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The 177mLu/177Lu radionuclide generator provides a new production route for the therapeutic radionuclide 177Lu and can bring significant growth in the research and development of 177Lu based pharmaceuticals.

Effects of domestic chemical stressors on expression of allergen genes in the European house dust mite.

The expression of allergen genes in house dust mites is influenced by temperature and relative humidity, but little is known of the impacts of other environmental factors that may alter the repertoire of allergens released by mites in home microhabitats. Bioassays were conducted in concave microscope slides in combination with real-time quantitative polymerase chain reaction (RT-qPCR) to analyse gene expression of 17 allergens of Dermatophagoides pteronyssinus (Acariformes: Pyroglyphidae) exposed to three chemical stressors that can be present in domestic environments. Short-term exposure (5-12 days) to diesel exhaust particles (DEPs) (1 µg/cm2 ), bacterial lipopolysaccharide endotoxin (0.1 µg/cm2 ) and benzyl benzoate (3.2 µg/cm2 ), at concentrations exceeding those expected in homes, had no significant effect on allergen transcription. A significant increase in the transcription of allergens Der p 3, Der p 8 and Der p 21 was observed only after exposing mites to a higher concentration of DEPs (10 µg/cm2 ) over a whole generation. In combination, the present results suggest that the analysed factors have low impact on allergen production. The methodology described here offers a sound and rapid approach to the broad-spectrum study of factors affecting allergen-related mite physiology, and allows the simultaneous screening of different factors in a relatively short period with consideration of the full spectrum of allergen genes.