Universal fluctuations in growth dynamics of economic systems

The growth of business firms is an example of a system of complex interacting units that resembles complex interacting systems in nature such as earthquakes. Remarkably, work in econophysics has provided evidence that the statistical properties of the growth of business firms follow the same sorts of power laws that characterize physical systems near their critical points. Given how economies change over time, whether these statistical properties are persistent, robust, and universal like those of physical systems remains an open question. Here, we show that the scaling properties of firm growth previously demonstrated for publicly-traded U.S. manufacturing firms from 1974 to 1993 apply to the same sorts of firms from 1993 to 2015, to firms in other broad sectors (such as materials), and to firms in new sectors (such as Internet services). We measure virtually the same scaling exponent for manufacturing for the 1993 to 2015 period as for the 1974 to 1993 period and virtually the same scaling exponent for other sectors as for manufacturing. Furthermore, we show that fluctuations of the growth rate for new industries self-organize into a power law over relatively short time scales.Comment: 15 pages, 7 figure

TP63 is implicated in apoptotic dysregulation in melanoma

PhDCutaneous melanoma is an aggressive malignancy accounting for 4% of skin cancers but 80% of all skin-cancer related deaths. Its incidence is rapidly rising and advanced disease is notoriously treatment-resistant. The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterised. Mutations in TP53 occur infrequently and are not critical for tumour development, yet the TP53 apoptotic pathway is abrogated; this may alternatively result from TP53 pathway defects or from alterations in other members of the TP53 family, including the TP53 homologue, TP63. The hypothesis of this thesis was that TP63 has an anti-apoptotic role in melanoma and is responsible for mediating chemoresistance. The primary aims were to investigate the biological role of TP63 in melanoma, to explore regulation of p63 expression and to understand its role in apoptosis and dysregulation of the TP53 apoptotic pathway in melanoma. Although p63 was not expressed in primary melanocytes, upregulation of both p63 mRNA and protein was observed in melanoma cell lines and tissue samples. This is the first report of significant p63 expression in this lineage. Furthermore, aberrant cytoplasmic p63 expression significantly correlated with poor overall outcome in melanoma patients. Multiple possible mechanisms were demonstrated to regulate TP63 expression in melanoma, including epigenetic modulation, microRNA regulation of gene transcription and proteosome-dependent stability of p63 protein. In response to genotoxic stress, endogenous p63 isoforms were stabilised in both nuclear and mitochondrial subcellular compartments. Translocation of p63 to the mitochondria occurred through a co-dependent process with p53 but accumulation of wt-p53 in the nucleus was inhibited by p63. Using RNAi technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance in melanoma. In addition, the truncated variant, ΔNp63, was enriched in a subset of melanomas expressing CD133, pointing to an anti-apoptotic role for p63 in putative cancer stem cells in this aggressive tumour. Taken together, these data suggest that in melanoma, p63 is an oncogene which contributes to dysregulation of wt-p53 function and has an important role in mediating chemoresistance. Ultimately, these observations may provide the rationale for novel approaches aimed at sensitising advanced melanoma to chemotherapeutic agents

Stochastic Stability of Discrete-time Phase-coupled Oscillators over Uncertain and Random Networks

This paper studies stochastic stability of a class of discrete-time phase-coupled oscillators. We introduce the two new notions of stochastic and ultimate stochastic phase-cohesiveness using the concepts of Harris and positive Harris recurrent Markov chains. Stochastic phase-cohesiveness of oscillators in two types of networks are studied. First, oscillators in a network with an underlying connected topology subject to both multiplicative and additive stochastic uncertainties are considered. Second, we study a special case of the former problem by assuming that the multiplicative uncertainties are governed by the Bernoulli process representing the well known Erd{\H o}s R\'enyi network

Applicability of the National Comprehensive Cancer Network/Multinational Association of Supportive Care in Cancer Guidelines for Prevention and Management of Chemotherapy-Induced Nausea and Vomiting in Southeast Asia: A Consensus Statement.

A meeting of regional experts was convened in Manila, Philippines, to develop a resource-stratified chemotherapy-induced nausea and vomiting (CINV) management guideline. In patients treated with highly emetogenic chemotherapy in general clinical settings, triple therapy with a serotonin (5-hydroxytryptamine-3 [5-HT3]) antagonist (preferably palonosetron), dexamethasone, and aprepitant is recommended for acute CINV prevention. In resource-restricted settings, triple therapy is still recommended, although a 5-HT3 antagonist other than palonosetron may be used. In both general and resource-restricted settings, dual therapy with dexamethasone (days 2 to 4) and aprepitant (days 2 to 3) is recommended to prevent delayed CINV. In patients treated with moderately emetogenic chemotherapy, dual therapy with a 5-HT3 antagonist, preferably palonosetron, and dexamethasone is recommended for acute CINV prevention in general settings; any 5-HT3 antagonist can be combined with dexamethasone in resource-restricted environments. In general settings, for the prevention of delayed CINV associated with moderately emetogenic chemotherapy, corticosteroid monotherapy on days 2 and 3 is recommended. If aprepitant is used on day 1, it should be continued on days 2 and 3. Prevention of delayed CINV with corticosteroids is preferred in resource-restricted settings. The expert panel also developed CINV management guidelines for anthracycline plus cyclophosphamide combination schedules, multiday cisplatin, and chemotherapy with low or minimal emetogenic potential, and its recommendations are detailed in this review. Overall, these regional guidelines provide definitive guidance for CINV management in general and resource-restricted settings. These consensus recommendations are anticipated to contribute to collaborative efforts to improve CINV management in Southeast Asia

Can genetic engineering for the poor pay off? : an ex-ante evaluation of Golden Rice in India

Genetic engineering (GE) in agriculture is a controversial topic in science and society at large. While some oppose genetically modified crops as proxy of an agricultural system they consider unsustainable and inequitable, the question remains whether GE can benefit the poor within the existing system and what needs to be done to deliver these benefits? Golden Rice has been genetically engineered to produce provitamin A. The technology is still in the testing phase, but, once released, it is expected to address one consequence of poverty ? vitamin A deficiency (VAD) ? and its health implications. Current interventions to combat VAD rely mainly on pharmaceutical supplementation, which is costly in the long run and only partially successful. We develop a methodology for ex-ante evaluation, taking into account the whole sequence of effects between the cultivation of the crop and its ultimate health impacts. In doing so we build on a comprehensive, nationally representative data set of household food consumption in India. Using a refined disability-adjusted life year (DALY) framework and detailed health data, this study shows for India that under optimistic assumptions this country?s annual burden of VAD of 2.3 million DALYs lost can be reduced by 59.4% hence 1.4 million healthy life years could be saved each year if Golden Rice would be consumed widely. In a low impact scenario, where Golden Rice is consumed less frequently and produces less provitamin A, the burden of VAD could be reduced by 8.8%. However, in both scenarios the cost per DALY saved through Golden Rice (US$ 3.06-19.40) is lower than the cost of current supplementation efforts, and it outperforms international cost-effectiveness thresholds. Golden Rice should therefore be considered seriously as a complementary intervention to fight VAD in rice-eating populations in the medium term

High-Order Numerical Method for 1D Non-local Diffusive Equation

In this paper we present a non-local numerical scheme based on the Local Discontinuous Galerkin method for a non-local diffusive partial differential equation with application to traffic flow. In this model, the velocity is determined by both the average of the traffic density as well as the changes in the traffic density at a neighborhood of each point. We discuss nonphysical behaviors that can arise when including diffusion, and our measures to prevent them in our model. The numerical results suggest that this is an accurate method for solving this type of equation and that the model can capture desired traffic flow behavior. We show that computation of the non-local convolution results in $\mathcal{O}(n^2)$ complexity, but the increased computation time can be mitigated with high-order schemes like the one proposed.Comment: 17 pages and 8 figure