Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis

Quantum Fluctuations in the Chirped Pendulum

An anharmonic oscillator when driven with a fast, frequency chirped voltage pulse can oscillate with either small or large amplitude depending on whether the drive voltage is below or above a critical value-a well studied classical phenomenon known as autoresonance. Using a 6 GHz superconducting resonator embedded with a Josephson tunnel junction, we have studied for the first time the role of noise in this non-equilibrium system and find that the width of the threshold for capture into autoresonance decreases as the square root of T, and saturates below 150 mK due to zero point motion of the oscillator. This unique scaling results from the non-equilibrium excitation where fluctuations, both quantum and classical, only determine the initial oscillator motion and not its subsequent dynamics. We have investigated this paradigm in an electrical circuit but our findings are applicable to all out of equilibrium nonlinear oscillators.Comment: 5 pages, 4 figure

Cognitive and behavioral predictors of light therapy use

Objective: Although light therapy is effective in the treatment of seasonal affective disorder (SAD) and other mood disorders, only 53-79% of individuals with SAD meet remission criteria after light therapy. Perhaps more importantly, only 12-41% of individuals with SAD continue to use the treatment even after a previous winter of successful treatment. Method: Participants completed surveys regarding (1) social, cognitive, and behavioral variables used to evaluate treatment adherence for other health-related issues, expectations and credibility of light therapy, (2) a depression symptoms scale, and (3) self-reported light therapy use. Results: Individuals age 18 or older responded (n = 40), all reporting having been diagnosed with a mood disorder for which light therapy is indicated. Social support and self-efficacy scores were predictive of light therapy use (p's<.05). Conclusion: The findings suggest that testing social support and self-efficacy in a diagnosed patient population may identify factors related to the decision to use light therapy. Treatments that impact social support and self-efficacy may improve treatment response to light therapy in SAD. © 2012 Roecklein et al

Counting and effective rigidity in algebra and geometry

The purpose of this article is to produce effective versions of some rigidity results in algebra and geometry. On the geometric side, we focus on the spectrum of primitive geodesic lengths (resp., complex lengths) for arithmetic hyperbolic 2-manifolds (resp., 3-manifolds). By work of Reid, this spectrum determines the commensurability class of the 2-manifold (resp., 3-manifold). We establish effective versions of these rigidity results by ensuring that, for two incommensurable arithmetic manifolds of bounded volume, the length sets (resp., the complex length sets) must disagree for a length that can be explicitly bounded as a function of volume. We also prove an effective version of a similar rigidity result established by the second author with Reid on a surface analog of the length spectrum for hyperbolic 3-manifolds. These effective results have corresponding algebraic analogs involving maximal subfields and quaternion subalgebras of quaternion algebras. To prove these effective rigidity results, we establish results on the asymptotic behavior of certain algebraic and geometric counting functions which are of independent interest.Comment: v.2, 39 pages. To appear in Invent. Mat

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Mellin Amplitudes for Dual Conformal Integrals

Motivated by recent work on the utility of Mellin space for representing conformal correlators in $AdS$/CFT, we study its suitability for representing dual conformal integrals of the type which appear in perturbative scattering amplitudes in super-Yang-Mills theory. We discuss Feynman-like rules for writing Mellin amplitudes for a large class of integrals in any dimension, and find explicit representations for several familiar toy integrals. However we show that the power of Mellin space is that it provides simple representations even for fully massive integrals, which except for the single case of the 4-mass box have not yet been computed by any available technology. Mellin space is also useful for exhibiting differential relations between various multi-loop integrals, and we show that certain higher-loop integrals may be written as integral operators acting on the fully massive scalar $n$-gon in $n$ dimensions, whose Mellin amplitude is exactly 1. Our chief example is a very simple formula expressing the 6-mass double box as a single integral of the 6-mass scalar hexagon in 6 dimensions.Comment: 29+7 page

Financial crises and the attainment of the SDGs: an adjusted multidimensional poverty approach

This paper analyses the impact of financial crises on the Sustainable Development Goal of eradicating poverty. To do so, we develop an adjusted Multidimensional Poverty Framework (MPF) that includes 15 indicators that span across key poverty aspects related to income, basic needs, health, education and the environment. We then use an econometric model that allows us to examine the impact of financial crises on these indicators in 150 countries over the period 1980–2015. Our analysis produces new estimates on the impact of financial crises on poverty’s multiple social, economic and environmental aspects and equally important captures dynamic linkages between these aspects. Thus, we offer a better understanding of the potential impact of current debt dynamics on Multidimensional Poverty and demonstrate the need to move beyond the boundaries of SDG1, if we are to meet the target of eradicating poverty. Our results indicate that the current financial distress experienced by many low-income countries may reverse the progress that has been made hitherto in reducing poverty. We find that financial crises are associated with an approximately 10% increase of extreme poor in low-income countries. The impact is even stronger in some other poverty aspects. For instance, crises are associated with an average decrease of government spending in education by 17.72% in low-income countries. The dynamic linkages between most of the Multidimensional Poverty indicators, warn of a negative domino effect on a number of SDGs related to poverty, if there is a financial crisis shock. To pre-empt such a domino effect, the specific SDG target 17.4 on attaining long-term debt sustainability through coordinated policies plays a key role and requires urgent attention by the international community

Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems

Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Intravitreally injected anti-VEGF antibody reduces brown fat in neonatal mice

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondriarelated genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. Copyright