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Today's state-of-the-art automotive head-up displays (HUD) possess single- or double layer focal planes that limit the observers' eye focus to these planes when crucial information is shown. Other visual 3D cues such as motion parallax also suffer from this limitation. The resulting viewing experience contradicts the natural way of viewing during driving or interaction, when alerts and hints should appear at the correct projection depth where real objects of interest are located. Here we present a real-time holographic HUD with continuous depth that supports the intuitive and natural way of viewing and interacting with virtual environments outside and inside the car. We demonstrate full-color, 3D real-time encoding within a field-of-view of 5∘×3∘.
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Percepção de Profundidade , Holografia , Sinais (Psicologia) , Movimento (Física)RESUMO
BACKGROUND: Patients with depression and comorbid obesity may be more prone to weight modulating and cardiovascular side effects of selected antidepressants (AD). It is important to ascertain whether these AD prescriptions differ by patient weight status. METHODS: Canadian Primary Care Sentinel Surveillance Network (CPCSSN) electronic medical records were used. Participants were adults with depression prescribed an AD in 2000-2016, with weight categories established before the first prescription. Logistic regression and mixed effects models were applied to examine associations between obesity and AD prescribing, adjusted for sex, age, and comorbidities. Machine learning algorithm random forest (RF) was used to evaluate the importance of weight in predicting prescribing patterns. RESULTS: Of 26,571 participants, 72.4% were women, mean age was 38.9 years (standard deviation (SD)=14.2) and mean BMI 27.0 kg/m2 (SD = 6.5); 9.5% had ≥ 1 comorbidity. Patients with obesity, compared to normal weight patients, were more likely to receive bupropion (adjusted odds ratio (aOR) 1.24, 95%CI: 1.09,1.42), fluoxetine (aOR 1.14, 95%CI: 0.97,1.34), and amitriptyline (aOR 1.13, 95%CI: 0.93,1.36), and less likely to receive mirtazapine (aOR 0.55, 95%CI: 0.44,0.68) and escitalopram (aOR 0.88, 95%CI: 0.80, 0.97). RF analysis showed that weight was among the most important predictors of prescribing patterns, equivalent to age and more important than sex. CONCLUSIONS: AD prescribing patterns for patients with obesity appear to be different for selected AD types, including AD known for their weight-modulating and cardiovascular side effects. Longitudinal studies are needed to examine whether these prescribing patterns are associated with significant health outcomes.
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Antidepressivos , Citalopram , Adulto , Antidepressivos/efeitos adversos , Canadá , Feminino , Humanos , Mirtazapina , Obesidade/induzido quimicamente , Obesidade/epidemiologiaRESUMO
PURPOSE: Within the framework of a questionnaire-based health survey in Germany, we examined ambulant health care utilisation among childhood cancer survivors' offspring compared to utilisation among children of the general population. METHODS: In total, 1299 former patients received a questionnaire for every known biological child in two cross-sectional surveys, 2013/14 (n = 393) and 2015/16 (n = 906). For investigation of health care utilisation, questions on frequencies and kind of ambulant medical services were chosen for bivariate and multivariate analyses. Correlations between utilisation and anxiety, diagnosis of the parent, pain or preterm birth of the child and social indicators were conducted. For comparison with the general population, data of 17,640 children and adolescents aged 0 to 17 years were used for matched-pair analysis. These data were available from the KIGGS baseline study on the health of children and adolescents in Germany, conducted by the Robert Koch Institute. RESULTS: Overall, 852 (65.6%) of the contacted 1299 survivors completed 1340 questionnaires on their children's health. Childhood cancer survivors' offspring showed a similar attendance of ambulant primary health care compared to the general population (paediatricians 83.1% vs. 82.1%). However, the majority of specialist physicians was visited significantly more often (e.g. dermatologist 10.5% vs. 6.2%) by childhood cancer survivors' offspring compared to children from the general population. Logistic regression showed that parental diagnosis and anxiety on children's health significantly influenced health care utilisation. CONCLUSIONS: Further improvement of after-care for childhood cancer survivors by including topics on offspring seems necessary. Offspring's paediatricians should implement counselling and providing of information considering the special family anamnesis.
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Sobreviventes de Câncer/estatística & dados numéricos , Inquéritos Epidemiológicos/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Família , Feminino , Alemanha , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Neoplasias/terapia , Pais , Inquéritos e QuestionáriosRESUMO
Quantum scrambling is the dispersal of local information into many-body quantum entanglements and correlations distributed throughout an entire system. This concept accompanies the dynamics of thermalization in closed quantum systems, and has recently emerged as a powerful tool for characterizing chaos in black holes1-4. However, the direct experimental measurement of quantum scrambling is difficult, owing to the exponential complexity of ergodic many-body entangled states. One way to characterize quantum scrambling is to measure an out-of-time-ordered correlation function (OTOC); however, because scrambling leads to their decay, OTOCs do not generally discriminate between quantum scrambling and ordinary decoherence. Here we implement a quantum circuit that provides a positive test for the scrambling features of a given unitary process5,6. This approach conditionally teleports a quantum state through the circuit, providing an unambiguous test for whether scrambling has occurred, while simultaneously measuring an OTOC. We engineer quantum scrambling processes through a tunable three-qubit unitary operation as part of a seven-qubit circuit on an ion trap quantum computer. Measured teleportation fidelities are typically about 80 per cent, and enable us to experimentally bound the scrambling-induced decay of the corresponding OTOC measurement.
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Reactive and neoplastic thymic pathologies are the main considerations in the case of masses in the anterior and middle part of the mediastinum, while neurogenic tumors are predominant in the posterior mediastinum (which are not dealt with here). In neonates and infants, the commonest pathologies in the anterior mediastinum comprise germ cell tumors (mainly teratomas), congenital thymic cysts and true thymic hyperplasia (TTH). In toddlers, teratomas, yolk sac tumors and cysts predominate. In children over 5 years of age, lymphomas are the commonest mass lesions whereas thymomas and thymic carcinomas are rare. In addition, inflammation-linked hyperplasia in myasthenia gravis and rebound thymic hyperplasia after chemotherapy must be considered. Although rare at all ages, sarcomas must be considered in the differential diagnosis from birth onwards and throughout adolescence. Based on the report of a rare case of recurrent TTH, the differential diagnosis of this benign but potentially life-threatening condition is discussed.
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Doenças Linfáticas/diagnóstico , Timo/patologia , Hiperplasia do Timo/diagnóstico , Neoplasias do Timo/diagnóstico , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Doenças Linfáticas/patologia , Masculino , Cisto Mediastínico/diagnóstico , Cisto Mediastínico/patologia , Miastenia Gravis/diagnóstico , Miastenia Gravis/patologia , Sarcoma/diagnóstico , Sarcoma/patologia , Teratoma/diagnóstico , Teratoma/patologia , Timectomia , Timoma/diagnóstico , Timoma/patologia , Hiperplasia do Timo/patologia , Neoplasias do Timo/patologia , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Up to 70% of children with attention-deficit/hyperactivity disorder (ADHD) experience sleep problems. We have demonstrated the efficacy of a brief behavioural intervention for children with ADHD in a large randomised controlled trial (RCT) and now aim to examine whether this intervention is effective in real-life clinical settings when delivered by paediatricians or psychologists. We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: Children aged 5-12â years with ADHD (n=320) are being recruited for this translational cluster RCT through paediatrician practices in Victoria and Queensland, Australia. Children are eligible if they meet criteria for ADHD, have a moderate/severe sleep problem and meet American Academy of Sleep Medicine criteria for either chronic insomnia disorder or delayed sleep-wake phase disorder; or are experiencing sleep-related anxiety. Clinicians are randomly allocated at the level of the paediatrician to either receive the sleep training or not. The behavioural intervention comprises 2 consultations covering sleep hygiene and standardised behavioural strategies. The primary outcome is change in the proportion of children with moderate/severe sleep problems from moderate/severe to no/mild by parent report at 3â months postintervention. Secondary outcomes include a range of child (eg, sleep severity, ADHD symptoms, quality of life, behaviour, working memory, executive functioning, learning, academic achievement) and primary caregiver (mental health, parenting, work attendance) measures. Analyses will address clustering at the level of the paediatrician using linear mixed effect models adjusting for potential a priori confounding variables. ETHICS AND DISSEMINATION: Ethics approval has been granted. Findings will determine whether the benefits of an efficacy trial can be realised more broadly at the population level and will inform the development of clinical guidelines for managing sleep problems in this population. We will seek to publish in leading international paediatric journals, present at major conferences and through established clinician networks. TRIAL REGISTRATION NUMBER: ISRCTN50834814, Pre-results.
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Terapia Comportamental/métodos , Memória de Curto Prazo/fisiologia , Saúde Mental , Qualidade de Vida , Transtornos do Sono-Vigília/terapia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Pré-Escolar , Análise por Conglomerados , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Queensland/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Inquéritos e Questionários , Resultado do Tratamento , Vitória/epidemiologiaRESUMO
Purpose: Childhood cancer survivors fear that previous therapy could not only impair their own but also their children's health. We examined whether health-related behaviour in children of childhood cancer survivors differs from the general population. Methods: Our first nationwide survey wave (2013-2014) surveyed offspring health in 396 German childhood cancer survivors known to have a child of their own. Answers about health behaviour were analysed using descriptive statistics. Data were collected for 418 offspring and 394 could be integrated for matched-pair analyses with data from the German general population (KIGGS, n=17 641). Results: Teeth-cleaning routine, body-mass-index or subjective body image evaluation by parents were no different from children in the general population. Parents who included a cancer survivor smoked less in the presence of their children (p=0.01). During pregnancy, mothers in cancer survivor parent pairs abstained from drinking alcohol more often (p=0.01) and smoked less (p=0.05). While the calculated effect sizes (Phi) were generally low (0.135-0.247), children from cancer survivors played less outdoors than peers did (p=0.01). Boys participated in sports outside a club more often (p=0.05) and watched less TV on weekdays (p=0.01) and girls spent more time on the computer during weekdays than peers did (p=0.01). Conclusions: This study provides the first data for health-related behaviour in cancer survivors' offspring and sheds light on differences to parenting in the general population. Multivariate analyses in a larger study population are needed to relate these differences to fear issues in cancer survivors.
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Sobreviventes de Câncer/psicologia , Saúde da Criança , Filho de Pais com Deficiência/psicologia , Comportamentos Relacionados com a Saúde , Adulto , Imagem Corporal/psicologia , Índice de Massa Corporal , Criança , Exercício Físico/psicologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Higiene Bucal/psicologia , Grupo Associado , Gravidez , Valores de Referência , Abandono do Hábito de Fumar/psicologiaRESUMO
BACKGROUND: The alarming prevalence of heart failure with preserved ejection fraction requires quantification of diastolic dysfunction (DDF). Myocardial diastolic velocity E' implies that age is the most important determinant. We tested the hypothesis that age allows for quantification of DDF and assessment of the structural and metabolic determinants in patients with and without type 2 diabetes (D). METHODS: This prospective, cross-sectional study assessed cardiovascular, metabolic and ultrasound data in 409 consecutive patients (Diabetes Center, Bogenhausen-Munich) between 20 and 90 years without known cardiac disease and either with (n=204) or without D but with common prevalence of cardiovascular risk factors, including a subgroup of healthy individuals (H, n=94). RESULTS: In H, E' related to age as: E'norm=-0.163∗years+19.69 (R(2)=0.77, p<0.0001). According to this 1% reduction by annual physiologic aging, DDF was quantitated as E'-E' norm. Compared to nondiabetics, D patients were older, had greater BMI, lower E', more cardiovascular risk and greater DDF. In nondiabetics, grading of DDF by E-E'norm correlated with grading by filling pressure E/E'. Determinants of DDF by multivariate analysis included pulse wave velocity, diastolic blood pressure and the triglyceride/HDL ratio (a marker of insulin resistance) in nondiabetics and in D the same risk factors in reverse sequence and heart rate. Neither left atrial size nor left ventricular mass had significant impact. CONCLUSIONS: The physiological impact of age on myocardial function consists of a 1% annual reduction in E' and enables precise quantification of diastolic dysfunction thereby unmasking the importance of metabolic risk for DDF.
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Diabetes Mellitus Tipo 2/complicações , Insuficiência Cardíaca Diastólica/fisiopatologia , Resistência à Insulina , Disfunção Ventricular Esquerda/fisiopatologia , Fatores Etários , Comorbidade/tendências , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Saúde Global , Insuficiência Cardíaca Diastólica/diagnóstico , Insuficiência Cardíaca Diastólica/epidemiologia , Humanos , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/epidemiologiaRESUMO
Biased effect estimates induced by unconsidered confounding variables are a known problem in observational studies. Selection bias, resulting from non-random sampling of study participants, is widely recognised as a problem in case-control and cross-sectional studies. In contrast, possible bias in randomised controlled trials (RCTs) is mostly ignored. This paper illustrates, by applying directed acyclic graphs (DAGs), possible bias in the effect estimates of first-line therapy, caused by subsequent changes in therapy (time-dependent confounding). Possible selection bias, induced by not only random loss to follow-up, will be explained as well using DAGs. Underlying assumptions of standard methods usually used to analyse RCTs (like intention-to-treat, per-protocol) are shown and it is explained why effect estimates may be biased in RCTs, if only these conventional methods are used. Adequate statistical methods (causal inference models as marginal structural models and structural nested models) exist. Higher documentary efforts, however, are necessary, because any changes in medication, loss to follow-up as well as reasons for such changes need to be documented in detail as required by these advanced statistical methods. Nevertheless, causal inference models should become standard along side the currently applied standard methods, especially in studies with high non-compliance due to changes in therapy and substantial loss to follow-up. Possible bias cannot be excluded if similar results are obtained from both methods. However, study results should be interpreted with caution if they differ between both approaches.
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Terapia Combinada/estatística & dados numéricos , Fatores de Confusão Epidemiológicos , Interpretação Estatística de Dados , Modelos Estatísticos , Avaliação de Resultados em Cuidados de Saúde/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Simulação por Computador , Humanos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de TempoRESUMO
BACKGROUND: Facing the demographic change, cardiovascular risk factors have been assessed within an occupational checkup to establish health programs. PATIENTS AND METHODS: From 2006 to 2007, anthropometric and blood parameters of 27 359 employees of a large company of the German automobile industry were collected aiming to determine the prevalence of metabolic syndrome (by NCEP ATP III) and its risk factors. Data from 3048 employees (fasting state) were analyzed (age: ∅ 39,4 ± 10,3 years, 81.4% males). RESULTS: The most common risk factors were hypertension ≥ 130/85 mmHg (men [m]: 74,4%, 95%-confidence interval [CI] 73-76%, women [w]: 47,1%, 95%-CI 43-51%), elevated triglycerides (≥ 150 mg/dl; m: 32,8%, 95%-CI 31-35%, w: 13,8%, 95%-CI 11-17%) and waist-circumferences (> 102 cm for men: 15,1%, 95%-CI 14-17%;â > 88 cm for women: 16,9%, 95%-CI 14-20%). The prevalence of metabolic syndrome (≥ 3 risk factors) was 11,7% (95%-CI 12-15%; m: 12,7%, 95%-CI 11-14%, w: 7,4%, 95%-CI 6-10%) increasing with physical inactivity and rising age up to 20%. The prevalence of hypertension in young (< 20 years) and elder men (≥ 50 years) was similarly high (79,1%, 95%-CI 70-86% vs. 79,9%, 95%-CI 75-82%). CONCLUSION: The prevalence of metabolic syndrome in this sample is rather low, but 75% of the men and nearly 50% of the women had hypertension. Health programs should focus on this risk factor in particular.
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Síndrome Metabólica/epidemiologia , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Feminino , Alemanha , Comportamentos Relacionados com a Saúde , Humanos , Estilo de Vida , Masculino , Programas de Rastreamento , Síndrome Metabólica/etiologia , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Serviços de Saúde do Trabalhador , Fatores de RiscoRESUMO
PURPOSE: Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity METHODS: A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. RESULTS: Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed bone infiltration in two additional patients (7 %), who both showed discrete cortical bone erosion not visible by MSCT or MRI. There were no false-positive or false-negative findings on SPECT/CT. The quality criteria for detecting bone involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 % confidence interval limit 80 %), specificity 100 % (75 %), positive predictive value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the retrospective evaluation SPECT showed results similar to SPECT/CT. CONCLUSION: Hybrid SPECT/CT has a high specificity as it can provide additional information about the existence and local extent of malignant bone infiltration of the mandible. Although the sensitivity of conventional SPECT is similar to that of SPECT/CT, the latter provides a much better delineation of the local tumour-bone contact area. Based on this information, surgical intervention of the rim versus partial resection can be planned and performed more precisely. Patient outcome can be improved by avoiding undertreatment and unnecessary or overextended bone resections.
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Osso e Ossos/cirurgia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Imagem Multimodal , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Radiografia Panorâmica , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
PURPOSE: The purpose of this study was to report on the first experiences with freehand single-photon emission-computed tomography (freehand SPECT) in sentinel lymph node biopsy (SLNB) in patients with malignant melanoma. Freehand SPECT is a novel imaging modality combining gamma probes, surgical navigation systems, and emission tomography algorithms, designed to overcome some of the limitations of conventional gamma probes. METHODS: In this study 20 patients with malignant melanoma underwent conventional planar scintigraphy prior to surgery. In the operating room, the number and location of separable SLNs were detected first by a pre-incisional scan with freehand SPECT to render a 3D-image of the target site and afterwards by a scan with a conventional gamma probe. After SLNB another scan was performed to document the removal of all targeted SLNs. RESULTS: Planar scintigraphy identified 40 SLNs in 26 nodal basins. Pre-incisional freehand SPECT mapped 38 of these nodes as well as one additional node in one patient (95.0% node based sensitivity). The results of freehand SPECT were identical to those of planar scintigraphy in 25 basins, while it missed one basin (96.2% basin based sensitivity). In comparison, the gamma probe failed to detect 7 nodes in 4 basins (82.5% node based sensitivity and 84.6% basin based sensitivity). After resection freehand SPECT detected 9 remaining radioactive spots, two of whichwere resected as they matched the position of SLNs detected on preoperative planar scintigraphy. CONCLUSIONS: Freehand SPECT provides a real-time, intraoperative 3D-image of the radioactive labelled SLNs, facilitating their detection and resection.
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Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Salas Cirúrgicas , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: The goal of the present work was to localize and quantify the actual delivered dose to the cervical spinal cord (SC) during head and neck cancer (H&N) treatment. MATERIALS AND METHODS: A total of 20 H&N patients treated with bilateral nodal irradiation with helical tomotherapy (HT) were analyzed. Daily MVCTs were performed for image guidance. On every second MVCT, the SC was recontoured and the delivered dose for the given treatment fraction (12 fractions per patient) was recalculated. The magnitude and localization (CT slice, spinal cord quadrant) of the Dmax to the SC on the planning CT (PLAN-Dmax) and of the actual delivered Dmax (a-Dmax) were analyzed. RESULTS: A systematic deviation from the PLAN-Dmax was observed in 15 out of 20 patients. Large interpatient variability of the a-Dmax in the spinal cord was noted (4.5±4%). Intrapatient variability in a-Dmax was, generally, minimal (1.8±2.7%). Throughout the treatment course, the higher dose was located in the same CT slices and in the same quadrants (anterior right and anterior left) for the same patient. CONCLUSION: Exact localization and quantification of the change of the a-Dmax can be made for most patients by recalculating the dose on the daily IGRT-MVCTs. This could be helpful in assessing whether replanning is necessary in patients with doses close to the known tolerance doses of the spinal cord.
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Neoplasias de Cabeça e Pescoço/radioterapia , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia Guiada por Imagem/métodos , Medula Espinal/efeitos da radiação , Humanos , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Genomic rearrangements at the fragile site FRA1E may disrupt the dihydropyrimidine dehydrogenase gene (DPYD) which is involved in 5-fluorouracil (5-FU) catabolism. In triple-negative breast cancer (TNBC), a subtype of breast cancer frequently deficient in DNA repair, we have investigated the susceptibility to acquire copy number variations (CNVs) in DPYD and evaluated their impact on standard adjuvant treatment. METHODS: DPYD CNVs were analysed in 106 TNBC tumour specimens using multiplex ligation-dependent probe amplification (MLPA) analysis. Dihydropyrimidine dehydrogenase (DPD) expression was determined by immunohistochemistry in 146 tumour tissues. RESULTS: In TNBC, we detected 43 (41%) tumour specimens with genomic deletions and/or duplications within DPYD which were associated with higher histological grade (P=0.006) and with rearrangements in the DNA repair gene BRCA1 (P=0.007). Immunohistochemical analysis revealed low, moderate and high DPD expression in 64%, 29% and 7% of all TNBCs, and in 40%, 53% and 7% of TNBCs with DPYD CNVs, respectively. Irrespective of DPD protein levels, the presence of CNVs was significantly related to longer time to progression in patients who had received 5-FU- and/or anthracycline-based polychemotherapy (hazard ratio=0.26 (95% CI: 0.07-0.91), log-rank P=0.023; adjusted for tumour stage: P=0.037). CONCLUSION: Genomic rearrangements in DPYD, rather than aberrant DPD protein levels, reflect a distinct tumour profile associated with prolonged time to progression upon first-line chemotherapy in TNBC.
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Variações do Número de Cópias de DNA , Di-Hidrouracila Desidrogenase (NADP)/genética , Recidiva Local de Neoplasia/genética , Neoplasias de Mama Triplo Negativas/genética , Antimetabólitos Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Sítios Frágeis do Cromossomo/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Fluoruracila/uso terapêutico , Deleção de Genes , Duplicação Gênica/efeitos dos fármacos , Duplicação Gênica/genética , Rearranjo Gênico/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Radiografia , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/enzimologiaRESUMO
We prepare a superposition of two motional states by addressing lithium atoms immersed in a Bose-Einstein condensate of sodium with a species-selective potential. The evolution of the superposition state is characterized by the populations of the constituent states as well as their coherence. The latter we extract employing a novel scheme analogous to the spin-echo technique. Comparing the results directly to measurements on freely evolving fermions allows us to isolate the decoherence effects induced by the bath. In our system, the decoherence time is close to the maximal possible value since the decoherence is dominated by population relaxation processes. The measured data are in good agreement with a theoretical model based on Fermi's golden rule.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Mutação/genética , Qualidade de Vida , Feminino , Humanos , MasculinoRESUMO
PURPOSE: To report on chronic adverse events (CAE) and quality of life (QOL) after radiochemotherapy (RCT) in patients with anal cancer (AC). PATIENTS AND METHODS: Of 83 patients who had received RCT at our department between 1988 and 2011, 51 accepted the invitation to participate in this QOL study. CAE were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 and QOL was assessed with the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire. RESULTS: CAE could be evaluated in 49 patients. There was a tendency toward a higher rate of grade 3 CAE in female patients, i.e. 18 out of 37 (49 %) vs. 2 out of 12 (17 %) male patients (p = 0.089). The most common grade 3 CAE were dyspareunia and vaginal symptoms (itching, burning and dryness) in 35 and 22 % of female patients, respectively, followed by stool incontinence in 13 % of all patients (6 out of 49). Both FACT-C and CAE information were available for 42 patients, allowing evaluation of the impact of CAE on QOL. The median total FACT-C score was 110 (40-132) out of a possible maximum of 136. The absence of grade 3 CAE (115 vs. 94, p = 0.001); an interval of ≥ 67 months after the end of the treatment (111 vs. 107, p = 0.010), no stool incontinence vs. grade 3 stool incontinence (111 vs. 74, p = 0.009), higher education (114 vs. 107, p = 0.013) and no dyspareunia vs. grade 3 dyspareunia (116 vs. 93, p = 0.012) were significantly associated with a higher median FACT-C score. CONCLUSION: The majority of AC patients treated with RCT have acceptable overall QOL scores, which are comparable to those of the normal population. Patients with grade 3 CAE-particularly dyspareunia and fecal incontinence-have a poorer QOL compared to patients without CAE. In order to improve long-term QOL, future strategies might aim at a reduction in dose to the genitalia and more intensive patient support measures.
Assuntos
Neoplasias do Ânus/terapia , Quimiorradioterapia/efeitos adversos , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Quimiorradioterapia/métodos , Quimiorradioterapia/psicologia , Dispareunia/etiologia , Incontinência Fecal/etiologia , Feminino , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Reto/efeitos da radiação , Sistema Urogenital/efeitos da radiação , Vagina/efeitos da radiaçãoRESUMO
BACKGROUND: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after neoadjuvant docetaxel/platin/fluoropyrimidine-based chemotherapy. PATIENTS AND METHODS: Patients received at least one cycle of chemotherapy for potentially operable disease. Pretreatment clinicopathologic factors and pCR were investigated. Disease-free survival (DFS), overall survival (OS) and tumor-related death were correlated with pCR. RESULTS: One hundred twenty patients were included in this analysis. Eighteen patients (15%) achieved a pCR. Tumor localization in the EGJ was identified as the only significant predictor of pCR (P = 0.019). Median follow-up was 41.1 months. Median DFS and OS for all patients were 24.1 and 48.6 months, respectively. Median DFS for patients with a pCR was not reached versus 22.1 months non-pCR patients (hazard ratio, HR 0.38; 3-year DFS: 71.8% and 37.7%, respectively, P = 0.018). While OS was not significantly different, the risk for tumor-related death was significantly lower for pCR patients compared with non-pCR patients (3-year cumulative incidences of 6.4% and 45.4%, respectively, P = 0.009). CONCLUSION: A pCR following preoperative docetaxel/platin/fluoropyrimidine indicates favorable outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ is associated with a higher pCR rate.
Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Taxoides/uso terapêutico , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Docetaxel , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/efeitos dos fármacos , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Indução de Remissão , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Sobrevida , Taxa de Sobrevida , Complexo Vitamínico B/uso terapêuticoRESUMO
The involvement of the neuropeptides oxytocin (OXT) and vasopressin (AVP) in human socio-emotional behaviours is attracting increasing attention. There is ample evidence for elevated plasma levels upon a wide variety of social and emotional stimuli and scenarios, ranging from romantic love via marital distress up to psychopathology, with cause versus consequence being largely unclear. The present study examined whether plasma levels of both OXT and AVP are reflective of central neuropeptide levels, as assumed to impact upon socio-emotional behaviours. Concomitant plasma and cerebrospinal fluid (CSF) samples were taken from 41 non-neurological and nonpsychiatric patients under basal conditions. Although OXT and AVP levels in the CSF exceeded those in plasma, there was no correlation between both compartments, clearly suggesting that plasma OXT and AVP do not predict central neuropeptide concentrations. Thus, the validity of plasma OXT and AVP as potential biomarkers of human behaviour needs further clarification.