Single to double mill small noise transition via semi-Lagrangian finite volume methods

We show that double mills are more stable than single mills under stochastic perturbations in swarming dynamic models with basic attraction-repulsion mechanisms. In order to analyse this fact accurately, we will present a numerical technique for solving kinetic mean field equations for swarming dynamics. Numerical solutions of these equations for different sets of parameters will be presented and compared to microscopic and macroscopic results. As a consequence, we numerically observe a phase transition diagram in terms of the stochastic noise going from single to double mill for small stochasticity fading gradually to disordered states when the noise strength gets larger. This bifurcation diagram at the inhomogeneous kinetic level is shown by carefully computing the distribution function in velocity space

Quadratic optimal functional quantization of stochastic processes and numerical applications

In this paper, we present an overview of the recent developments of functional quantization of stochastic processes, with an emphasis on the quadratic case. Functional quantization is a way to approximate a process, viewed as a Hilbert-valued random variable, using a nearest neighbour projection on a finite codebook. A special emphasis is made on the computational aspects and the numerical applications, in particular the pricing of some path-dependent European options.Comment: 41 page

Global burden of human brucellosis : a systematic review of disease frequency

BACKGROUND: This report presents a systematic review of scientific literature published between 1990-2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis.METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden.CONCLUSIONS: High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understand of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources

The unique ethical challenges of conducting research in the rehabilitation medicine population

BACKGROUND: The broad topic of research ethics is one which has been relatively well-investigated and discussed. Unique ethical issues have been identified for such populations as pediatrics, where the issues of consent and assent have received much attention, and obstetrics, with concerns such as the potential for research to cause harm to the fetus. However, little has been written about ethical concerns which are relatively unique to the population of patients seen by the practitioner of rehabilitation medicine. DISCUSSION: This paper reviews unique ethical concerns in conducting research in this population, including decision-making capacity, communication, the potential for subject overuse, the timing of recruitment, hope for a cure and therapeutic misconception and the nature of the health care provider-research subject relationship. SUMMARY: Researchers in the area of rehabilitation medicine should be aware of some of the unique ethical challenges posed by this patient population and should take steps to address any potential concerns in order to optimize subject safety and ensure that studies meet current ethical guidelines and standards

Clinical and Economic Value of a Biosimilar Portfolio to Stakeholders: An Integrative Literature Review

Grace E Fox,1 Mark Bernauer,1 Jennifer M Stephens,1 Bianca Jackson,1 Joshua A Roth,2 Ahmed Shelbaya2,3 1Strategic Market Access, OPEN Health, Bethesda, MD, USA; 2Global Access and Value, Pfizer Inc., New York, NY, USA; 3Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USACorrespondence: Mark Bernauer, Strategic Market Access, OPEN Health, Bethesda, MD, USA, Tel +1 240 821-1292, Email [email protected]: While the value of individual biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings between biosimilars and originators. Stakeholders may consider the value of a manufacturer’s biosimilar portfolio, especially when negotiating portfolio-based contracts or other rebate programs. However, little is known about what other types of value, in addition to financial benefits, decision-makers perceive regarding a manufacturer with a biosimilar portfolio compared to those without one. The objective of this integrative literature review was to describe a conceptual framework consisting of themes that may help define the value of a biosimilar portfolio.Methods: An integrative literature review was conducted using Excerpta Medica Database (Embase) and Medical Literature Analysis and Retrieval System Online (MEDLINE). Grey literature searches of search engines, journals not indexed in Embase or MEDLINE, healthcare payers, health technology assessment bodies, value frameworks, and non-pharmaceutical industry analogs were also conducted. Eligible studies reported on the value of a biosimilar portfolio in decision-making by stakeholders. Apart from the literature, insights were gained from clinical experience and observation.Results: No studies investigating biosimilar portfolio value were identified; however, several themes were identified that may help define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; and transaction costs. Several non-pharmaceutical industry analogs were identified: Product line length and single-supplier versus multiple-supplier procurement. Several themes were identified through other sources: Science credibility and research. Based on these themes, we developed a conceptual framework for biosimilar portfolio value.Conclusion: To our knowledge, this is the first study to systematically assess and create a framework for biosimilar portfolio value. The conceptual framework described here could be tested to quantify the clinical and economic value associated with a biosimilar portfolio.Plain Language Summary: Though the value of single biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings incurred between biosimilars and originators.We identified seven themes that may help to define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; transaction costs; science credibility; and research.These themes may be integrated into a conceptual framework that may form a basis to help quantify the clinical and economic benefit of a biosimilar portfolio to stakeholders.Keywords: biosimilar, portfolio, value, analo

Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care

Three applications of path integrals: equilibrium and kinetic isotope effects, and the temperature dependence of the rate constant of the [1,5] sigmatropic hydrogen shift in (Z)-1,3-pentadiene

Recent experiments have confirmed the importance of nuclear quantum effects even in large biomolecules at physiological temperature. Here we describe how the path integral formalism can be used to describe rigorously the nuclear quantum effects on equilibrium and kinetic properties of molecules. Specifically, we explain how path integrals can be employed to evaluate the equilibrium (EIE) and kinetic (KIE) isotope effects, and the temperature dependence of the rate constant. The methodology is applied to the [1,5] sigmatropic hydrogen shift in pentadiene. Both the KIE and the temperature dependence of the rate constant confirm the importance of tunneling and other nuclear quantum effects as well as of the anharmonicity of the potential energy surface. Moreover, previous results on the KIE were improved by using a combination of a high level electronic structure calculation within the harmonic approximation with a path integral anharmonicity correction using a lower level method.Comment: 9 pages, 4 figure

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

The Subak in Diaspora: Balinese Farmers and the Subak in South Sulawesi

The subak has a long history as an irrigators’ institution on Bali. It has also spread across Indonesia along with Balinese farmers who were resettled by colonial and post-colonial governments or who have migrated spontaneously since colonial times. While subaks have been much researched in Bali itself, little is known about subaks outside Bali. Luwu District in South Sulawesi is one of the areas where thousands of Balinese families settled in the last four decades. Based on research in this transmigration area, this paper analyzes the emergence and development of the subak in relation to the development of irrigation infrastructure of a state-built irrigation system. A comparison between two Balinese settlements in the same system shows that differences in infrastructural and managerial conditions and arrangements between parts of the irrigation system were major determinants of the institutional space allowed for the subak and ways in which the subaks developed