Implicit Lagrange-Routh Equations and Dirac Reduction

In this paper, we make a generalization of Routh's reduction method for Lagrangian systems with symmetry to the case where not any regularity condition is imposed on the Lagrangian. First, we show how implicit Lagrange-Routh equations can be obtained from the Hamilton-Pontryagin principle, by making use of an anholonomic frame, and how these equations can be reduced. To do this, we keep the momentum constraint implicit throughout and we make use of a Routhian function defined on a certain submanifold of the Pontryagin bundle. Then, we show how the reduced implicit Lagrange-Routh equations can be described in the context of dynamical systems associated to Dirac structures, in which we fully utilize a symmetry reduction procedure for implicit Hamiltonian systems with symmetry.Comment: 21 pages, to appear in J. Geom. Phy

Prognostic impact of peritumoral lymphocyte infiltration in soft tissue sarcomas

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to clarify the prognostic significance of peritumoral lymphocyte infiltration in the capsule of soft tissue sarcomas (STS). Multiple observations in preclinical and clinical studies have shown that the immune system has a role in controlling tumor growth and progression. Prognostic markers in potentially curable STS should guide therapy after surgical resection. The immune status at the time of resection may be important, but the prognostic significance of peritumoral lymphocytes is unknown.</p> <p>Methods</p> <p>Tissue microarrays from 80 patients with STS were constructed from duplicate cores of tissue from the tumor and the peritumoral capsule. Immunohistochemistry was used to evaluate the CD3+, CD4+, CD8+ and CD20+ lymphocytes in the tumor and the peritumoral capsule.</p> <p>Results</p> <p>In univariate analyses, increasing numbers of CD20+ (<it>P </it>= 0.032) peritumoral lymphocytes were associated with a reduced disease free survival (DSS). In multivariate analyses, a high number of CD20+ peritumoral lymphocytes (<it>P </it>= 0.030) in the capsule was an independent negative prognostic factor for DSS. There were no such associations of lymphocyte infiltration in the tumor.</p> <p>Conclusions</p> <p>A high density of CD20+ peritumoral lymphocytes is an independent negative prognostic indicator for patients with STS. Further research is needed to determine whether CD20 cells in the peritumoral capsule of STS may promote tumor invasion in the surrounding tissue and increase the metastatic potential.</p

Neurobiological correlates of antisociality across adolescence and young adulthood: a multi-sample, multi-method study

Background Antisociality across adolescence and young adulthood puts individuals at high risk of developing a variety of problems. Prior research has linked antisociality to autonomic nervous system and endocrinological functioning. However, there is large heterogeneity in antisocial behaviors, and these neurobiological measures are rarely studied conjointly, limited to small specific studies with narrow age ranges, and yield mixed findings due to the type of behavior examined. Methods We harmonized data from 1489 participants (9-27 years, 67% male), from six heterogeneous samples. In the resulting dataset, we tested relations between distinct dimensions of antisociality and heart rate, pre-ejection period (PEP), respiratory sinus arrhythmia, respiration rate, skin conductance levels, testosterone, basal cortisol, and the cortisol awakening response (CAR), and test the role of age throughout adolescence and young adulthood. Results Three dimensions of antisociality were uncovered: 'callous-unemotional (CU)/manipulative traits', 'intentional aggression/conduct', and 'reactivity/impulsivity/irritability'. Shorter PEPs and higher testosterone were related to CU/manipulative traits, and a higher CAR is related to both CU/manipulative traits and intentional aggression/conduct. These effects were stable across age. Conclusions Across a heterogeneous sample and consistent across development, the CAR may be a valuable measure to link to CU/manipulative traits and intentional aggression, while sympathetic arousal and testosterone are additionally valuable to understand CU/manipulative traits. Together, these findings deepen our understanding of the fundamental mechanisms underlying different components of antisociality. Finally, we illustrate the potential of using current statistical techniques for combining multiple datasets to draw robust conclusions about biobehavioral associations

Neurobiological correlates of antisociality across adolescence and young adulthood: A multi-sample, multi-method study

Background Antisociality across adolescence and young adulthood puts individuals at high risk of developing a variety of problems. Prior research has linked antisociality to autonomic nervous system and endocrinological functioning. However, there is large heterogeneity in antisocial behaviors, and these neurobiological measures are rarely studied conjointly, limited to small specific studies with narrow age ranges, and yield mixed findings due to the type of behavior examined. Methods We harmonized data from 1489 participants (9-27 years, 67% male), from six heterogeneous samples. In the resulting dataset, we tested relations between distinct dimensions of antisociality and heart rate, pre-ejection period (PEP), respiratory sinus arrhythmia, respiration rate, skin conductance levels, testosterone, basal cortisol, and the cortisol awakening response (CAR), and test the role of age throughout adolescence and young adulthood. Results Three dimensions of antisociality were uncovered: 'callous-unemotional (CU)/manipulative traits', 'intentional aggression/conduct', and 'reactivity/impulsivity/irritability'. Shorter PEPs and higher testosterone were related to CU/manipulative traits, and a higher CAR is related to both CU/manipulative traits and intentional aggression/conduct. These effects were stable across age. Conclusions Across a heterogeneous sample and consistent across development, the CAR may be a valuable measure to link to CU/manipulative traits and intentional aggression, while sympathetic arousal and testosterone are additionally valuable to understand CU/manipulative traits. Together, these findings deepen our understanding of the fundamental mechanisms underlying different components of antisociality. Finally, we illustrate the potential of using current statistical techniques for combining multiple datasets to draw robust conclusions about biobehavioral associations

Increased Resection Rates and Survival Among Patients Aged 75 Years and Older with Esophageal Cancer: A Dutch Nationwide Population-Based Study

The incidence of esophageal cancer has grown over the recent decades and 30 % of esophageal cancer patients are now 75 years or older at the time of diagnosis. The aim of this study was to evaluate trends in management and survival of patients aged 75 years or older with esophageal cancer. In the Netherlands cancer registry, we identified all patients aged 75 years or older who were diagnosed with esophageal cancer between 1989 and 2008. Trends in management and survival were analyzed by time period (1989-2001 vs. 2002-2008), TNM stage, and age (75-79, 80-84, and 85+ years). chi(2) testing was used to analyze time trends in treatment, Kaplan-Meier analysis and log-rank testing to estimate survival, and Cox regression model to calculate hazard ratios for death. Some 7,253 patients were included in the study. The surgical resection rate increased over the 1989-2008 period from 8.9 to 12.6 % (p = 0.028), especially among patients aged 75-79 years (44.6 vs. 55.4 %, p < 0.001) and patients with TNM stage I disease (12.7 vs. 22.0 %, p < 0.001). The use of definitive chemoradiotherapy (CRT) also increased (0.19 vs. 2.20 %, p < 0.001). Whereas the use of chemotherapy as a single-modality treatment more than doubled (0.64 vs. 1.54 %, p = 0.004), that of radiot In patients of 75 years or older, surgical treatment and use of definitive CRT have increased between 1989 and 2008. Also, an increase in the use of chemotherapy as a single modality was noted. Overall 5 year survival for all cancer patients was stable but remained poor, while survival of patients who underwent esophagectomy improved significantly in the Netherlands since 1989

CSF biomarker variability in the Alzheimer's Association quality control program

Item does not contain fulltextBACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. METHODS: Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Molndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. RESULTS: A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). CONCLUSIONS: The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians