A general approach to simultaneous model fitting and variable elimination in response models for biological data with many more variables than observations

<p>Abstract</p> <p>Background</p> <p>With the advent of high throughput biotechnology data acquisition platforms such as micro arrays, SNP chips and mass spectrometers, data sets with many more variables than observations are now routinely being collected. Finding relationships between response variables of interest and variables in such data sets is an important problem akin to finding needles in a haystack. Whilst methods for a number of response types have been developed a general approach has been lacking.</p> <p>Results</p> <p>The major contribution of this paper is to present a unified methodology which allows many common (statistical) response models to be fitted to such data sets. The class of models includes virtually any model with a linear predictor in it, for example (but not limited to), multiclass logistic regression (classification), generalised linear models (regression) and survival models. A fast algorithm for finding sparse well fitting models is presented. The ideas are illustrated on real data sets with numbers of variables ranging from thousands to millions. R code implementing the ideas is available for download.</p> <p>Conclusion</p> <p>The method described in this paper enables existing work on response models when there are less variables than observations to be leveraged to the situation when there are many more variables than observations. It is a powerful approach to finding parsimonious models for such datasets. The method is capable of handling problems with millions of variables and a large variety of response types within the one framework. The method compares favourably to existing methods such as support vector machines and random forests, but has the advantage of not requiring separate variable selection steps. It is also works for data types which these methods were not designed to handle. The method usually produces very sparse models which make biological interpretation simpler and more focused.</p

Single-shot compressed ultrafast photography at one hundred billion frames per second

The capture of transient scenes at high imaging speed has been long sought by photographers, with early examples being the well known recording in 1878 of a horse in motion and the 1887 photograph of a supersonic bullet. However, not until the late twentieth century were breakthroughs achieved in demonstrating ultrahigh-speed imaging (more than 10^5 frames per second). In particular, the introduction of electronic imaging sensors based on the charge-coupled device (CCD) or complementary metal–oxide–semiconductor (CMOS) technology revolutionized high-speed photography, enabling acquisition rates of up to 10^7 frames per second. Despite these sensors’ widespread impact, further increasing frame rates using CCD or CMOS technology is fundamentally limited by their on-chip storage and electronic readout speed. Here we demonstrate a two-dimensional dynamic imaging technique, compressed ultrafast photography (CUP), which can capture non-repetitive time-evolving events at up to 10^(11) frames per second. Compared with existing ultrafast imaging techniques, CUP has the prominent advantage of measuring an x–y–t (x, y, spatial coordinates; t, time) scene with a single camera snapshot, thereby allowing observation of transient events with temporal resolution as tens of picoseconds. Furthermore, akin to traditional photography, CUP is receive-only, and so does not need the specialized active illumination required by other single-shot ultrafast imagers. As a result, CUP can image a variety of luminescent—such as fluorescent or bioluminescent—objects. Using CUP, we visualize four fundamental physical phenomena with single laser shots only: laser pulse reflection and refraction, photon racing in two media, and faster-than-light propagation of non-information (that is, motion that appears faster than the speed of light but cannot convey information). Given CUP’s capability, we expect it to find widespread applications in both fundamental and applied sciences, including biomedical research

Anthropometric, biochemical and clinical assessment of malnutrition in Malaysian patients with advanced cirrhosis

<p>Abstract</p> <p>Background</p> <p>There is limited data on the nutritional status of Asian patients with various aetiologies of cirrhosis. This study aimed to determine the prevalence of malnutrition and to compare nutritional differences between various aetiologies.</p> <p>Methodology</p> <p>A cross-sectional study of adult patients with decompensated cirrhosis was conducted. Nutritional status was assessed using standard anthropometry, serum visceral proteins and subjective global assessment (SGA).</p> <p>Results</p> <p>Thirty six patients (mean age 59.8 ± 12.8 years; 66.7% males; 41.6% viral hepatitis; Child-Pugh C 55.6%) with decompensated cirrhosis were recruited. Malnutrition was prevalent in 18 (50%) patients and the mean caloric intake was low at 15.2 kcal/kg/day. SGA grade C, as compared to SGA grade B, demonstrated significantly lower anthropometric values in males (BMI 18.1 ± 1.6 vs 26.3 ± 3.5 kg/m2, p < 0.0001; MAMC 19.4 ± 1.5 vs 24.5 ± 3.6 cm, p = 0.002) and females (BMI 19.4 ± 2.7 vs 28.9 ± 4.3, p = 0.001; MAMC 18.0 ± 0.9 vs 28.1 ± 3.6, p < 0.0001), but not with visceral proteins. The SGA demonstrated a trend towards more malnutrition in Child-Pugh C compared to Child-Pugh B liver cirrhosis (40% grade C vs 25% grade C, p = 0.48). Alcoholic cirrhosis had a higher proportion of SGA grade C (41.7%) compared to viral (26.7%) and cryptogenic (28.6%) cirrhosis, but this was not statistically significant.</p> <p>Conclusion</p> <p>Significant malnutrition in Malaysian patients with advanced cirrhosis is common. Alcoholic cirrhosis may have more malnutrition compared to other aetiologies of cirrhosis.</p

Effects of chronic ascariasis and trichuriasis on cytokine production and gene expression in human blood: a cross-sectional study.

Background Chronic soil-transmitted helminth (STH) infections are associated with effects on systemic immune responses that could be caused by alterations in immune homeostasis. To investigate this, we measured the impact in children of STH infections on cytokine responses and gene expression in unstimulated blood. Methodology/Principal Findings Sixty children were classified as having chronic, light, or no STH infections. Peripheral blood mononuclear cells were cultured in medium for 5 days to measure cytokine accumulation. RNA was isolated from peripheral blood and gene expression analysed using microarrays. Different infection groups were compared for the purpose of analysis: STH infection (combined chronic and light vs. uninfected groups) and chronic STH infection (chronic vs. combined light and uninfected groups). The chronic STH infection effect was associated with elevated production of GM-CSF (P = 0.007), IL-2 (P = 0.03), IL-5 (P = 0.01), and IL-10 (P = 0.01). Data reduction suggested that chronic infections were primarily associated with an immune phenotype characterized by elevated IL-5 and IL-10, typical of a modified Th2-like response. Chronic STH infections were associated with the up-regulation of genes associated with immune homeostasis (IDO, P = 0.03; CCL23, P = 0.008, HRK, P = 0.005), down-regulation of microRNA hsa-let-7d (P = 0.01) and differential regulation of several genes associated with granulocyte-mediated inflammation (IL-8, down-regulated, P = 0.0002; RNASE2, up-regulated, P = 0.009; RNASE3, up-regulated, p = 0.03). Conclusions/Significance Chronic STH infections were associated with a cytokine response indicative of a modified Th2 response. There was evidence that STH infections were associated with a pattern of gene expression suggestive of the induction of homeostatic mechanisms, the differential expression of several inflammatory genes and the down-regulation of microRNA has-let-7d. Effects on immune homeostasis and the development of a modified Th2 immune response during chronic STH infections could explain the systemic immunologic effects that have been associated with these infections such as impaired immune responses to vaccines and the suppression of inflammatory diseases

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO