REMOVING TECHNICAL VARIABILITY IN RNA-SEQ DATA USING CONDITIONAL QUANTILE NORMALIZATION

The ability to measure gene expression on a genome-wide scale is one of the most promising accomplishments in molecular biology. Microarrays, the technology that first permitted this, were riddled with problems due to unwanted sources of variability. Many of these problems are now mitigated, after a decade’s worth of statistical methodology development. The recently developed RNA sequencing (RNA-seq) technology has generated much excitement in part due to claims of reduced variability in comparison to microarrays. However, we show RNA-seq data demonstrates unwanted and obscuring variability similar to what was first observed in microarrays. In particular, we find GC-content has a strong sample specific effect on gene expression measurements that, if left uncorrected, leads to false positives in downstream results. We also report on commonly observed data distortions that demonstrate the need for data normalization. Here we describe statistical methodology that improves precision by 42% without loss of accuracy. Our resulting conditional quantile normalization (CQN) algorithm combines robust generalized regression to remove systematic bias introduced by deterministic features such as GC-content, and quantile normalization to correct for global distortions.

Temporary Internal Fixation for Ligamentous and Osseous Lisfranc Injuries: Outcome and Technical Tip

BACKGROUND Open rather than closed reduction and internal fixation as well as primary definitive arthrodesis are well accepted for ligamentous and osseous Lisfranc injuries. For ligamentous injuries, a better outcome after primary definitive partial arthrodesis has been published. METHODS Of 135 Lisfranc injuries that were treated from 1998 to 2012 with open reduction, temporary internal fixation by screws and plates, and restricted weight bearing in a lower leg cast for 3 months followed by an arch support for another 4 to 6 weeks, 29 ligamentous Lisfranc injuries were available for follow-up. They were compared with 29 osseous Lisfranc injuries matched in age and gender. RESULTS Between the groups, there were no significant differences in average age (39.9 vs 38 years) or in average follow-up time (8.3 vs 9.1 years). Also, no significant differences were seen in the AOFAS midfoot score (84 vs 85.3 points), the FFI pain scale (9.9 vs 14.9 points), SF 36 physical component (56.2 vs 53.9 points), SF 36 mental component (57 vs 56.4 points), or VAS for pain (1.6 vs 1.5 points). The FFI function scale was significantly lower in the ligamentous group (11.6 vs 19.5 points). Radiographically, loss of reduction was recorded 3 times in the ligamentous injuries and 4 times in the osseous injuries. Arthritis was mild/moderate/severe in 5/3/0 ligamentous injuries and in 7/2/1 osseous injuries, requiring 1 definitive secondary Lisfranc arthrodesis in each group. CONCLUSION With longer and conservative postoperative management, open reduction and temporary internal fixation in ligamentous and osseous Lisfranc injuries led to equal medium-term outcome. Inferior outcome in ligamentous injuries was not found. LEVEL OF EVIDENCE Level III, retrospective comparative cohort study.

Inequality in the Southern Mediterranean: A survey of selected countries. MEDPRO Technical Report No. 23/December 2012

This paper addresses the issues of current levels of inequality: their trends, determinants and future scenarios, demonstrating that welfare levels are measured by per capita consumption. Location, educational attainment and employment status have been identified as the key factors affecting levels of welfare and its distribution. A benefit incidence analysis was performed to investigate benefits of different deciles of per capita expenditure from education and health services. The inequality patterns in countries under investigation present significant variations; countries such as Turkey, Morocco and Tunisia show relatively high inequality while others, such as Egypt or Syria, show moderate to low inequality. Inequality in human development was addressed using the inequality-adjusted human development index (IHDI), introduced by Global HDR 2010. The average loss in the HDI due to inequality in all Arab countries under investigation is about 20%. Two reference scenarios (optimistic and pessimistic) were used to project future paths up to 2020 and 2030. The impact of positive growth is increasing inequality and a shrinking middle class. Results show that the rich benefit most from this growth path. The opposite trend is observed for the pessimistic scenario.

Identification, quantification and structuring of two-lane rural highway safety problems and solutions. Volume I - technical report. Final report.

Federal Highway Administration, Washington, D.C.

Simulation of nutrient loss from soils due to rainfall acidity /

Bibliography: p. 43-44.

The electrical admittance of a homogeneous polarized fully electroded circular disc, loss-less and mechanically free : analysis, including Rayleigh correction, data for routine determination of elastic modulus and Piezoelectric coupling, and discussion of limitation of correction, anisotrophy parameters involved, and deductions concerning dimensional standarization /

"ONR Contract No. Nonr-1055(00)."

Lameness, metabolic and digestive disorders, and technical efficiency in Danish dairy herds: a stochastic frontier production function approach

The relationship between reported treatments of lameness, metabolic disorders (milk fever, ketosis), digestive disorders, and technical efficiency (TE) was investigated using neutral and non-neutral stochastic frontier analysis (SFA). TE is estimated relative to the stochastic frontier production function for a sample of 574 Danish dairy herds collected in 1997. Contrary to most published results, but in line with the expected negative impact of disorders on the average cow milk production, herds reporting higher frequencies of milk fever are less technically efficient. Unexpectedly, however, the opposite results were observed for lameness, ketosis, and digestive disorders. The non-neutral stochastic frontier indicated that the opposite results are due to the relative. high productivities of inputs. The productivity of the cows is also reflected by the direction of impact of herd management variables. Whereas efficient farms replace cows more frequently, enroll heifers in production at an earlier age, and have shorter calving intervals, they also report higher frequency of disorder treatments. The average estimated energy corrected milk loss per cow is 1036, 451 and 242 kg for low, medium and high efficient farms. The study demonstrates the benefit of the stochastic frontier production function involving the estimation of individual technical efficiencies to evaluate farm performance and investigate the source of inefficiency. (C) 2004 Elsevier B.V. All rights reserved.

Surface acoustic wave devices with low loss and high frequency operation

This thesis describes an industrial research project carried out in collaboration with STC Components, Harlow, Essex. Technical and market trends in the use of surface acoustic wave (SAW) devices are reviewed. As a result, three areas not previously addressed by STC were identified: lower insertion loss designs, higher operating frequencies and improved temperature dependent stability. A review of the temperature performance of alternative lower insertion loss designs,shows that greater use could be made of the on-site quartz growing plant. Data is presented for quartz cuts in the ST-AT range. This data is used to modify the temperature performance of a SAW filter. Several recently identified quartz orientations have been tested. These are SST, LST and X33. Problems associated with each cut are described and devices demonstrated. LST quartz, although sensitive to accuracy of cut, is shown to have an improved temperature coefficient over the normal ST orientation. Results show that its use is restricted due to insertion loss variations with temperature. Effects associated with split-finger transducers on LST-quartz are described. Two low-loss options are studied, coupled resonator filters for very narrow bandwidth applications and single phase unidirectional transducers (SPUDT) for fractional bandwidths up to about 1%. Both designs can be implemented with one quarter wavelength transducer geometries at operating frequencies up to 1GHz. The SPUDT design utilised an existing impulse response model to provide analysis of ladder or rung transducers. A coupled resonator filter at 400MHz is demonstrated with a matched insertion loss of less than 3.5dB and bandwidth of 0.05%. A SPUDT device is designed as a re-timing filter for timing extraction in a long haul PCM transmission system. Filters operating at 565MHz are demonstrated with insertion losses of less than 6dB. This basic SPUDT design is extended to a maximally distributed version and demonstrated at 450MHz with 9.8dB insertion loss.

Low loss depressed cladding waveguide inscribed in YAG:Nd single crystal by femtosecond pulses

A depressed cladding waveguide with record low loss of 0.12 dB/cm is inscribed in YAG:Nd(0.3at.%). It is shown that depressed cladding is a dominating factor in waveguide formation, and mechanical stress has a minor contribution. © 2012 OSA.

WDM transmission at 2μm over low-loss hollow core photonic bandgap fiber

World's first demonstration of WDM transmission in a HC-PBGF at the predicted low loss region of 2m is presented. A total capacity of 16 Gbit/s is achieved using 1×8.5 Gbit/s and 3×2.5 Gbit/s channels modulated using NRZ OOK over 290 meters of hollow core fiber. © 2013 OSA.

Dispersionless low-loss miniature slow light delay lines based on optical fibers

A miniature slow light delay line with the record large delay time, small transmission loss, dispersion, and effective speed of light is proposed and demonstrated using the SNAP (Surface Nanoscale Axial Photonics) technology. © 2014 OSA.

Record small and low loss slow light delay lines and dispersion compensators

Record small and low loss slow light optical signal processing devices are proposed and demonstrated using the recently invented Surface Nanoscale Axial Photonics (SNAP) technology.

Femtosecond laser inscription of fiber bragg gratings with low insertion loss and minor polarization dependence

The inscription of low insertion loss and negligibly polarization dependent fiber Bragg gratings inscribed using a femtosecond laser system is reported. Insertion losses were <0.4dB/20mm and polarization wavelength shift of <5pm, with transmission changes <0.1dB. © 2010 Optical Society of America.