A test for comparing conditional ROC curves with multidimensional covariates.

The comparison of Receiver Operating Characteristic (ROC) curves is frequently used in the literature to compare the discriminatory capability of different classification procedures based on diagnostic variables. The performance of these variables can be sometimes influenced by the presence of other covariates, and thus they should be taken into account when making the comparison. A new non-parametric test is proposed here for testing the equality of two or more dependent ROC curves conditioned to the value of a multidimensional covariate. Projections are used for transforming the problem into a one-dimensional approach easier to handle. Simulations are carried out to study the practical performance of the new methodology. The procedure is then used to analyse a real data set of patients with Pleural Effusion to compare the diagnostic capability of different markers.

New vegetable varieties of Brassica rapa and Brassica napus with modified glucosinolate content obtained by mass selection approach.

Background: Glucosinolates (GSLs) constitute a characteristic group of secondary metabolites present in the Brassica genus. These compounds confer resistance to pests and diseases. Moreover, they show allelopathic and anticarcinogenic effects. All those effects are dependent on the chemical structure of the GSL. The modification of the content of specific GSLs would allow obtaining varieties with enhanced resistance and/or improved health benefits. Moreover, the attainment of varieties with the same genetic background but with divergent GSLs concentration will prompt the undertaking of studies on their biological effects. Objective and Methods: The objective of this study was to evaluate the efficacy of two divergent mass selection programs to modify GSL content in the leaves of two Brassica species: nabicol (Brassica napus L.), selected by glucobrassicanapin (GBN), and nabiza (Brassica rapa L.), selected by gluconapin (GNA) through several selection cycles using cromatographic analysis. Results: The response to selection fitted a linear regression model with no signs of variability depletion for GSL modification in either direction, but with higher efficiency in reducing the selected GSL than in the increasing. The selection was also effective in other parts of the plant, suggesting that there is a GSL translocation in the plant or a modification in their synthesis pathway that is not-organ specific. There was an indirect response of selection in other GSL; thus this information should be considered when designing breeding programs. Finally, populations obtained by selection have the same agronomic performance or even better than the original population. Conclusion: Therefore, mass selection seems to be a good method to modify the content of specific GSL in Brassica crops.

Reabsorción radicular apical externatras la ortodoncia: Factores clínicos ydiagnósticos y análisis de redes de genesrelacionados / External apical root resorption after orthodontic treatment: clinical and diagnostic factors and analysis of related gene networks

Introducción: La reabsorción radicular apical externa (EARR) provocada por las fuerzas ortodóncicas representa uno de los efectos iatrogénicos más indeseables del tratamiento. Se pretende establecer una relación entre las variables diagnósticas y clínicas del tratamiento con la aparición y severidad de la reabsorción radicular apical externa agresiva (aEARR). Adicionalmente, la red de interrelaciones genéticas sirve para la generación de hipótesis en la correlación de variaciones genéticas, previamente asociadas con aEARR, con otras enfermedades. Métodos: Se realizó un estudio de asociación mediante una selección de 240 pacientes clasificados en dos grupos, basándose en la presencia o ausencia de a EARR. Se realizó un análisis descriptivo y una regresión logística binaria condicional tipo backward entre las variables y el desarrollo de aEARR. Se seleccionaron 5 variantes (STAG2, RP1-30E17.2, P2RX7, SPP1 y TNFRSF11A) asociadas a una mayor predisposición al desarrollo de aEARR y se realizó un análisis de redes. Resultados: Exclusivamente la variable tiempo de tratamiento obtuvo resultados estadísticamente significativos (IC: 95%; p=0,007) en relación con la aEARR. En el análisis de redes se encontró relación de 4 variantes genéticas con diferentes etapas del proceso patológico de la EARR que se relacionaron con 6 patologías: artritis, osteoartrosis, enfermedad autoinmune, lupus eritematoso, hepatitis C y EARR. Conclusiones: El único factor que se asoció con una mayor prevalencia de aEARR es el tiempo de duración del tratamiento. Cualquier vía que pueda tener relación con el proceso inflamatorio y, por tanto, con el proceso reabsortivo, puede tener una implicación mayor/menor de manera directa o indirecta en el desarrollo de la EARR (AU)

Introduction: External apical root resorption (EARR) caused by orthodontic forces represents one of the most undesirable iatrogenic effects of treatment. The aim of this study is to establish a relation between the diagnostic and clinical variables of treatment with the appearance and severity of aggressive external apical root resorption (aEARR). Additionally, the network of genetic interrelationships offers the generation of hypotheses in the correlation of genetic variations, previously associated with aEARR, with other diseases. Methods: An association study was performed using a selection of 240 patients classified into two groups based on the presence or absence of aEARR. A descriptive analysis of the data along with a backward conditional binary logistic regression was performed between the variables and aEARR. Five variants (STAG2, RP1-30E17.2, P2RX7, SPP1 and TNFRSF11A) associated with an increased predisposition to aEARR were selected and network analysis was performed. Results: Only the treatment time variable obtained statistically significant results (CI: 95%; p=0.007) in relation to aEARR. In the network analysis, 4 genetic variants were found to be related to different stages of the pathological process of aEARR, which were associated with 6 pathologies: arthritis, osteoarthrosis, autoimmune disease, lupus erythematosus, hepatitis C and EARR. Conclusions: The only factor associated with a higher prevalence of aEARR is the treatment duration. Any pathway that may be related to the inflammatory process and therefore to the resorptive process may have a greater/lesser involvement directly or indirectly in the development of aEARR (AU)

Dermatomiositis paraneoplásica: a propósito de dos casos / Paraneoplastic dermatomyositis: report of two cases

La dermatomiositis es una miopatía inflamatoria con una incidencia de 0.5-1 caso por 100.000 habitantes. Se caracteriza por lesiones cutáneas típicas y debilidad muscular, aunque ocasionalmente podemos encontrar formas amiopáticas. La asociación con malignidad ha sido ampliamente descrita en la literatura, habiéndose detectado tumores hasta en un tercio de los casos. La presencia del anticuerpo anti-TIF-1-gamma presenta tasas más altas de neoplasia comparada con otras formas sin este anticuerpo, lo que obliga a realizar un despistaje tumoral. A continuación, presentamos 2 casos de dermatomiositis asociada a anticuerpo TIF-1-gamma asociadas a malignidad. (AU)

Dermatomyositis is an inflammatory myopathy with an incidence of 0.5-1 case per 100,000 inhabitants. It is characterized by hallmark cutaneus findings and muscle weakness, although we can occasionally find amyopathic forms. The association with malignancy has been widely described in the literature, as tumors have been detected in up to a third of the cases. The presence of the anti-TIF-1-gamma antibody presents higher rates of neoplasia compared to other forms without this antibody, so it is mandatory to do a tumor screening. Next, we present 2 cases of TIF-1-gamma antibody-associated dermatomyositis associated with malignancy. (AU)

Influencia de la dependencia del consumo de tabaco en el control de la presión arterial en personas con tratamiento farmacológico antihipertensivo / Influence of smoking dependence on blood pressure control in people on antihypertensive pharmacological therapy

Resumen: Tabaquismo e hipertensión son importantes factores de riesgo cardiovascular cuya relación sigue sin estar clara. Objetivo: comprobar si hay diferencias entre fumadores y no fumadores en los valores de presión arterial (PA) obtenida mediante medida en clínica, periodo de actividad, periodo nocturno, hipertensión de bata blanca, hipertensión enmascarada y perfil circadiano.Pacientes y métodos: muestreo oportunista consecutivo de personas con tratamiento farmacológico antihipertensivo que acudieron a dos farmacias comunitarias entre enero de 2013 y agosto de 2019.A todas ellas se les realizó medida aislada y monitorización ambulatoria de su presión arterial (MAPA) durante 24 horas. Resultados: la muestra estuvo constituida por 91 fumadores y 573 no fumadores de edad media 55,9 y 66,1 respectivamente, y porcentaje de hombres 64,8 % y 50,6 % también respectivamente.Los valores con diferencias significativas en paciente fumadores y no fumadores fueron los siguientes: presión arterial en periodo de actividad (PAS/PAD): 132/80 mmHg fumadores, 129/75 mmHg no fumadores. Hipertensos no controlados enmascarados: 13,2 % fumadores, 12,0 % no fumadores. Perfil no dipper: 34,0 % fumadores, 44,2 % no fumadores. Conclusiones: los fumadores tuvieron la presión arterial más alta en el periodo de actividad, más prevalencia de hipertensión no controlada enmascarada y de perfil dipper que los no fumadores, de forma estadísticamente significativa. (AU)

Servicio profesional de monitorización ambulatoria de la presión arterial (MAPA) en farmacia comunitaria. Identificación de hipertensión no controlada de bata blanca / Ambulatory Blood Pressure Monitoring (ABPM) professional service in Community Pharmacy. White-coat UnControlled Hypertension identification

Varón de 68 años diagnosticado de hipertensión arterial hace 6 meses.Desde ese momento lo hemos incluido en nuestro Servicio Profesional Farmacéutico Asistencial deMedida y Control de la presión arterial (PA). Los sucesivos valores de PA obtenidos mediante medida aisladaen farmacia comunitaria (MAFC) han estado dentro de la normalidad.Actualmente el paciente tiene programada una intervención quirúrgica en el servicio de oftalmologíaque no se ha podido realizar por presentar sucesivos valores elevados de PA (≥180/100 mmHg) en consultamédica de atención primaria y especializada.El paciente refiere ponerse “muy nervioso” al acudir al médico. Sospechamos que los valores elevadosde PA en consulta son compatibles con un “efecto de bata blanca” (EBB).Acordamos con él y su médica de atención primaria la realización de una monitorización ambulatoriade presión arterial (MAPA) con el objetivo de descartar el EBB.Una vez obtenidos los resultados, identificar el fenotipo del paciente y observar que los valores de PAde la MAPA están dentro de la normalidad, se realiza una interconsulta con oftalmología.A la vista de los resultados el oftalmólogo decide realizar la operación, que se lleva a cabo con éxito. (AU)

68-year-old man diagnosed with hypertension 6 months ago. We have included it in our professionalpharmaceutical care service for measurement and control of blood pressure, obtaining values withinnormality.The patient has scheduled a surgical intervention in the ophthalmology service that could not beperformed due to successive high blood pressure values (≥180 / 100 mmHg) in a primary and specializedmedical consultation.He refers to getting “very nervous” when going to the doctor. We suspect that elevated office BP valuesare compatible with a “white coat effect” (WCE). We agreed with him and his primary care physician toperform ambulatory blood pressure monitoring (ABPM) in order to rule out EBB.Once the results have been obtained, identify the patient’s phenotype and observe that the ABPM BPvalues are within normality, an ophthalmology consultation is performed.In view of them, the ophthalmologist decides to perform the operation, which is carried out successfully. (AU)

Estudio multicéntrico de la reparación endovascular urgente de la aorta torácica: indicaciones y resultados / A multicenter study of emergency endovascular repair of the thoracic aorta: indications and outcomes

Objetivo Las técnicas endovasculares se han convertido en una herramienta esencial para el tratamiento de la patología de aorta torácica descendente (TEVAR). El objetivo es analizar las indicaciones y resultados del TEVAR urgente a nivel nacional en relación con la cirugía programada. Diseño y ámbito de estudio Registro multicéntrico retrospectivo de pacientes con patología de aorta torácica descendente tratados de urgencia mediante técnicas endovasculares entre los años 2012-2016 en 11 servicios clínicos. Pacientes, criterios de inclusión 1) Aneurismas de aorta torácica rotos, 2) roturas traumáticas de aorta torácica y 3) disecciones de aorta torácica tipo B (DATBc) complicadas. Variables principales Mortalidad, supervivencia y tasa de reintervenciones. Variables secundarias Datos demográficos, factores de riesgo cardiovasculares, datos específicos por indicación, datos técnicos y complicaciones postoperatorias. Resultados Se obtuvieron 135 TEVAR urgentes (111 varones, edad media 60,4 ± 16,3 años): 43 aneurismas aórticos rotos (31,9%), 54 disecciones tipo B (40%) y 32 roturas aórticas traumáticas (23,7%) y otras etiologías 4,4%. La mortalidad global a los 30 días fue del 18,5%, siendo superior en los aneurismas de aorta torácica rotos (27,9%). La supervivencia media actuarial ha sido del 67± 6% a los 5 años. La tasa de ictus postoperatoria fue del 5,2% y la tasa de isquemia medular del 5,9%. Las reintervenciones aórticas fueron necesarias en 12 pacientes (9%). Conclusiones La patología de aorta descendente urgente puede ser tratada mediante técnicas endovasculares con resultados óptimos y baja morbimortalidad, aunque ligeramente superior a los casos electivos. Este registro aporta por primera vez, información de la realidad clínica diaria del TEVAR urgente en España. (AU)

Objective Endovascular techniques have become an essential tool for the treatment of descending thoracic aortic disease (thoracic endovascular aneurysm repair [TEVAR]). The aim is to analyze the indications and outcomes of emergency TEVAR at national level in relation to elective surgery. Study design and scope A retrospective multicenter registry of patients with descending thoracic aortic disease treated on an emergency basis using endovascular techniques between 2012-2016, in 11 clinical units. Patients, inclusion criteria 1) Ruptured descending thoracic aortic aneurysms; 2) Blunt traumatic thoracic aortic injury; and 3) Complicated acute type B aortic dissections (TBADc). Primary variables Patient mortality, survival and reoperation rate. Secondary variables Demographic data, cardiovascular risk factors, specific data by indication, technical resources and postoperative complications. Results A total of 135 urgent TEVARs were included (111 men, mean age 60.4 ± 16.3 years): 43 ruptured thoracic aortic aneurysms (31.9%), 54 type B dissections (40%) and 32 traumatic aortic injuries (23.7%), and other etiologies 4.4%. The overall mortality rate at 30 days was 18.5%, and proved higher in the ruptured descending thoracic aortic aneurysms group (27.9%). The mean actuarial survival rate was 67± 6% at 5 years. The postoperative stroke rate was 5.2%, and the paraplegia rate was 5.9%. Aortic reoperations proved necessary in 12 patients (9%). Conclusions Emergency descending thoracic aortic diseases can be treated by endovascular techniques with optimal results and low morbidity and mortality – though the figures are slightly higher than in elective cases. This registry provides, for the first time, real information on the daily clinical practice of emergency TEVAR in Spain. (AU)

A multicenter study of emergency endovascular repair of the thoracic aorta: Indications and outcomes.

OBJECTIVE: Endovascular techniques have become an essential tool for the treatment of descending thoracic aortic disease (thoracic endovascular aneurysm repair [TEVAR]). The aim is to analyze the indications and outcomes of emergency TEVAR at national level in relation to elective surgery. STUDY DESIGN AND SCOPE: A retrospective multicenter registry of patients with descending thoracic aortic disease treated on an emergency basis using endovascular techniques between 2012-2016, in 11 clinical units. PATIENTS, INCLUSION CRITERIA: 1) Ruptured descending thoracic aortic aneurysms (RTAA); 2) Blunt traumatic thoracic aortic injury (TAI); and 3) Complicated acute type B aortic dissections (TBADc). PRIMARY VARIABLES: Patient mortality, survival and reoperation rate. SECONDARY VARIABLES: Demographic data, cardiovascular risk factors, specific data by indication, technical resources and postoperative complications. RESULTS: A total of 135 urgent TEVARs were included (111 men, mean age 60.4 ±â€¯16.3 years): 43 ruptured thoracic aortic aneurysms (31.9%), 54 type B dissections (40%) and 32 traumatic aortic injuries (23.7%), and other etiologies 4.4%. The overall mortality rate at 30 days was 18.5%, and proved higher in the RTAA group (27.9%). The mean actuarial survival rate was 67 ±â€¯6% at 5 years. The postoperative stroke rate was 5.2%, and the paraplegia rate was 5.9%. Aortic reoperations proved necessary in 12 patients (9%). CONCLUSIONS: Emergency descending thoracic aortic diseases can be treated by endovascular techniques with optimal results and low morbidity and mortality - though the figures are slightly higher than in elective cases. This registry provides, for the first time, real information on the daily clinical practice of emergency TEVAR in Spain.

A multicenter study of emergency endovascular repair of the thoracic aorta: indications and outcomes. / Estudio multicéntrico de la reparación endovascular urgente de la aorta torácica: indicaciones y resultados.

OBJECTIVE: Endovascular techniques have become an essential tool for the treatment of descending thoracic aortic disease (thoracic endovascular aneurysm repair [TEVAR]). The aim is to analyze the indications and outcomes of emergency TEVAR at national level in relation to elective surgery. STUDY DESIGN AND SCOPE: A retrospective multicenter registry of patients with descending thoracic aortic disease treated on an emergency basis using endovascular techniques between 2012-2016, in 11 clinical units. PATIENTS, INCLUSION CRITERIA: 1) Ruptured descending thoracic aortic aneurysms; 2) Blunt traumatic thoracic aortic injury; and 3) Complicated acute type B aortic dissections (TBADc). PRIMARY VARIABLES: Patient mortality, survival and reoperation rate. SECONDARY VARIABLES: Demographic data, cardiovascular risk factors, specific data by indication, technical resources and postoperative complications. RESULTS: A total of 135 urgent TEVARs were included (111 men, mean age 60.4 ± 16.3 years): 43 ruptured thoracic aortic aneurysms (31.9%), 54 type B dissections (40%) and 32 traumatic aortic injuries (23.7%), and other etiologies 4.4%. The overall mortality rate at 30 days was 18.5%, and proved higher in the ruptured descending thoracic aortic aneurysms group (27.9%). The mean actuarial survival rate was 67± 6% at 5 years. The postoperative stroke rate was 5.2%, and the paraplegia rate was 5.9%. Aortic reoperations proved necessary in 12 patients (9%). CONCLUSIONS: Emergency descending thoracic aortic diseases can be treated by endovascular techniques with optimal results and low morbidity and mortality - though the figures are slightly higher than in elective cases. This registry provides, for the first time, real information on the daily clinical practice of emergency TEVAR in Spain.

Sub-clustering in skeletal class III malocclusion phenotypes via principal component analysis in a southern European population.

The main aim of this study was to generate an adequate sub-phenotypic clustering model of class III skeletal malocclusion in an adult population of southern European origin. The study design was conducted in two phases, a preliminary cross-sectional study and a subsequent discriminatory evaluation by main component and cluster analysis to identify differentiated skeletal sub-groups with differentiated phenotypic characteristics. Radiometric data from 699 adult patients of southern European origin were analyzed in 212 selected subjects affected by class III skeletal malocclusion. The varimax rotation was used with Kaiser normalization, to prevent variables with more explanatory capacity from affecting the rotation. A total of 21,624 radiographic measurements were obtained as part of the cluster model generation, using a total set of 55 skeletal variables for the subsequent analysis of the major component and cluster analyses. Ten main axes were generated representing 92.7% of the total variation. Three main components represented 58.5%, with particular sagittal and vertical variables acting as major descriptors. Post hoc phenotypic clustering retrieved six clusters: C1:9.9%, C2:18.9%, C3:33%, C4:3.77%, C5:16%, and C6:16%. In conclusion, phenotypic variation was found in the southern European skeletal class III population, demonstrating the existence of phenotypic variations between identified clusters in different ethnic groups.

Characterizing laser-plasma ion accelerators driving an intense neutron beam via nuclear signatures.

Compact, bright neutron sources are opening up several emerging applications including detection of nuclear materials for national security applications. At Los Alamos National Laboratory, we have used a short-pulse laser to accelerate deuterons in the relativistic transparency regime. These deuterons impinge on a beryllium converter to generate neutrons. During the initial experiments where these neutrons were used for active interrogation of uranium and plutonium, we observed ß-delayed neutron production from decay of 9Li, formed by the high-energy deuteron bombardment of the beryllium converter. Analysis of the delayed neutrons provides novel evidence of the divergence of the highest energy portion of the deuterons (i.e., above 10 MeV/nucleon) from the laser axis, a documented feature of the breakout afterburner laser-plasma ion acceleration mechanism. These delayed neutrons form the basis of non-intrusive diagnostics for determining the features of deuteron acceleration as well as monitoring neutron production for the next generation of laser-driven neutron sources.

Variability in the use of neuroimaging techniques for diagnosis and follow-up of stroke patients. / Grandes variaciones en la utilización de pruebas por imagen en el diagnóstico y seguimiento de los pacientes con ictus.

INTRODUCTION AND OBJECTIVE: Imaging diagnosis is essential for treatment planning in stroke patients. However, use of these techniques varies due to uncertainty about their effectiveness. Our purpose was to describe the use of CT and MRI in stroke and transient ischaemic attack (TIA) over 5years in hospitals belonging to the Canary Islands Health Service and analyse interhospital variability based on routinely collected administrative data. PATIENTS AND METHOD: We gathered the minimum basic dataset (MBDS) from patients diagnosed with stroke or TIA between 2005 and 2010 in 4hospitals. Patients' age, sex, procedures, secondary diagnoses, and duration of hospital stay were also recorded. We conducted a descriptive analysis of patient characteristics and a bivariate analysis using the t test and the chi square test to detect differences between patients assessed and not assessed with MRI. Logistic regression was used to analyse unequal access to MRI. RESULTS AND CONCLUSIONS: Our study included 10,487 patients (8,571 with stroke and 1,916 with TIA). The percentage of stroke patients undergoing a CT scan increased from 89.47% in 2005 to 91.50% in 2010. In these patients, use of MRI also increased from 25.41% in 2005 to 36.02% in 2010. Among patients with TIA, use of CT increased from 84.64% to 88.04% and MRI from 32.53% to 39.13%. According to our results, female sex, younger age, and presence of comorbidities increase the likelihood of undergoing MRI.

Anomalous material-dependent transport of focused, laser-driven proton beams.

Intense lasers can accelerate protons in sufficient numbers and energy that the resulting beam can heat materials to exotic warm (10 s of eV temperature) states. Here we show with experimental data that a laser-driven proton beam focused onto a target heated it in a localized spot with size strongly dependent upon material and as small as 35 µm radius. Simulations indicate that cold stopping power values cannot model the intense proton beam transport in solid targets well enough to match the large differences observed. In the experiment a 74 J, 670 fs laser drove a focusing proton beam that transported through different thicknesses of solid Mylar, Al, Cu or Au, eventually heating a rear, thin, Au witness layer. The XUV emission seen from the rear of the Au indicated a clear dependence of proton beam transport upon atomic number, Z, of the transport layer: a larger and brighter emission spot was measured after proton transport through the lower Z foils even with equal mass density for supposed equivalent proton stopping range. Beam transport dynamics pertaining to the observed heated spot were investigated numerically with a particle-in-cell (PIC) code. In simulations protons moving through an Al transport layer result in higher Au temperature responsible for higher Au radiant emittance compared to a Cu transport case. The inferred finding that proton stopping varies with temperature in different materials, considerably changing the beam heating profile, can guide applications seeking to controllably heat targets with intense proton beams.

Effectiveness of Biology-Based Methods for Inhibiting Orthodontic Tooth Movement. A Systematic Review.

INTRODUCTION: Several experimental studies in the literature have tested different biology-based methods for inhibiting or decreasing orthodontic tooth movement (OTM) in humans. This systematic review investigated the effects of these interventions on the rate of tooth movement. STUDY DESIGN: Electronic [MedLine; SCOPUS; Cochrane Library; OpenGrey;Web of Science] and manual searches were conducted up to January 26th, 2016 in order to identify publications of clinical trials that compared the decreasing or inhibiting effects of different biology-based methods over OTM in humans. A primary outcome (rate of OTM deceleration/inhibition) and a number of secondary outcomes were examined (clinical applicability, orthodontic force used, possible side effects). Two reviewers selected the studies complying with the eligibility criteria (PICO format) and assessed risk of bias [Cochrane Collaboration's tool]. Data collection and analysis were performed following the Cochrane recommendations. RESULTS: From the initial electronic search, 3726 articles were retrieved and 5 studies were finally included. Two types of biology-based techniques used to reduce the rate of OTM in humans were described: pharmacological and low-level laser therapy. In the first group, human Relaxin was compared to a placebo and administered orally. It was described as having no effect on the inhibition of OTM in humans after 32 days, while the drug tenoxicam, injected locally, inhibited the rate of OTM by up to 10% in humans after 42 days. In the second group, no statistically significant differences were reported, compared to placebo, for the rate of inhibition of OTM in humans after 90 days of observation when a 860 nm continuous wave GaAlA slow-level laser was used. CONCLUSIONS: The currently available data do not allow us to draw definitive conclusions about the use of various pharmacological substances and biology-based therapies in humans able to inhibit or decrease the OTM rate. There is an urgent need for more sound well-designed randomized clinical trials in the field.

Smart Release Nano-formulation of Cytochrome C and Hyaluronic Acid Induces Apoptosis in Cancer Cells.

Herein we tested a nanosized cancer-cell targeted delivery system based on cytochrome c (Cyt c) and hyaluronic acid. Cyt c was chosen since it is a per se non-toxic protein but causes apoptosis when delivered to the cytoplasm of target cells. Hyaluronic acid was employed to create the nanosized delivery system with passive targeting capability in order to exploit the enhanced permeation and retention (EPR) effect and active targeting capability of hyaluronic acid. In addition, our goal was to incorporate a smart release strategy to only promote protein release upon reaching its target. Nanoparticles were formed by a simple yet precise nanoprecipitation process based on desolvation. They were physically characterized to select precipitation conditions leading to adequate size, shape, protein bioactivity, and protein loading to produce a feasible targeted cancer treatment. We synthesized nanoparticles of around 500 nm diameter with a 60% protein loading and more than 80% of protein bioactivity. In vitro, cumulative release of 92% of Cyt c was observed after 8 h under conditions mimicking the reductive intracellular environment, while under non-denaturing conditions only 20% was released. The nanoparticles displayed a selective cytotoxic effect on cancer cells. After 6 h of incubation with the nanoparticles, hyaluronic acid receptor over expressing A549 human lung adenocarcinoma cells showed a viability of ca. 20% at 0.16 mg/ml of Cyt c concentration. Only a negligible effect was observed on viability of COS-7 African green monkey kidney fibroblast, a normal cell line notoverexpressing the hyaluronic acid receptor. Confocal microscopy confirmed that the drug delivery system indeed delivered Cyt c to the cytoplasm of the target cells. We conclude that we were able to create a smart stimuli-responsive targeted drug delivery system with significant potential in cancer therapy.

Linear dependence of surface expansion speed on initial plasma temperature in warm dense matter.

Recent progress in laser-driven quasi-monoenergetic ion beams enabled the production of uniformly heated warm dense matter. Matter heated rapidly with this technique is under extreme temperatures and pressures, and promptly expands outward. While the expansion speed of an ideal plasma is known to have a square-root dependence on temperature, computer simulations presented here show a linear dependence of expansion speed on initial plasma temperature in the warm dense matter regime. The expansion of uniformly heated 1-100 eV solid density gold foils was modeled with the RAGE radiation-hydrodynamics code, and the average surface expansion speed was found to increase linearly with temperature. The origin of this linear dependence is explained by comparing predictions from the SESAME equation-of-state tables with those from the ideal gas equation-of-state. These simulations offer useful insight into the expansion of warm dense matter and motivate the application of optical shadowgraphy for temperature measurement.

Visualization of expanding warm dense gold and diamond heated rapidly by laser-generated ion beams.

With the development of several novel heating sources, scientists can now heat a small sample isochorically above 10,000 K. Although matter at such an extreme state, known as warm dense matter, is commonly found in astrophysics (e.g., in planetary cores) as well as in high energy density physics experiments, its properties are not well understood and are difficult to predict theoretically. This is because the approximations made to describe condensed matter or high-temperature plasmas are invalid in this intermediate regime. A sufficiently large warm dense matter sample that is uniformly heated would be ideal for these studies, but has been unavailable to date. Here we have used a beam of quasi-monoenergetic aluminum ions to heat gold and diamond foils uniformly and isochorically. For the first time, we visualized directly the expanding warm dense gold and diamond with an optical streak camera. Furthermore, we present a new technique to determine the initial temperature of these heated samples from the measured expansion speeds of gold and diamond into vacuum. We anticipate the uniformly heated solid density target will allow for direct quantitative measurements of equation-of-state, conductivity, opacity, and stopping power of warm dense matter, benefiting plasma physics, astrophysics, and nuclear physics.

On the analysis of inhomogeneous magnetic field spectrometer for laser-driven ion acceleration.

We present a detailed study of the use of a non-parallel, inhomogeneous magnetic field spectrometer for the investigation of laser-accelerated ion beams. Employing a wedged yoke design, we demonstrate the feasibility of an in-situ self-calibration technique of the non-uniform magnetic field and show that high-precision measurements of ion energies are possible in a wide-angle configuration. We also discuss the implications of a stacked detector system for unambiguous identification of different ion species present in the ion beam and explore the feasibility of detection of high energy particles beyond 100 MeV/amu in radiation harsh environments.

Uniform heating of materials into the warm dense matter regime with laser-driven quasimonoenergetic ion beams.

In a recent experiment at the Trident laser facility, a laser-driven beam of quasimonoenergetic aluminum ions was used to heat solid gold and diamond foils isochorically to 5.5 and 1.7 eV, respectively. Here theoretical calculations are presented that suggest the gold and diamond were heated uniformly by these laser-driven ion beams. According to calculations and SESAME equation-of-state tables, laser-driven aluminum ion beams achievable at Trident, with a finite energy spread of ΔE/E∼20%, are expected to heat the targets more uniformly than a beam of 140-MeV aluminum ions with zero energy spread. The robustness of the expected heating uniformity relative to the changes in the incident ion energy spectra is evaluated, and expected plasma temperatures of various target materials achievable with the current experimental platform are presented.