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1.
Int J Drug Policy ; 123: 104274, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38065009

RESUMO

BACKGROUND: Illicit drug use is overrepresented in music festival attendees compared with the general population. Drug use often involves a wide range of substances with the potential to cause drug toxicity. Law enforcement-centred strategies intended to deter drug use and supply at these mass gatherings have been implemented throughout Australia. However, many have been criticised for their lack of effectiveness, with evidence suggesting that they can inadvertently increase the risk of drug harm. Drug deaths are often multifactorial, providing added challenges in the development of prevention strategies. This study aimed to determine the frequency of deaths involving alcohol and other drugs at music festivals in Australia and to identify potential risk factors that may inform future harm reduction strategies. METHODS: A descriptive case series study was conducted using the National Coronial Information System (NCIS) to investigate drug-related deaths at music festivals throughout Australia between 1 July 2000 (Queensland from 1 January 2001) and 31 December 2019, using a list of keywords comprising music festival names and terms. RESULTS: There were 64 deaths, of which most involved males (73.4%) aged in their mid-20s (range 15-50 years). Drug toxicity was the most common primary cause of death (46.9%) followed by external injuries (37.5%). The drug most commonly detected or reported as being used was MDMA (65.6%), followed by alcohol (46.9%) and cannabis (17.2%), with most cases reporting the use of two or more drugs (including alcohol) and 36% reporting a history of drug misuse in the coroner's findings. Most deaths were unintentional, with less than a fifth of cases (17.2%) involving intentional self-harm. Clinical intervention was involved in 64.1% of cases and most festivals occurred in inner city locations (59.4%). CONCLUSIONS: The findings suggest that drug-related deaths at music festivals in Australia typically involve young people using multiple illicit substances in combination with alcohol. Most are unintentional and could potentially be prevented through the implementation of a range of harm reduction strategies, including mobile medical care, drug checking services, and increased consumer education and awareness.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Drogas Ilícitas , Música , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Adolescente , Idoso , Drogas Ilícitas/efeitos adversos , Férias e Feriados , Austrália/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Etanol
2.
Drug Alcohol Depend ; 212: 108066, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32473536

RESUMO

BACKGROUND: Acute use of alcohol is a robust risk factor for suicide, reported in approximately one- to two-fifths of suicide cases. Comparisons of risk factors between suicides with and without prior acute alcohol consumption have not been investigated in Australia. This study addresses the gap by examining individual factors (age, sex, employment status, method of suicide) and environmental factors (month of death, jurisdiction) between alcohol and non-alcohol suicide. METHODS: Data for all suicide deaths (aged 15 and over) in Australia were obtained from the National Coronial Information System (NCIS). Blood alcohol concentrations (BAC) were extracted from coronial reports, along with demographic information. Alcohol consumption prior to suicide was assumed if BAC ≥ 0.05 g/100 mL. We compared case characteristics between alcohol related and non-alcohol related suicides using logistic regression. RESULTS: 26.7% of suicide deaths in Australia had a BAC ≥ 0.05 g/100 mL. Alcohol use prior to suicide was associated with male gender (adjusted odds ratio [AOR]: 1.14, 95% confidence interval [95%CI]: 1.03, 1.26), being aged between 35-44 years (AOR: 1.26, 95%CI: 1.08, 1.46) and hangings (AOR: 1.53, 95%CI: 1.08, 1.46). Mean suicides per month over the timeframe demonstrated significant seasonality. Mean counts per month for alcohol related suicides peaked in December, compared to a peak in September for non-alcohol related suicides. CONCLUSIONS: This study highlights differences between alcohol related and non-alcohol related suicides including sex, age, method of death, time of year and location within Australia. Targeting alcohol related suicide should be a key priority in comprehensive suicide prevention strategies.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/tendências , Estações do Ano , Suicídio/psicologia , Suicídio/tendências , Adolescente , Adulto , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/epidemiologia , Austrália/epidemiologia , Concentração Alcoólica no Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Adulto Jovem
3.
Nutr Metab Cardiovasc Dis ; 29(2): 152-158, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30642791

RESUMO

BACKGROUND AND AIMS: Diet is known to play a decisive role in the development of coronary heart disease (CHD). One factor believed to decrease lifetime risk of CHD is the consumption of omega-3 fatty acids. Yet, conclusive evidence regarding the potential cardioprotective effects of fatty acids is far from being reached. The present study aimed to provide further evidence on the association of serum fatty acid profiles with CHD risk. METHODS AND RESULTS: The CARdio-vascular Disease, Living and Ageing in Halle study (CARLA study) is an observational cohort study comprising an older adult's general population with a high level of cardiovascular risk factors. In a matched case-control design the serum fatty acid concentrations of 73 subjects with an incident fatal or nonfatal CHD event were compared to 146 controls matched for sex and age. Our data show that the participants of the CARLA study are underserved in unsaturated fatty acids with respect to current dietary recommendations. In addition, the ratio of omega-6 to omega-3 fatty acids was determined to be 8:1 which underlines the consumption of a Western-style diet enriched in omega-6 fatty acids. There were no significant differences in fatty acid patterns between cases and controls. Thus, no clear association of particular serum fatty acid levels with cardiovascular risk was found. CONCLUSION: Our results support the conclusion that in populations with a homogenous low level of omega-3 polyunsaturated fatty acids consumption, serum fatty acid levels are not associated with CHD risk.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Dieta Saudável , Ácidos Graxos Ômega-3/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Doença das Coronárias/diagnóstico , Doença das Coronárias/prevenção & controle , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo
4.
J Int Med Res ; 46(4): 1303-1310, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29332515

RESUMO

Sepsis is one of the most frequent causes of death among patients in intensive care units. Many therapeutic strategies have been assessed without the desired success rates. A key risk factor for death is hypotension due to vasodilatation with vascular hyposensitivity. However, the pathways underlying this process remain unclear. Endotoxemia induces inflammatory mediators, and this is followed by vasoplegia and decreased cardiac contractility. Although inhibition of these mediators diminishes mortality rates in animal models, this phenomenon has not been confirmed in humans. Downregulation of vasoconstrictive receptors such as angiotensin receptors, adrenergic and vasopressin receptors is seen in sepsis, which is associated with a hyporesponsiveness to vasoconstrictive mediators. Animal studies have verified that receptor downregulation is linked to the above-mentioned inflammatory mediators. Anti-inflammatory therapy with glucocorticoids reportedly improves responsiveness to catecholamines with higher survival in rats, although this has not been shown to be clinically significant in humans. Hence, there is an urgent need for in-depth studies investigating the underlying mechanisms of vasoplegia to allow for development of effective therapeutic strategies for the treatment of sepsis.


Assuntos
Choque Séptico/complicações , Vasoplegia/complicações , Animais , Humanos , Mediadores da Inflamação/metabolismo , Choque Séptico/fisiopatologia , Vasoconstrição , Vasoplegia/fisiopatologia
5.
Sci Rep ; 7: 45276, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28374744

RESUMO

Disorder remains a key limitation in the search for robust signatures of topological superconductivity in condensed matter. Whereas clean semiconducting quantum wires gave promising results discussed in terms of Majorana bound states, disorder makes the interpretation more complex. Quantum wires of 3D topological insulators offer a serious alternative due to their perfectly-transmitted mode. An important aspect to consider is the mixing of quasi-1D surface modes due to the strong degree of disorder typical for such materials. Here, we reveal that the energy broadening γ of such modes is much smaller than their energy spacing Δ, an unusual result for highly-disordered mesoscopic nanostructures. This is evidenced by non-universal conductance fluctuations in highly-doped and disordered Bi2Se3 and Bi2Te3 nanowires. Theory shows that such a unique behavior is specific to spin-helical Dirac fermions with strong quantum confinement, which retain ballistic properties over an unusually large energy scale due to their spin texture. Our result confirms their potential to investigate topological superconductivity without ambiguity despite strong disorder.

6.
Phys Med Biol ; 60(13): 5019-35, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26061457

RESUMO

The aim of this work was to improve the computational efficiency of Monte Carlo simulations when tracking protons through a proton therapy treatment head. Two proton therapy facilities were considered, the Francis H Burr Proton Therapy Center (FHBPTC) at the Massachusetts General Hospital and the Crocker Lab eye treatment facility used by University of California at San Francisco (UCSFETF). The computational efficiency was evaluated for phase space files scored at the exit of the treatment head to determine optimal parameters to improve efficiency while maintaining accuracy in the dose calculation. For FHBPTC, particles were split by a factor of 8 upstream of the second scatterer and upstream of the aperture. The radius of the region for Russian roulette was set to 2.5 or 1.5 times the radius of the aperture and a secondary particle production cut (PC) of 50 mm was applied. For UCSFETF, particles were split a factor of 16 upstream of a water absorber column and upstream of the aperture. Here, the radius of the region for Russian roulette was set to 4 times the radius of the aperture and a PC of 0.05 mm was applied. In both setups, the cylindrical symmetry of the proton beam was exploited to position the split particles randomly spaced around the beam axis. When simulating a phase space for subsequent water phantom simulations, efficiency gains between a factor of 19.9 ± 0.1 and 52.21 ± 0.04 for the FHTPC setups and 57.3 ± 0.5 for the UCSFETF setups were obtained. For a phase space used as input for simulations in a patient geometry, the gain was a factor of 78.6 ± 7.5. Lateral-dose curves in water were within the accepted clinical tolerance of 2%, with statistical uncertainties of 0.5% for the two facilities. For the patient geometry and by considering the 2% and 2mm criteria, 98.4% of the voxels showed a gamma index lower than unity. An analysis of the dose distribution resulted in systematic deviations below of 0.88% for 20% of the voxels with dose of 20% of the maximum or more.


Assuntos
Algoritmos , Terapia com Prótons/métodos , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Método de Monte Carlo , Dosagem Radioterapêutica
7.
Phys Med Biol ; 60(13): 5037-52, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26061583

RESUMO

The aim of this work was to develop a framework for modeling organ effects within TOPAS (TOol for PArticle Simulation), a wrapper of the Geant4 Monte Carlo toolkit that facilitates particle therapy simulation. The DICOM interface for TOPAS was extended to permit contour input, used to assign voxels to organs. The following dose response models were implemented: The Lyman-Kutcher-Burman model, the critical element model, the population based critical volume model, the parallel-serial model, a sigmoid-based model of Niemierko for normal tissue complication probability and tumor control probability (TCP), and a Poisson-based model for TCP. The framework allows easy manipulation of the parameters of these models and the implementation of other models. As part of the verification, results for the parallel-serial and Poisson model for x-ray irradiation of a water phantom were compared to data from the AAPM Task Group 166. When using the task group dose-volume histograms (DVHs), results were found to be sensitive to the number of points in the DVH, with differences up to 2.4%, some of which are attributable to differences between the implemented models. New results are given with the point spacing specified. When using Monte Carlo calculations with TOPAS, despite the relatively good match to the published DVH's, differences up to 9% were found for the parallel-serial model (for a maximum DVH difference of 2%) and up to 0.5% for the Poisson model (for a maximum DVH difference of 0.5%). However, differences of 74.5% (in Rectangle1), 34.8% (in PTV) and 52.1% (in Triangle) for the critical element, critical volume and the sigmoid-based models were found respectively. We propose a new benchmark for verification of organ effect models in proton therapy. The benchmark consists of customized structures in the spread out Bragg peak plateau, normal tissue, tumor, penumbra and in the distal region. The DVH's, DVH point spacing, and results of the organ effect models are provided. The models were used to calculate dose response for a Head and Neck patient to demonstrate functionality of the new framework and indicate the degree of variability between the models in proton therapy.


Assuntos
Terapia com Prótons/métodos , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Software , Benchmarking , Determinação de Ponto Final , Método de Monte Carlo , Dosagem Radioterapêutica
8.
Am J Transplant ; 14(12): 2723-35, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25363083

RESUMO

Primary T cell activation and effector cell differentiation is required for rejection of allogeneic grafts in naïve recipients. It has become evident, that mitochondria play an important role for T cell activation. Expression of several mitochondrial proteins such as TCAIM (T cell activation inhibitor, mitochondrial) is down-regulated upon T cell receptor triggering. Here we report that TCAIM inhibited spontaneous development of memory and effector T cells. CD4(+) T cells from Tcaim knock-in (KI) mice showed reduced activation, cytokine secretion and proliferation in vitro. Tcaim KI T cells tolerated allogeneic skin grafts upon transfer into Rag-1 KO mice. CD4(+) and CD8(+) T cells from these mice did not infiltrate skin grafts and kept a naïve or central memory phenotype, respectively. They were unable to acquire effector phenotype and functions. TCAIM altered T cell activation-induced mitochondrial distribution and reduced mitochondrial reactive oxygen species (mROS) production. Thus, TCAIM controls T cell activation and promotes tolerance induction probably by regulating TCR-mediated mitochondrial distribution and mROS production.


Assuntos
Ativação Linfocitária/imunologia , Mitocôndrias/imunologia , Proteínas Mitocondriais/fisiologia , Transplante de Pele , Linfócitos T Reguladores/imunologia , Linfócitos T/imunologia , Tolerância ao Transplante/imunologia , Animais , Diferenciação Celular , Células Cultivadas , Citocinas/metabolismo , Citometria de Fluxo , Proteínas de Homeodomínio/fisiologia , Memória Imunológica/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T/metabolismo , Transplante Homólogo
9.
Pol J Vet Sci ; 17(1): 47-52, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24724469

RESUMO

The present paper provides new experimental data on the biochemical and haematological profile of blood in pheasant hens, and points out the changes in both biochemical and haematological parameters that occur during the laying period. Significant effects of egg laying on both the biochemical and the haematological blood parameters of pheasant hens were found. Biochemical analyses revealed a significant increase in the metabolites cholesterol, uric acid, lactate, the enzyme aspartate aminotransferase (AST) and the minerals calcium and phosphorous, as well as a significant decrease in total protein, albumin and glucose in the course of the laying period. Haematological analyses revealed a significant increase in the count of leukocytes, lymphocytes, eosinophils, basophils and monocytes due to egg laying. In addition, the erythrocyte count and haemoglobin content significantly decreased in the middle of the laying period and then rebounded at the end of the laying period. The haematocrit content gradually decreased till the end of the laying period. All together, the results of this study underline the impact of the reproduction status of pheasant hens on basic blood parameters. The biochemical and haematological values presented in this study may be of help in assessing disease conditions in laying pheasant hens.


Assuntos
Análise Química do Sangue/veterinária , Galliformes/fisiologia , Oviposição/fisiologia , Animais , Feminino , Galliformes/sangue , Valores de Referência
10.
J Anim Physiol Anim Nutr (Berl) ; 98(6): 1013-20, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24628699

RESUMO

Canine atopic dermatitis (CAD) is an inflammatory skin disorder that is characterized by pruritus and associated cutaneous changes. Treatment interventions include allergen avoidance, allergen-specific immunotherapy as well as a symptomatic therapy using glucocorticoids and antihistamines. In addition, a dietary intervention using polyunsaturated fatty acids (PUFA) has been shown to alleviate symptoms in some dogs. Although the beneficial effects of PUFA in the treatment of CAD have been known for several years, their mode of action remains unclear. This review discusses the evidential basis of the therapeutic use of dietary PUFA in the treatment of CAD. Particular emphasis will be placed on the role of cutaneous mast cells. In addition, recent evidence from in vitro studies on the regulation of mast cell exocytosis will be used to build a mechanistic model of the active principle of PUFA. It is proposed that dietary PUFA are integrated into mast cell membranes resulting in a reorganization of membrane microdomains. This may then be accompanied by functional changes of membrane-associated proteins such as the phospholipases D (PLD), enzymes having an important impact on mast cell exocytosis processes.


Assuntos
Dermatite Atópica/veterinária , Doenças do Cão/tratamento farmacológico , Ácidos Graxos Insaturados/uso terapêutico , Mastócitos/efeitos dos fármacos , Ração Animal , Animais , Dermatite Atópica/tratamento farmacológico , Suplementos Nutricionais , Cães , Mastócitos/metabolismo
11.
Med Phys ; 40(12): 121719, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24320505

RESUMO

PURPOSE: TOPAS (TOol for PArticle Simulation) is a particle simulation code recently developed with the specific aim of making Monte Carlo simulations user-friendly for research and clinical physicists in the particle therapy community. The authors present a thorough and extensive experimental validation of Monte Carlo simulations performed with TOPAS in a variety of setups relevant for proton therapy applications. The set of validation measurements performed in this work represents an overall end-to-end testing strategy recommended for all clinical centers planning to rely on TOPAS for quality assurance or patient dose calculation and, more generally, for all the institutions using passive-scattering proton therapy systems. METHODS: The authors systematically compared TOPAS simulations with measurements that are performed routinely within the quality assurance (QA) program in our institution as well as experiments specifically designed for this validation study. First, the authors compared TOPAS simulations with measurements of depth-dose curves for spread-out Bragg peak (SOBP) fields. Second, absolute dosimetry simulations were benchmarked against measured machine output factors (OFs). Third, the authors simulated and measured 2D dose profiles and analyzed the differences in terms of field flatness and symmetry and usable field size. Fourth, the authors designed a simple experiment using a half-beam shifter to assess the effects of multiple Coulomb scattering, beam divergence, and inverse square attenuation on lateral and longitudinal dose profiles measured and simulated in a water phantom. Fifth, TOPAS' capabilities to simulate time dependent beam delivery was benchmarked against dose rate functions (i.e., dose per unit time vs time) measured at different depths inside an SOBP field. Sixth, simulations of the charge deposited by protons fully stopping in two different types of multilayer Faraday cups (MLFCs) were compared with measurements to benchmark the nuclear interaction models used in the simulations. RESULTS: SOBPs' range and modulation width were reproduced, on average, with an accuracy of +1, -2 and ±3 mm, respectively. OF simulations reproduced measured data within ±3%. Simulated 2D dose-profiles show field flatness and average field radius within ±3% of measured profiles. The field symmetry resulted, on average in ±3% agreement with commissioned profiles. TOPAS accuracy in reproducing measured dose profiles downstream the half beam shifter is better than 2%. Dose rate function simulation reproduced the measurements within ∼2% showing that the four-dimensional modeling of the passively modulation system was implement correctly and millimeter accuracy can be achieved in reproducing measured data. For MLFCs simulations, 2% agreement was found between TOPAS and both sets of experimental measurements. The overall results show that TOPAS simulations are within the clinical accepted tolerances for all QA measurements performed at our institution. CONCLUSIONS: Our Monte Carlo simulations reproduced accurately the experimental data acquired through all the measurements performed in this study. Thus, TOPAS can reliably be applied to quality assurance for proton therapy and also as an input for commissioning of commercial treatment planning systems. This work also provides the basis for routine clinical dose calculations in patients for all passive scattering proton therapy centers using TOPAS.


Assuntos
Método de Monte Carlo , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Espalhamento de Radiação , Humanos , Garantia da Qualidade dos Cuidados de Saúde , Radiometria , Dosagem Radioterapêutica
12.
Phys Rev Lett ; 110(18): 186806, 2013 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-23683235

RESUMO

Quantum coherent transport of surface states in a mesoscopic nanowire of the three-dimensional topological insulator Bi(2}Se(3) is studied in the weak-disorder limit. At very low temperatures, many harmonics are evidenced in the Fourier transform of Aharonov-Bohm oscillations, revealing the long phase coherence length of spin-chiral Dirac fermions. Remarkably, from their exponential temperature dependence, we infer an unusual 1/T power law for the phase coherence length L(φ)(T). This decoherence is typical for quasiballistic fermions weakly coupled to their environment.

13.
Med Phys ; 39(11): 6818-37, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23127075

RESUMO

PURPOSE: While Monte Carlo particle transport has proven useful in many areas (treatment head design, dose calculation, shielding design, and imaging studies) and has been particularly important for proton therapy (due to the conformal dose distributions and a finite beam range in the patient), the available general purpose Monte Carlo codes in proton therapy have been overly complex for most clinical medical physicists. The learning process has large costs not only in time but also in reliability. To address this issue, we developed an innovative proton Monte Carlo platform and tested the tool in a variety of proton therapy applications. METHODS: Our approach was to take one of the already-established general purpose Monte Carlo codes and wrap and extend it to create a specialized user-friendly tool for proton therapy. The resulting tool, TOol for PArticle Simulation (TOPAS), should make Monte Carlo simulation more readily available for research and clinical physicists. TOPAS can model a passive scattering or scanning beam treatment head, model a patient geometry based on computed tomography (CT) images, score dose, fluence, etc., save and restart a phase space, provides advanced graphics, and is fully four-dimensional (4D) to handle variations in beam delivery and patient geometry during treatment. A custom-designed TOPAS parameter control system was placed at the heart of the code to meet requirements for ease of use, reliability, and repeatability without sacrificing flexibility. RESULTS: We built and tested the TOPAS code. We have shown that the TOPAS parameter system provides easy yet flexible control over all key simulation areas such as geometry setup, particle source setup, scoring setup, etc. Through design consistency, we have insured that user experience gained in configuring one component, scorer or filter applies equally well to configuring any other component, scorer or filter. We have incorporated key lessons from safety management, proactively removing possible sources of user error such as line-ordering mistakes. We have modeled proton therapy treatment examples including the UCSF eye treatment head, the MGH stereotactic alignment in radiosurgery treatment head and the MGH gantry treatment heads in passive scattering and scanning modes, and we have demonstrated dose calculation based on patient-specific CT data. Initial validation results show agreement with measured data and demonstrate the capabilities of TOPAS in simulating beam delivery in 3D and 4D. CONCLUSIONS: We have demonstrated TOPAS accuracy and usability in a variety of proton therapy setups. As we are preparing to make this tool freely available for researchers in medical physics, we anticipate widespread use of this tool in the growing proton therapy community.


Assuntos
Método de Monte Carlo , Terapia com Prótons/métodos , Neoplasias Oculares/diagnóstico por imagem , Neoplasias Oculares/radioterapia , Humanos , Melanoma/diagnóstico por imagem , Melanoma/radioterapia , Medicina de Precisão , Terapia com Prótons/instrumentação , Radiocirurgia , Dosagem Radioterapêutica , Espalhamento de Radiação , Software , Tomografia Computadorizada por Raios X
14.
J Biol Regul Homeost Agents ; 26(3): 357-66, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23034255

RESUMO

Th17 cells are potent pro-inflammatory effectors crucial for defense against extracellular bacteria. However, in this context and in the context of autoimmune disorders Th17 cells have been demonstrated to be key contributors to destructive pathological mechanism. A number of trials report TGF-beta to be involved in Th17 cell development. Nevertheless, to date, the role that TGF-beta plays in Th17 cell generation remains unclear. In this paper we highlight the role of TGF-beta in Th17 cell development in the mouse. The effects of likewise T cell specific over-expression of TGF-beta or inhibition of TGF-beta signal transduction in these cells on Th17 cell development were investigated by means of transgenic mouse models. The T cell specific insensitivity to TGF-beta does not prevent Th17 cell development ex vivo or in vitro in the murine system. In contrast, stimulation of T cells over-expressing TGF-beta actually results in decreased Th17 cell numbers in comparison to the wild type. Thus, our data indicate that TGF-beta signaling in T cells is dispensable or even inhibitory for generation of Th17 cells in the mouse. Moreover, we could show TGF-beta to inhibit a LPS driven Th1 cell development suggesting the cytokine to act as an indirect effector in Th17 cell differentiation.


Assuntos
Diferenciação Celular/imunologia , Transdução de Sinais/imunologia , Células Th17/imunologia , Fator de Crescimento Transformador beta/imunologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Transgênicos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Células Th1/citologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/citologia , Células Th17/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
15.
Phys Rev Lett ; 109(5): 057005, 2012 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-23006203

RESUMO

We have studied the dependence of the superconducting (SC) transition temperature on the mutual orientation of magnetizations of Fe1 and Fe2 layers in the spin valve system CoO(x)/Fe1/Cu/Fe2/Pb. We find that this dependence is nonmonotonic when passing from the parallel to the antiparallel case and reveals a distinct minimum near the orthogonal configuration. The analysis of the data in the framework of the SC triplet spin valve theory gives direct evidence for the long-range triplet superconductivity arising due to noncollinearity of the two magnetizations.

16.
Nanotechnology ; 23(25): 255701, 2012 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-22652540

RESUMO

Magnetotransport of individual rolled-up Fe(3)Si nanomembranes is investigated in a broad temperature range from 4.2 K up to 300 K in pulsed magnetic fields up to 55 T. The observed magnetoresistance (MR) has the following pronounced features: (i) MR is negative in the investigated intervals of temperature and magnetic field; (ii) its magnitude increases linearly with the magnetic field in a low-field region and reveals a gradual trend to saturation when the magnetic field increases; (iii) the MR effect becomes more pronounced with increasing temperature. These dependences of MR on the magnetic field and temperature are in line with predictions of the spin-disorder model of the spin-flip s-d interaction assisted with creation or annihilation of magnons, which is expected above a certain critical temperature. Comparison of the MR features in rolled-up and planar samples reveals a substantial increase of the critical temperature in the rolled-up tube, which is attributed to a new geometry and internal strain arising in the rolled-up nanomembranes, influencing the electronic and magnetic properties of the material.

17.
Phys Med Biol ; 57(11): 3281-93, 2012 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-22572154

RESUMO

A key task within all Monte Carlo particle transport codes is 'navigation', the calculation to determine at each particle step what volume the particle may be leaving and what volume the particle may be entering. Navigation should be optimized to the specific geometry at hand. For patient dose calculation, this geometry generally involves voxelized computed tomography (CT) data. We investigated the efficiency of navigation algorithms on currently available voxel geometry parameterizations in the Monte Carlo simulation package Geant4: G4VPVParameterisation, G4VNestedParameterisation and G4PhantomParameterisation, the last with and without boundary skipping, a method where neighboring voxels with the same Hounsfield unit are combined into one larger voxel. A fourth parameterization approach (MGHParameterization), developed in-house before the latter two parameterizations became available in Geant4, was also included in this study. All simulations were performed using TOPAS, a tool for particle simulations layered on top of Geant4. Runtime comparisons were made on three distinct patient CT data sets: a head and neck, a liver and a prostate patient. We included an additional version of these three patients where all voxels, including the air voxels outside of the patient, were uniformly set to water in the runtime study. The G4VPVParameterisation offers two optimization options. One option has a 60-150 times slower simulation speed. The other is compatible in speed but requires 15-19 times more memory compared to the other parameterizations. We found the average CPU time used for the simulation relative to G4VNestedParameterisation to be 1.014 for G4PhantomParameterisation without boundary skipping and 1.015 for MGHParameterization. The average runtime ratio for G4PhantomParameterisation with and without boundary skipping for our heterogeneous data was equal to 0.97: 1. The calculated dose distributions agreed with the reference distribution for all but the G4PhantomParameterisation with boundary skipping for the head and neck patient. The maximum memory usage ranged from 0.8 to 1.8 GB depending on the CT volume independent of parameterizations, except for the 15-19 times greater memory usage with the G4VPVParameterisation when using the option with a higher simulation speed. The G4VNestedParameterisation was selected as the preferred choice for the patient geometries and treatment plans studied.


Assuntos
Método de Monte Carlo , Terapia com Prótons , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Neoplasias/radioterapia , Dosagem Radioterapêutica , Fatores de Tempo
18.
Phys Med Biol ; 57(11): 3295-308, 2012 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-22572201

RESUMO

A general method for handling time-dependent quantities in Monte Carlo simulations was developed to make such simulations more accessible to the medical community for a wide range of applications in radiotherapy, including fluence and dose calculation. To describe time-dependent changes in the most general way, we developed a grammar of functions that we call 'Time Features'. When a simulation quantity, such as the position of a geometrical object, an angle, a magnetic field, a current, etc, takes its value from a Time Feature, that quantity varies over time. The operation of time-dependent simulation was separated into distinct parts: the Sequence samples time values either sequentially at equal increments or randomly from a uniform distribution (allowing quantities to vary continuously in time), and then each time-dependent quantity is calculated according to its Time Feature. Due to this modular structure, time-dependent simulations, even in the presence of multiple time-dependent quantities, can be efficiently performed in a single simulation with any given time resolution. This approach has been implemented in TOPAS (TOol for PArticle Simulation), designed to make Monte Carlo simulations with Geant4 more accessible to both clinical and research physicists. To demonstrate the method, three clinical situations were simulated: a variable water column used to verify constancy of the Bragg peak of the Crocker Lab eye treatment facility of the University of California, the double-scattering treatment mode of the passive beam scattering system at Massachusetts General Hospital (MGH), where a spinning range modulator wheel accompanied by beam current modulation produces a spread-out Bragg peak, and the scanning mode at MGH, where time-dependent pulse shape, energy distribution and magnetic fields control Bragg peak positions. Results confirm the clinical applicability of the method.


Assuntos
Método de Monte Carlo , Planejamento da Radioterapia Assistida por Computador/métodos , Terapia com Prótons , Fatores de Tempo
19.
Phys Rev Lett ; 106(6): 067005, 2011 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-21405489

RESUMO

Superconductor-ferromagnet (S/F) spin valve effect theories based on the S/F proximity phenomenon assume that the superconducting transition temperature Tc of F1/F2/S or F1/S/F2 trilayers for parallel magnetizations of the F1 and F2 layers (T(c)(P)) are smaller than for the antiparallel orientations (T(c)(AP)). Here, we report for CoOx/Fe1/Cu/Fe2/In multilayers with varying Fe2-layer thickness the sign-changing oscillating behavior of the spin valve effect ΔT(c) = T(c)(AP) - T(c)(P). We observe the full direct effect with T(c)(AP) > T(c)(P) for Fe2-layer thickness d(Fe2) < 1 nm and the full inverse (T(c)(AP) < T(c((P)) effect for d(Fe2) ≥ 1 nm. Interference of Cooper pair wave functions reflected from both surfaces of the Fe2 layer appear as the most probable reason for the observed behavior of ΔT(c).

20.
Nanotechnology ; 21(43): 435501, 2010 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-20876975

RESUMO

We present a novel ultrahigh stability sensor for quantitative magnetic force microscopy (MFM) based on an iron filled carbon nanotube. In contrast to the complex magnetic structure of conventional MFM probes, this sensor constitutes a nanomagnet with defined properties. The long iron nanowire can be regarded as an extended dipole of which only the monopole close to the sample surface is involved in the imaging process. We demonstrate its potential for high resolution imaging. Moreover, we present an easy routine to determine its monopole moment and prove that this calibration, unlike other approaches, is universally applicable. For the first time this enables straightforward quantitative MFM measurements.

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