An Integro-Differential Equation of the Fractional Form: Cauchy Problem and Solution

Producción CientíficaWe solve the Cauchy problem defined by the fractional partial differential equation [∂tt − κD]u = 0, with D the pseudo-differential Riesz operator of first order, and certain initial conditions. The solution of the Cauchy problem resulting from the substitution of the Gaussian pulse u(x, 0) by the Dirac delta distribution ϕ(x) = μδ(x) is obtained as corollary.MINECO grant MTM2014-57129-C2-1-P

Delivering New Malaria Drugs through Grassroots Private Sector

Objective: To demonstrate that micro-franchising system is an effective way of improving access to effective health care such as the introduction of first line antimalarias in populations living in underserved rural areas in Kenya.Design: A descriptive study.Setting: Child and family wellness (CFW) micro-franchised nurse run clinics in Kenya.Results: In 2007, 39.3% of RDTs carried out were positive for malaria. All malaria positive (RDTs and microscopy) patients received artemether lumefantrine (AL) according to their weight in accordance with the Government approved treatment guidelines. During the same period a total of 3,248 community members were reached with malaria information, however, community expectations took longer to change as patients demanded AL even when the malaria diagnosis was negative. Initially, this led to the dispensing of other antimalarials to patients with malaria like symptoms even with a negative test. This demand decreased with more community education on the importance of the tests. Engaging the private sector though with challenges proved feasible and appropriate in accessing malaria treatment based on clinical diagnosis supported by RDTs to confirm the diagnosis instead of presumptive treatment based on fever. This led to a reduction of antimalarial prescriptions by more than 50%, implying better patient care, rational drug use as well as cost savings on malaria treatment. Conclusion: A micro-franchising system is an effective and sustainable way of improving access to effective health care by populations living in underserved rural areas ofAfrica. With appropriate supportive training and supervision, the system can adapt to changes in treatment guidelines and to new regimens

Cosmology = topology/geometry: mathematical evidence for the Holographic Principle

In August 2015 NORDITA (Nordic Institute for Theoretical Physics) hosted a conference where Hawking strongly supported the conjectured relationship between string theory and quantum fields that was initiated with the holographic principle some 20 years ago by ’t Hooft, Maldacena, Susskind and Witten. We bring together results of several papers showing how mathematics can come to the party: the fundamentals of flat (even higher-dimensional) space can be derived very simply from topological properties on a surface. Specifically, Desargues, Pappus or other configurations do not have to be assumed a priori or as self-evident (a fundamental weakness of Hilbert’s work in 1899) to develop the foundations of geometry. Are black holes places where non-commutative (quantum) behaviour reigns while Euclidean (flat) space is where commutativity holds sway? So, we cannot hope to look inside a black hole unless we know how “deformable” topology is related to “flat” geometry

Flocculation on a chip: a novel screening approach to determine floc growth rates and select flocculating agents

Flocculation is a key purification step in cell-based processes for the food and pharmaceutical industry where the removal of cells and cellular debris is aided by adding flocculating agents. However, finding the best suited flocculating agent and optimal conditions to achieve rapid and effective flocculation is a nontrivial task. In conventional analytical systems, turbulent mixing creates a dynamic equilibrium between floc growth and breakage, constraining the determination of floc formation rates. Furthermore, these systems typically rely on end-point measurements only. We have successfully developed for the first time a microfluidic system for the study of flocculation under well controlled conditions. In our microfluidic device (μFLOC), floc sizes and growth rates were monitored in real time using high-speed imaging and computational image analysis. The on-line and in situ detection allowed quantification of floc sizes and their growth kinetics. This eliminated the issues of sample handling, sample dispersion, and end-point measurements. We demonstrated the power of this approach by quantifying the growth rates of floc formation under forty different growth conditions by varying industrially relevant flocculating agents (pDADMAC, PEI, PEG), their concentration and dosage. Growth rates between 12.2 μm s−1 for a strongly cationic flocculant (pDADMAC) and 0.6 μm s−1 for a non-ionic flocculant (PEG) were observed, demonstrating the potential to rank flocculating conditions in a quantitative way. We have therefore created a screening tool to efficiently compare flocculating agents and rapidly find the best flocculating condition, which will significantly accelerate early bioprocess development

UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. © 2012 Kwon et al

Random attractors for degenerate stochastic partial differential equations

We prove the existence of random attractors for a large class of degenerate stochastic partial differential equations (SPDE) perturbed by joint additive Wiener noise and real, linear multiplicative Brownian noise, assuming only the standard assumptions of the variational approach to SPDE with compact embeddings in the associated Gelfand triple. This allows spatially much rougher noise than in known results. The approach is based on a construction of strictly stationary solutions to related strongly monotone SPDE. Applications include stochastic generalized porous media equations, stochastic generalized degenerate p-Laplace equations and stochastic reaction diffusion equations. For perturbed, degenerate p-Laplace equations we prove that the deterministic, infinite dimensional attractor collapses to a single random point if enough noise is added.Comment: 34 pages; The final publication is available at http://link.springer.com/article/10.1007%2Fs10884-013-9294-

The conceptualisation and measurement of DSM-5 Internet Gaming Disorder: the development of the IGD-20 Test

Background: Over the last decade, there has been growing concern about ‘gaming addiction’ and its widely documented detrimental impacts on a minority of individuals that play excessively. The latest (fifth) edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included nine criteria for the potential diagnosis of Internet Gaming Disorder (IGD) and noted that it was a condition that warranted further empirical study. Aim: The main aim of this study was to develop a valid and reliable standardised psychometrically robust tool in addition to providing empirically supported cut-off points. Methods: A sample of 1003 gamers (85.2% males; mean age 26 years) from 57 different countries were recruited via online gaming forums. Validity was assessed by confirmatory factor analysis (CFA), criterion-related validity, and concurrent validity. Latent profile analysis was also carried to distinguish disordered gamers from non-disordered gamers. Sensitivity and specificity analyses were performed to determine an empirical cut-off for the test. Results: The CFA confirmed the viability of IGD-20 Test with a six-factor structure (salience, mood modification, tolerance, withdrawal, conflict and relapse) for the assessment of IGD according to the nine criteria from DSM-5. The IGD-20 Test proved to be valid and reliable. According to the latent profile analysis, 5.3% of the total participants were classed as disordered gamers. Additionally, an optimal empirical cut-off of 71 points (out of 100) seemed to be adequate according to the sensitivity and specificity analyses carried

Predicting the adsorption behavior in bulk from metal clusters

The physicochemical properties of materials are directly related to their size. The ability to understand and eventually tailor the materials' properties over multiple length scales has always been of a primary research goal. Using quantum mechanical calculations and mathematical modeling, we establish a novel theoretical framework capable of predicting the catalytic behavior of bulk metals and alloys and specifically the adsorbate binding energy, using electronic structure information from sub-nanometer cluster models as input. These models demonstrate that bulk-phase concepts can be reproduced from clusters; a first step towards bridging the properties of materials at different length scales. © 2011 Elsevier B.V. All rights reserved

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al