Estimating influenza incidence using search query deceptiveness and generalized ridge regression

Seasonal influenza is a sometimes surprisingly impactful disease, causing thousands of deaths per year along with much additional morbidity. Timely knowledge of the outbreak state is valuable for managing an effective response. The current state of the art is to gather this knowledge using in-person patient contact. While accurate, this is time-consuming and expensive. This has motivated inquiry into new approaches using internet activity traces, based on the theory that lay observations of health status lead to informative features in internet data. These approaches risk being deceived by activity traces having a coincidental, rather than informative, relationship to disease incidence; to our knowledge, this risk has not yet been quantitatively explored. We evaluated both simulated and real activity traces of varying deceptiveness for influenza incidence estimation using linear regression. We found that deceptiveness knowledge does reduce error in such estimates, that it may help automatically-selected features perform as well or better than features that require human curation, and that a semantic distance measure derived from the Wikipedia article category tree serves as a useful proxy for deceptiveness. This suggests that disease incidence estimation models should incorporate not only data about how internet features map to incidence but also additional data to estimate feature deceptiveness. By doing so, we may gain one more step along the path to accurate, reliable disease incidence estimation using internet data. This capability would improve public health by decreasing the cost and increasing the timeliness of such estimates.Comment: 27 pages, 8 figure

Empirical Validation of a New Data Product from the Interstellar Boundary Explorer Satellite

Since 2008, the Interstellar Boundary Explorer (IBEX) satellite has been gathering data on heliospheric energetic neutral atoms (ENAs) while being exposed to various sources of background noise, such as cosmic rays and solar energetic particles. The IBEX mission initially released only a qualified triple-coincidence (qABC) data product, which was designed to provide observations of ENAs free of background contamination. Further measurements revealed that the qABC data was in fact susceptible to contamination, having relatively low ENA counts and high background rates. Recently, the mission team considered releasing a certain qualified double-coincidence (qBC) data product, which has roughly twice the detection rate of the qABC data product. This paper presents a simulation-based validation of the new qBC data product against the already-released qABC data product. The results show that the qBCs can plausibly be said to share the same signal rate as the qABCs up to an average absolute deviation of 3.6%. Visual diagnostics at an orbit, map, and full mission level provide additional confirmation of signal rate coherence across data products. These approaches are generalizable to other scenarios in which one wishes to test whether multiple observations could plausibly be generated by some underlying shared signal

Incorporating expression data in metabolic modeling: a case study of lactate dehydrogenase

Integrating biological information from different sources to understand cellular processes is an important problem in systems biology. We use data from mRNA expression arrays and chemical kinetics to formulate a metabolic model relevant to K562 erythroleukemia cells. MAP kinase pathway activation alters the expression of metabolic enzymes in K562 cells. Our array data show changes in expression of lactate dehydrogenase (LDH) isoforms after treatment with phorbol 12-myristate 13-acetate (PMA), which activates MAP kinase signaling. We model the change in lactate production which occurs when the MAP kinase pathway is activated, using a non-equilibrium, chemical-kinetic model of homolactic fermentation. In particular, we examine the role of LDH isoforms, which catalyze the conversion of pyruvate to lactate. Changes in the isoform ratio are not the primary determinant of the production of lactate. Rather, the total concentration of LDH controls the lactate concentration.Comment: In press, Journal of Theoretical Biology. 27 pages, 9 figure

The early evolution of the H-free process

The H-free process, for some fixed graph H, is the random graph process defined by starting with an empty graph on n vertices and then adding edges one at a time, chosen uniformly at random subject to the constraint that no H subgraph is formed. Let G be the random maximal H-free graph obtained at the end of the process. When H is strictly 2-balanced, we show that for some c>0, with high probability as $n \to \infty$, the minimum degree in G is at least $cn^{1-(v_H-2)/(e_H-1)}(\log n)^{1/(e_H-1)}$. This gives new lower bounds for the Tur\'an numbers of certain bipartite graphs, such as the complete bipartite graphs $K_{r,r}$ with $r \ge 5$. When H is a complete graph $K_s$ with $s \ge 5$ we show that for some C>0, with high probability the independence number of G is at most $Cn^{2/(s+1)}(\log n)^{1-1/(e_H-1)}$. This gives new lower bounds for Ramsey numbers R(s,t) for fixed $s \ge 5$ and t large. We also obtain new bounds for the independence number of G for other graphs H, including the case when H is a cycle. Our proofs use the differential equations method for random graph processes to analyse the evolution of the process, and give further information about the structure of the graphs obtained, including asymptotic formulae for a broad class of subgraph extension variables.Comment: 36 page

Electron flux models for different energies at geostationary orbit

Forecast models were derived for energetic electrons at all energy ranges sampled by the third-generation Geostationary Operational Environmental Satellites (GOES). These models were based on Multi-Input Single-Output Nonlinear Autoregressive Moving Average with Exogenous inputs methodologies. The model inputs include the solar wind velocity, density and pressure, the fraction of time that the interplanetary magnetic field (IMF) was southward, the IMF contribution of a solar wind-magnetosphere coupling function proposed by Boynton et al. (2011b), and the Dst index. As such, this study has deduced five new 1 h resolution models for the low-energy electrons measured by GOES (30–50 keV, 50–100 keV, 100–200 keV, 200–350 keV, and 350–600 keV) and extended the existing >800 keV and >2 MeV Geostationary Earth Orbit electron fluxes models to forecast at a 1 h resolution. All of these models were shown to provide accurate forecasts, with prediction efficiencies ranging between 66.9% and 82.3%

Attitudes towards complementary and alternative medicine in chronic pain syndromes: a questionnaire-based comparison between primary headache and low back pain

<p>Abstract</p> <p>Background</p> <p>Complementary and Alternative Medicine (CAM) is widely used and popular among patients with primary headache or low back pain (LBP). Aim of the study was to analyze attitudes of headache and LBP patients towards the use of CAM.</p> <p>Methods</p> <p>Two questionnaire-based surveys were applied comparing 432 primary headache and 194 LBP patients.</p> <p>Results</p> <p>In total, 84.75% of all patients reported use of CAM; with significantly more LBP patients. The most frequently-used CAM therapies in headache were acupuncture (71.4%), massages (56.4%), and thermotherapy (29.2%), in LBP thermotherapy (77.4%), massages (62.7%), and acupuncture (51.4%). The most frequent attitudes towards CAM use in headache vs. LBP: "leave nothing undone" (62.5% vs. 52.1%; p = 0.006), "take action against the disease" (56.8% vs. 43.2%; p = 0.006). Nearly all patients with previous experience with CAM currently use CAM in both conditions (93.6% in headache; 100% in LBP). However, the majority of the patients had no previous experience.</p> <p>Conclusion</p> <p>Understanding motivations for CAM treatment is important, because attitudes derive from wishes for non-pharmacological treatment, to be more involved in treatment and avoid side effects. Despite higher age and more permanent pain in LBP, both groups show high use of CAM with only little specific difference in preferred methods and attitudes towards CAM use. This may reflect deficits and unfulfilled goals in conventional treatment. Maybe CAM can decrease the gap between patients' expectations about pain therapy and treatment reality, considering that both conditions are often chronic diseases, causing high burdens for daily life.</p

Genomic copy number and expression patterns in testicular germ cell tumours

Testicular germ cell tumours of adults and adolescents (TGCT) include seminomas (SE) and nonseminomas (NS), with spermatocytic seminomas (SSE) representing a distinct entity in older men. SE and NS have gain of 12p material in all cases, whereas SSE are associated with overrepresentation of chromosome 9. Here, we compare at the chromosomal level, copy number imbalances with global expression changes, identified by comparative expressed sequence hybridisation analyses, in seven SE, one combined tumour, seven NS and seven cell lines. Positive correlations were found consistent with copy number as a main driver of expression change, despite reported differences in methylation status in SE and NS. Analysis of chromosomal copy number and expression data could not distinguish between SE and NS, in-keeping with a similar genetic pathogenesis. However, increased expression from 4q22, 5q23.2 and 9p21 distinguished SSE from SE and NS and decreased copy number and expression from 2q36–q37 and 6q24 was a specific feature of NS-derived cell lines. Our analysis also highlights 19 regions with both copy number and expression imbalances in greater than 40% of cases. Mining available expression array data identified genes from these regions as candidates for involvement in TGCT development. Supplementary data is available at http://www.crukdmf.icr.ac.uk/array/array.html

Modulation of Glucose Transporter 1 (GLUT1) Expression Levels Alters Mouse Mammary Tumor Cell Growth In Vitro and In Vivo

Tumor cells exhibit an altered metabolism characterized by elevated aerobic glycolysis and lactate secretion which is supported by an increase in glucose transport and consumption. We hypothesized that reducing or eliminating the expression of the most prominently expressed glucose transporter(s) would decrease the amount of glucose available to breast cancer cells thereby decreasing their metabolic capacity and proliferative potential

Hypoxia induces differential translation of enolase/MBP-1

<p>Abstract</p> <p>Background</p> <p>Hypoxic microenvironments in tumors contribute to transformation, which may alter metabolism, growth, and therapeutic responsiveness. The α-enolase gene encodes both a glycolytic enzyme (α-enolase) and a DNA-binding tumor suppressor protein, c-myc binding protein (MBP-1). These divergent α-enolase gene products play central roles in glucose metabolism and growth regulation and their differential regulation may be critical for tumor adaptation to hypoxia. We have previously shown that MBP-1 and its binding to the c-myc P₂promoter regulates the metabolic and cellular growth changes that occur in response to altered exogenous glucose concentrations.</p> <p>Results</p> <p>To examine the regulation of α-enolase and MBP-1 by a hypoxic microenvironment in breast cancer, MCF-7 cells were grown in low, physiologic, or high glucose under 1% oxygen. Our results demonstrate that adaptation to hypoxia involves attenuation of MBP-1 translation and loss of MBP-1-mediated regulation of c-myc transcription, evidenced by decreased MBP-1 binding to the c-myc P₂promoter. This allows for a robust increase in c-myc expression, "early c-myc response", which stimulates aerobic glycolysis resulting in tumor acclimation to oxidative stress. Increased α-enolase mRNA and preferential translation/post-translational modification may also allow for acclimatization to low oxygen, particularly under low glucose concentrations.</p> <p>Conclusions</p> <p>These results demonstrate that malignant cells adapt to hypoxia by modulating α-enolase/MBP-1 levels and suggest a mechanism for tumor cell induction of the hyperglycolytic state. This important "feedback" mechanism may help transformed cells to escape the apoptotic cascade, allowing for survival during limited glucose and oxygen availability.</p