bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPROVEMENT IN THERMAL DEGRADATION OF ZnO PHOTODETECTOR BY EMBEDDING SILVER OXIDE NANOPARTICLES
Authors: HU ZHAN-SHUO , HUNG FEI-YI , CHEN KUAN-JEN , CHANG SHOOU-JINN , HSIEH WEI-KANG , LIAO TSAI-YU
Published: November 2012

The degraded performance of annealed ZnO -based photodetector can be improved by embedding an Ag interlayer. The Ag interlay converted to Ag2O during ZnO deposition. After Ag2O nanoparticles formed, the interface between ZnO and Ag2O produced band-bending to redistribute charges and increase the Schottky barrier between the electrical contact and ZnO . The excess Ag interlayer created lattice defects, causing the dark current to increase slightly. The increasing visible PL intensity of annealed ZnO , with the increasing Ag interlayer, clarified the transfer of the photo-generated electron.
The Promise of Combining Inhibition of PI3K and PARP as Cancer Therapy
Authors: Rehman Farah L. , Lord Christopher J. , Ashworth Alan
Published: November 2012

Analyses of in vitro and patient-derived in vivo models of breast cancer reveal that a combination of inhibitors of the enzymes PARP and phosphoinositide 3-kinase (PI3K) is a potentially effective treatment regimen for breast cancer tumors with elevated activity of the PI3K pathway. Cancer Discov; 2(11); 982–4. ©2012 AACR.

Commentary on Ibrahim et al., p. 1036.

Commentary on Juvekar et al., p. 1048.
The Inflow to Tropical Cyclone Humberto (2001) as Viewed with Azimuth–Height Surfaces over Three Days
Authors: Barnes Gary M. , Dolling Klaus P.
Published: November 2012

The deployment of 228 global positioning system dropwindsondes (GPS sondes), over three consecutive days in Tropical Cyclone Humberto (2001), allows for the creation of azimuth–height (ϕ–z) surfaces from sea level to 3-km altitude at 0.25° and 0.5° latitude distance from the storm center. The authors estimate the radial flow along these ϕ–z surfaces to diagnose the mass flux through said surfaces as Humberto deepens from 1000 to 983 hPa from the first to the second day, then fills to 992 hPa by the third day. As the tropical cyclone (TC) intensifies the width, depth, and rate of inflow increase. The inflow remains a wavenumber-1 pattern throughout the three days. The center of the inflow rotates clockwise over this period following the expected forcing due to both the tropical cyclone motion and deep layer shear vectors. Net vertical mass flux, based on continuity within a given volume, is correlated with TC intensity only for the inner 0.25° ϕ–z surface. Slightly farther from the center, at 0.5° radial distance, the net mass flux is much larger but is not correlated with intensity. The rainbands that exist between the 0.25° and the 0.50° rings are ineffective at either creating or maintaining a warm core and lowering the surface pressure. The authors speculate that the warming associated with convective bands at larger radii is more easily eroded by the strong wind shear; convective bands nearer the center produce a more complete wind field that protects the warm core.
Spread Calibration of Ensemble MOS Forecasts
Authors: Veenhuis Bruce A.
Published: November 2012

Ensemble forecasting systems often contain systematic biases and spread deficiencies that can be corrected by statistical postprocessing. This study presents an improvement to an ensemble statistical postprocessing technique, called ensemble kernel density model output statistics (EKDMOS). EKDMOS uses model output statistics (MOS) equations and spread–skill relationships to generate calibrated probabilistic forecasts. The MOS equations are multiple linear regression equations developed by relating observations to ensemble mean-based predictors. The spread–skill relationships are one-term linear regression equations that predict the expected accuracy of the ensemble mean given the ensemble spread. To generate an EKDMOS forecast, the MOS equations are applied to each ensemble member. Kernel density fitting is used to create a probability density function (PDF) from the ensemble MOS forecasts. The PDF spread is adjusted to match the spread predicted by the spread–skill relationship, producing a calibrated forecast. The improved EKDMOS technique was used to produce probabilistic 2-m temperature forecasts from the North American Ensemble Forecast System (NAEFS) over the period 1 October 2007–31 March 2010. The results were compared with an earlier spread adjustment technique, as well as forecasts generated by rank sorting the bias-corrected ensemble members. Compared to the other techniques, the new EKDMOS forecasts were more reliable, had a better calibrated spread–error relationship, and showed increased day-to-day spread variability.
Evaluation of a Wind-Wave System for Ensemble Tropical Cyclone Wave Forecasting. Part I: Winds
Authors: Lazarus Steven M. , Wilson Samuel T. , Splitt Michael E. , Zarillo Gary A.
Published: November 2012

A computationally efficient method of producing tropical cyclone (TC) wind analyses is developed and tested, using a hindcast methodology, for 12 Gulf of Mexico storms. The analyses are created by blending synthetic data, generated from a simple parametric model constructed using extended best-track data and climatology, with a first-guess field obtained from the NCEP–NCAR North American Regional Reanalysis (NARR). Tests are performed whereby parameters in the wind analysis and vortex model are varied in an attempt to best represent the TC wind fields. A comparison between nonlinear and climatological estimates of the TC size parameter indicates that the former yields a much improved correlation with the best-track radius of maximum wind rm. The analysis, augmented by a pseudoerror term that controls the degree of blending between the NARR and parametric winds, is tuned using buoy observations to calculate wind speed root-mean-square deviation (RMSD), scatter index (SI), and bias. The bias is minimized when the parametric winds are confined to the inner-core region. Analysis wind statistics are stratified within a storm-relative reference frame and by radial distance from storm center, storm intensity, radius of maximum wind, and storm translation speed. The analysis decreases the bias and RMSD in all quadrants for both moderate and strong storms and is most improved for storms with an rm of less than 20 n mi. The largest SI reductions occur for strong storms and storms with an rm of less than 20 n mi. The NARR impacts the analysis bias: when the bias in the former is relatively large, it remains so in the latter.
Weather and Individual Happiness
Authors: Tsutsui Yoshiro
Published: November 2012

This paper investigates the influence of weather on happiness. While previous studies have examined climatic influence by comparing the well-being of people living in different regions, this paper focuses on how daily changes in weather affect individuals living in a single location. The dataset consists of 516 days of data on 75 students from Osaka University. Daily information on outside events, as well as the daily physical condition and individual characteristics of the respondents, are used as controls. Subjective happiness is related to temperature: in a quadratic model, happiness is maximized at 13.9°C. The effects of other meteorological variables—humidity, wind speed, precipitation, and sunshine—are not significant. The sensitivity of happiness to temperature also depends on attributes such as sex, age, and academic department. Happiness is more strongly affected by current temperature than by average temperature over the day. While enjoyment (a positive affect measure) is affected by weather in a similar way to happiness, sadness and depression (negative affect measures) behave somewhat differently.
The Dynamics and Dilemma of Workplace Trade Union Reform in China: The Case of the Honda Workers’ Strike
Authors: Chan Chris King-Chi , Hui Elaine Sio-Ieng
Published: November 2012

Based on a case study of the Honda workers’ strike and its impact on workplace industrial relations, this article explores the potential of and barriers to workplace trade union reform in China. A rise in workers’ collective actions has put political pressure on the All China Federation of Trade Unions to promote effective trade unionism and create a vital foundation for exercising democratic union representation in the workplace. The main barrier to effective workplace unionism, however, is the lack of external support for workers’ unionization efforts. On the one hand, the lower-level local trade unions fail to comply with their legal responsibility because of their bureaucratic nature and structural integration into the patron–client relationship between the local state and the global capital. On the other hand, support for workers from civil society is handicapped by the party-state’s opposition to independent labour organizing. This dilemma has forced the higher trade union federation to intervene directly in workplace trade union reform and promote state-led wage bargaining.
Statistical distributions of test statistics used for quantitative trait association mapping in structured populations
Authors: Teyssèdre Simon , Elsen Jean-Michel , Ricard Anne
Published: November 2012

Background

Spurious associations between single nucleotide polymorphisms and phenotypes are a major issue in genome-wide association studies and have led to underestimation of type 1 error rate and overestimation of the number of quantitative trait loci found. Many authors have investigated the influence of population structure on the robustness of methods by simulation. This paper is aimed at developing further the algebraic formalization of power and type 1 error rate for some of the classical statistical methods used: simple regression, two approximate methods of mixed models involving the effect of a single nucleotide polymorphism (SNP) and a random polygenic effect (GRAMMAR and FASTA) and the transmission/disequilibrium test for quantitative traits and nuclear families. Analytical formulae were derived using matrix algebra for the first and second moments of the statistical tests, assuming a true mixed model with a polygenic effect and SNP effects.

Results

The expectation and variance of the test statistics and their marginal expectations and variances according to the distribution of genotypes and estimators of variance components are given as a function of the relationship matrix and of the heritability of the polygenic effect. These formulae were used to compute type 1 error rate and power for any kind of relationship matrix between phenotyped and genotyped individuals for any level of heritability. For the regression method, type 1 error rate increased with the variability of relationships and with heritability, but decreased with the GRAMMAR method and was not affected with the FASTA and quantitative transmission/disequilibrium test methods.

Conclusions

The formulae can be easily used to provide the correct threshold of type 1 error rate and to calculate the power when designing experiments or data collection protocols. The results concerning the efficacy of each method agree with simulation results in the literature but were generalized in this work. The power of the GRAMMAR method was equal to the power of the FASTA method at the same type 1 error rate. The power of the quantitative transmission/disequilibrium test was low. In conclusion, the FASTA method, which is very close to the full mixed model, is recommended in association mapping studies.
iMS2Flux– a high–throughput processing tool for stable isotope labeled mass spectrometric data used for metabolic flux analysis
Authors: Poskar C Hart , Huege Jan , Krach Christian , Franke Mathias , Shachar-Hill Yair , Junker Björn H
Published: November 2012

Background

Metabolic flux analysis has become an established method in systems biology and functional genomics. The most common approach for determining intracellular metabolic fluxes is to utilize mass spectrometry in combination with stable isotope labeling experiments. However, before the mass spectrometric data can be used it has to be corrected for biases caused by naturally occurring stable isotopes, by the analytical technique(s) employed, or by the biological sample itself. Finally the MS data and the labeling information it contains have to be assembled into a data format usable by flux analysis software (of which several dedicated packages exist). Currently the processing of mass spectrometric data is time-consuming and error-prone requiring peak by peak cut-and-paste analysis and manual curation. In order to facilitate high-throughput metabolic flux analysis, the automation of multiple steps in the analytical workflow is necessary.

Results

Here we describe iMS2Flux, software developed to automate, standardize and connect the data flow between mass spectrometric measurements and flux analysis programs. This tool streamlines the transfer of data from extraction via correction tools to 13C-Flux software by processing MS data from stable isotope labeling experiments. It allows the correction of large and heterogeneous MS datasets for the presence of naturally occurring stable isotopes, initial biomass and several mass spectrometry effects. Before and after data correction, several checks can be performed to ensure accurate data. The corrected data may be returned in a variety of formats including those used by metabolic flux analysis software such as 13CFLUX, OpenFLUX and 13CFLUX2.

Conclusion

iMS2Flux is a versatile, easy to use tool for the automated processing of mass spectrometric data containing isotope labeling information. It represents the core framework for a standardized workflow and data processing. Due to its flexibility it facilitates the inclusion of different experimental datasets and thus can contribute to the expansion of flux analysis applications.
Testing of human papillomavirus in lung cancer and non-tumor lung tissue
Authors: Galvan Antonella , Noci Sara , Taverna Francesca , Lombardo Claudia , Franceschi Silvia , Pastorino Ugo , Dragani Tommaso A
Published: November 2012

Background

Risk factors for lung cancer, such as cigarette smoking, environmental pollution, asbestos, and genetic determinants, are well-known, whereas involvement of the human papillomavirus (HPV) is still unclear.

Methods

We examined a series of 100 lung cancer patients from Italy and the UK for the presence of HPV DNA in both lung tumor specimens and adjacent non-tumoral specimens from the same patients. Thirty-five of the most clinically relevant HPV types were assayed using PCR amplification of the highly conserved L1 region of the viral genome followed by hybridization with specific probes.

Results

No HPV was detected in tumor specimens nor in normal lung tissue of any patient.

Conclusions

These data indicate that, in this Western series, HPV is not associated with the risk of lung cancer. Our findings will help refine estimates of lung cancer risk in patients affected by a common viral infection involved in other types of human cancer.
Reliability and validity of self-assessment of mouth opening: a validation study
Authors: Saund Daniel Satnam Singh , Pearson David , Dietrich Thomas
Published: November 2012

Background

The objective of this study was to evaluate the reproducibility and validity of patients’ mouth opening measurements in a research setting.

Methods

Firstly, 68 patients made repeated self-measurements of mouth opening using a cardboard scale (Therabite Range of Motion Scale – TRMS). Secondly, 80 patients enrolled in a clinical trial on morbidity after lower third molar surgery, made daily assessments during the postoperative week. Patients’ measurements were then compared to gold-standard clinicians’ measurements.

Results

Reliability of patients’ measurements was excellent with an intraclass correlation coefficient of 0.92. The patient’s measurements correlated well with the gold-standard clinician’s measurements, both for the first 68 patients (Pearson’s rho ranging from 0.86 to 0.90, p < 0.0001) as well as for the 80 patients enrolled in the clinical trial (rho = 0.82, p < 0.0001 at day 2, rho = 0.83, p < 0.0001 at final visit).

Conclusions

TRMS can be used by patients to produce reproducible and valid mouth opening measurements.
The effect of acupuncture on stroke recovery: study protocol for a randomized controlled trial
Authors: Liu Huilin , Zhang Dangsheng , Tan Xiuge , Yang Daqing , Wang Guiling , Zhao Yin , Wen Yali , Shi Guangxia , Wang Linpeng
Published: November 2012

Background

Stroke is one of the leading causes of death and disability in China. Current treatments for stroke are limited and achieve no optimal effect. Acupuncture is widely used in the treatment of stroke and in improving the quality of life for patients in China. In most previous clinical studies, the effects of acupuncture have been diverse, and few well-designed randomized controlled trials have been conducted to investigate the long-term effect of acupuncture on acute stroke recovery.

Method

Three hundred and twenty eight subjects with acute cerebral apoplexy will be recruited. The patients will be randomized into two different groups: the intervention group will receive acupuncture treatment together with Western standard treatment for 2 weeks plus the secondary prevention treatment for 22 weeks; the control group will receive only the Western standard treatment for 2 weeks and the secondary prevention treatment for 22 weeks. The primary outcome measures are Barthel Index and the Stroke-Specific Quality Of Life. The secondary outcome measures are the National Institutes of Health Stroke Scale and Modified Rankin Scale. All assessments will be conducted at the baseline and at weeks 4, 12 and 24 of follow-up.

Discussion

This study will evaluate the effects of acupuncture on the long-term recovery of acute stroke and on improving the quality of life of the patients. The results of this study will help establish optimal integrated therapeutic strategies for patients with stroke.

Trial registration

Current Controlled Trials ISRCTN29932220
Best proximity point theorems for reckoning optimal approximate solutions
Authors: Basha S Sadiq , Shahzad N , Jeyaraj R
Published: November 2012

Given a non-self mapping from A to B, where A and B are subsets of a metric space, in order to compute an optimal approximate solution of the equation

S
x
=
x

, a best proximity point theorem probes into the global minimization of the error function

x
⟶
d
(
x
,
S
x
)

corresponding to approximate solutions of the equation

S
x
=
x

. This paper presents a best proximity point theorem for generalized contractions, thereby furnishing optimal approximate solutions, called best proximity points, to some non-linear equations. Also, an iterative algorithm is presented to compute such optimal approximate solutions.

MSC:90C26, 90C30, 41A65, 46B20, 47H10, 54H25.
Serological and molecular investigation into the role of wild birds in the epidemiology of West Nile virus in Greece
Authors: Valiakos George , Touloudi Antonia , Athanasiou Labrini V , Giannakopoulos Alexios , Iacovakis Christos , Birtsas Periklis , Spyrou Vassiliki , Dalabiras Zisis , Petrovska Liljana , Billinis Charalambos
Published: November 2012

Background

A West Nile virus (WNV) disease outbreak occurred in 2010 in northern Greece with a total of 262 laboratory-confirmed human cases and 35 deaths. A serological and molecular surveillance was conducted on samples of hunter-harvested wild birds prior to and during the outbreak.

Findings

Serum and tissue samples from 295 resident and migratory wild birds, hunter-harvested during the 2009–2010 and 2010–2011 hunting seasons at the epicenter of the outbreak in northern Greece, were tested for the presence of WNV-specific antibodies by immunofluorescence assay and virus neutralization test. WNV neutralizing antibodies were detected in 53 avian samples. Fourteen positive sera were obtained from birds hunter-harvested up to 8 months prior to the human outbreak. Specific genetic determinants of virulence (His249Pro NS3 mutation, E-glycosylation motif) were recognized in a WNV lineage 2 strain isolated from a hunter-harvested Eurasian magpie and a nucleotide mismatch was revealed between this strain and a mosquito WNV strain isolated one month earlier in the same area.

Conclusions

This is the first report regarding exposure of wild birds to WNV prior to the 2010 outbreak, in Greece. Results provide evidence of the implication of wild birds in a local enzootic cycle that could allow maintenance and amplification of the virus before and during the outbreak. Findings of past exposure of migratory birds to WNV upon their arrival in Greece during autumn migration, suggest avian species with similar migration traits as candidates for the introduction of WNV into Greece. The possibility that an endemic circulation of WNV could have caused the outbreak, after an amplification cycle due to favorable conditions cannot be excluded.
Metabonomic analysis of water extracts from Chinese and American ginsengs by 1H nuclear magnetic resonance: identification of chemical profile for quality control
Authors: Chan Pui Hei , Zheng Ken YZ , Tsim Karl WK , Lam Henry
Published: November 2012

Background

With the gaining popularity of commercially prepared decoctions of herbal medicines on the market, an objective and efficient way to reveal the authenticity of such products is urgently needed. Previous attempts to use chromatographic or spectroscopic methods to identify ginseng samples made use of components derived from methanol extracts of the herb. It was not established that these herbs can be distinguished solely from consumable components, which are responsible for the clinical efficacy of the herb.

In this study, metabonomics, or metabolic profiling, based on the application of 1H-Nuclear Magnetic Resonance (NMR), is applied to distinguish the water extracts of three closely related ginseng species: P. ginseng (from two different cultivated regions in China), P. notoginseng and P. quinquefolius.

Methods

A water extraction protocol that mimics how ginseng decoctions are made for consumption was used to prepare triplicate samples from each herb for analysis. High-resolution 1H NMR spectroscopy was used to acquire metabolic profiles of the four ginseng samples. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were able to distinguish different types of ginseng.

Results

H NMR metabolic profiling was performed to distinguish the water extracts of P. ginseng cultivated in Hebei and Jilin of China, both of which were distinguished from extracts of P. notoginseng and P. quinquefolius, by unsupervised principle component analysis based on the entire 1H NMR spectral fingerprint Statistically significant differences were found for several discriminating features traced to common metabolites and the ginsenosides Rg1 and Rd, in the 1H NMR spectra.

Conclusion

This study demonstrated that 1H NMR metabonomics can simultaneously distinguish different ginseng species and multiple samples of the same species that were cultivated in different regions. This technique is applicable to the authentication and quality control of ginseng products.
Use of response surface methodology for development of new microwell-based spectrophotometric method for determination of atrovastatin calcium in tablets
Authors: Wani Tanveer A , Ahmad Ajaz , Zargar Seema , Khalil Nasr Y , Darwish Ibrahim A
Published: November 2012

Background

Response surface methodology by Box–Behnken design employing the multivariate approach enables substantial improvement in the method development using fewer experiments, without wastage of large volumes of organic solvents, which leads to high analysis cost. This methodology has not been employed for development of a method for analysis of atorvastatin calcium (ATR-Ca).

Results

The present research study describes the use of in optimization and validation of a new microwell-based UV-Visible spectrophotometric method of for determination of ATR-Ca in its tablets. By the use of quadratic regression analysis, equations were developed to describe the behavior of the response as simultaneous functions of the selected independent variables. Accordingly, the optimum conditions were determined which included concentration of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), time of reaction and temperature. The absorbance of the colored-CT complex was measured at 460 nm by microwell-plate absorbance reader. The method was validated, in accordance with ICH guidelines for accuracy, precision, selectivity and linearity (r² = 0.9993) over the concentration range of 20–200 μg/ml. The assay was successfully applied to the analysis of ATR-Ca in its pharmaceutical dosage forms with good accuracy and precision.

Conclusion

The assay described herein has great practical value in the routine analysis of ATR-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, environmentally friendly "Green" approach) and reduction in the analysis cost by 50-fold.
Molecular confirmation of the occurrence in Germany of Anopheles daciae (Diptera, Culicidae)
Authors: Kronefeld Mandy , Dittmann Marko , Zielke Dorothee , Werner Doreen , Kampen Helge
Published: November 2012

Background

Anopheles daciae, a newly described member of the Maculipennis group, was recently reported from western, southern and eastern Europe. Before its recognition, it had commonly been listed under the name of An. messeae, due to its extreme morphological and genetic similarities. As the sibling species of the Maculipennis group are known to differ in their vector competences for malaria parasites and other pathogens, the occurrence of An. daciae in a given region might have an impact on the epidemiology of mosquito-borne diseases. Mosquito collections from different localities in Germany were therefore screened for An. daciae.

Methods

Adult and immature Maculipennis group mosquitoes were collected between May 2011 and June 2012 at 23 different sites in eight federal states of Germany. A standard PCR assay was used to differentiate the previously known sibling species while the ITS2 rDNA of specimens preliminarily identified as An. messeae/daciae was sequenced and analysed for species-specific nucleotide differences.

Results

Four hundred and seventy-seven Anopheles specimens were successively identified to Maculipennis group level by morphology and to species level by DNA-based methods. Four species of the Maculipennis group were registered: An. messeae (n = 384), An. maculipennis (n = 82), An. daciae (n = 10) and An. atroparvus (n = 1). Anopheles daciae occurred at four sites in three federal states of Germany, three of the sites being located in north-eastern Germany (federal states of Brandenburg and Saxony) while one collection site was situated in the northern Upper Rhine Valley in the federal state of Hesse, south-western Germany.

Conclusions

The detection of An. daciae represents the first recognition of this species in Germany where it was found to occur in sympatry with An. messeae and An. maculipennis. As the collection sites were in both north-eastern and south-western parts of Germany, the species is probably even more widely distributed in Germany than demonstrated, albeit apparently with low population densities. Research is needed that confirms the species status of An. daciae and elucidates its vector competence as compared to An. messeae and the other species of the Maculipennis group, in order to optimize management of possible future outbreaks of diseases caused by pathogen transmission through Maculipennis group mosquitoes.
Mitochondrial peroxidase TPx-2 is not essential in the blood and insect stages of Plasmodium berghei
Authors: Masuda-Suganuma Hirono , Usui Miho , Fukumoto Shinya , Inoue Noboru , Kawazu Shin-ichiro
Published: November 2012

Background

Malaria parasites actively proliferate in the body of their vertebrate and insect hosts, and are subjected to the toxic effects of reactive oxygen species. The antioxidant defenses of malaria parasites are considered to play essential roles in their survival and are thus considered promising targets for intervention. We sought to identify the cellular function of thioredoxin peroxidase-2 (TPx-2), which is expressed in the mitochondria, by disrupting the TPx-2 gene (pbtpx-2) of the rodent malaria parasite Plasmodium berghei.

Findings

In three independent experiments, two disruptant populations (TPx-2 KO) and three wild-type parasite populations with pyrimethamine resistance (dhfr-ts/mt at the DHFR-TS locus) and intact pbtpx-2 (TPx-2 WT) were obtained and cloned. Null expression of TPx-2 in the KO population was confirmed by RT-PCR and Western blot analyses. The TPx-2 KO parasite developed normally in mouse erythrocytes and multiplied at a rate similar to that of the TPx-2 WT parasite during the experimental period. The peak period of gametocytemia was delayed by 1 day in the TPx-2 KO compared with that of the TPx-2 WT and the parent parasite, however, the highest gametocyte number was comparable. The number of midgut oocysts in the TPx-2 KO at 14 days post feeding was comparable to that of the TPx-2 WT.

Conclusions

The present finding suggests that mitochondrial Prx TPx-2 is not essential for asexual and the insect stage development of the malaria parasite.
Exploiting the noise: improving biomarkers with ensembles of data analysis methodologies
Authors: Starmans Maud HW , Pintilie Melania , John Thomas , Der Sandy D , Shepherd Frances A , Jurisica Igor , Lambin Philippe , Tsao Ming-Sound , Boutros Paul C
Published: November 2012

Background

The advent of personalized medicine requires robust, reproducible biomarkers that indicate which treatment will maximize therapeutic benefit while minimizing side effects and costs. Numerous molecular signatures have been developed over the past decade to fill this need, but their validation and up-take into clinical settings has been poor. Here, we investigate the technical reasons underlying reported failures in biomarker validation for non-small cell lung cancer (NSCLC).

Methods

We evaluated two published prognostic multi-gene biomarkers for NSCLC in an independent 442-patient dataset. We then systematically assessed how technical factors influenced validation success.

Results

Both biomarkers validated successfully (biomarker #1: hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.21 to 2.19, P = 0.001; biomarker #2: HR 1.42, 95% CI 1.03 to 1.96, P = 0.030). Further, despite being underpowered for stage-specific analyses, both biomarkers successfully stratified stage II patients and biomarker #1 also stratified stage IB patients. We then systematically evaluated reasons for reported validation failures and find they can be directly attributed to technical challenges in data analysis. By examining 24 separate pre-processing techniques we show that minor alterations in pre-processing can change a successful prognostic biomarker (HR 1.85, 95% CI 1.37 to 2.50, P < 0.001) into one indistinguishable from random chance (HR 1.15, 95% CI 0.86 to 1.54, P = 0.348). Finally, we develop a new method, based on ensembles of analysis methodologies, to exploit this technical variability to improve biomarker robustness and to provide an independent confidence metric.

Conclusions

Biomarkers comprise a fundamental component of personalized medicine. We first validated two NSCLC prognostic biomarkers in an independent patient cohort. Power analyses demonstrate that even this large, 442-patient cohort is under-powered for stage-specific analyses. We then use these results to discover an unexpected sensitivity of validation to subtle data analysis decisions. Finally, we develop a novel algorithmic approach to exploit this sensitivity to improve biomarker robustness.
Increased information on waterborne outbreaks through efficient notification system enforces actions towards safe drinking water
Authors: Zacheus Outi , Miettinen Ilkka T.
Published: November 2012

In 1997, a compulsory notification system for waterborne outbreaks was introduced in Finland. The main aim of this notification is to obtain immediate information on suspected waterborne outbreaks in order to restrict and manage the outbreak promptly. During the past ten years, there have been 67 waterborne outbreaks in Finland, mainly associated with small groundwater supplies or private wells. The number of reported waterborne outbreaks has increased since the launch of the notification system indicating that the threshold limit of outbreak detection has most probably decreased. The number of cases of illness has fulfilled the national health target, which is below 0.01% of the population, but more action is still needed to ensure the production of safe drinking water under all circumstances. Ten years accumulation of knowledge on outbreaks has revealed that a compulsory notification system is an effective tool to gather information on waterborne outbreaks. The system has also increased awareness of possible problems related to the quality of drinking water. This article summarises management and legislative actions and policy measures taken so far in Finland to reduce the number of outbreaks and cases of illness related to them.
National surveillance capacity of water-related diseases in the WHO European Region
Authors: Blasi M. , Carere M. , Funari E.
Published: November 2012

Water-related diseases continue to cause a high burden of mortality and morbidity in the countries of the European Region. Parties to the Protocol on Water and Health are committed to the sustainable use of water resources, the provision of safe drinking water and adequate sanitation to all people of the European Region, and to the reduction of the burden of water-related diseases. A specialized Task Force is implementing a work plan aimed at strengthening the capacity for water-related disease surveillance, outbreak detection and contingency planning. Parties to the Protocol are obliged to set targets, and report on progress on water-related disease surveillance. The present paper aims to provide a baseline assessment of national capacities for water-related disease surveillance on the basis of the replies to a questionnaire. This was prepared in English and Russian and administered to 53 countries, 15 of which replied. The results confirm the heterogeneity in surveillance systems, the weakness of many countries to adequately survey emerging water-related diseases, and the need for specific remedial action. The findings of the exercise will form the basis for future action under the Protocol on Water and Health.
Culture-based indicators of fecal contamination and molecular microbial indicators rarely correlate with Campylobacter spp. in recreational waters
Authors: Hellein Kristen N. , Battie Cynthia , Tauchman Eric , Lund Deanna , Oyarzabal Omar A. , Lepo Joe Eugene
Published: November 2012

Campylobacter spp. are the leading cause of gastroenteritis worldwide. Most human infections result from contaminated food; however, infections are also caused by recreational waterway contamination. Campylobacter culture is technically challenging and enumeration by culture-based methods is onerous. Thus, we employed qPCR to quantify Campylobacter spp. in fresh- and marine-water samples, raw sewage and animal feces. Multiplex PCR determined whether Campylobacter jejuni or C. coli, most commonly associated with human disease, were present in qPCR-positive samples. Campylobacters were detected in raw sewage, and in feces of all avian and mammalian species tested. Campylobacter-positive concentrations ranged from 68 to 2.3 × 106 cells per 500 mL. Although C. jejuni and C. coli were rare in waterways, they were prevalent in sewage and feces. Campylobacter-specific qPCR screening of environmental waters did not correlate with the regulatory EPA method 1600 (Enterococcus culture), nor with culture-independent, molecular-based microbial source tracking indicators, such as human polyomavirus, human Bacteroidales and Methanobrevibacter smithii. Our results suggest that neither the standard EPA method nor the newly proposed culture-independent methods are appropriate surrogates for Campylobacter contamination in water. Thus, assays for specific pathogens may be necessary to protect human health, especially in waters that are contaminated with sewage and animal feces.
Occurrence of Aeromonas spp. in a random sample of drinking water distribution systems in the USA
Authors: Egorov Andrey I. , Best Jennifer M. Birkenhauer , Frebis Christopher P. , Karapondo Michella S.
Published: November 2012

Aeromonads are aquatic bacteria found in drinking water supplies worldwide. Some species, such as Aeromonas hydrophila, can cause disease in humans. For this survey, 293 United States public water systems were selected using random sampling, stratified by water source and system type. Water samples were collected during one year from three sites (six samples per site) in each system. Temperature, pH, turbidity, total and free chlorine were measured using standard methods. Aeromonads were detected in 130 of 5,042 valid samples (2.6%) from 42 (14.3%) systems using the ampicillin-dextrin agar with vancomycin culture method with oxidase, trehalose and indole confirmation tests. Concentrations of aeromonads in positive samples were 0.2 to 880 (median 1.6) colony-forming units (CFU) per 100 mL. Adjusted odds ratios of Aeromonas detection were 1.6 (95% confidence limits 1.0, 2.5) during the summer season, 3.3 (1.8, 6.2) for turbidity above 0.5 nephelometric units and 9.1 (3.5, 24) at 0 mg/L compared with 0.25 mg/L total chlorine. Geographic region, system size and type of water source were not significant predictors of Aeromonas detection in multivariate regression analysis. The results of this survey demonstrate the importance of maintaining adequate residual chlorine and low turbidity for preventing drinking water contamination with aeromonads.
Water and sanitation issues for persons with disabilities in low- and middle-income countries: a literature review and discussion of implications for global health and international development
Authors: Groce N. , Bailey N. , Lang R. , Trani J. F. , Kett M.
Published: November 2012

The critical importance of unrestricted access to clean drinking water and basic sanitation for all is highlighted in Millennium Development Goal 7, which calls for the reduction by half of the proportion of people without such access by 2015. Unfortunately, little attention has been paid to the needs of such access for the one billion people living with a disability worldwide, despite the fact that the right to equal access for all international development initiatives is guaranteed in the new United Nations Convention on the Rights of Persons with Disabilities. In this paper, we review what is currently known about access to water and sanitation for persons with disabilities in low- and middle-income countries from the perspective of both international development and global health, and identify existing gaps in research, practice and policy that are of pressing concern if the water and sanitation needs of this large – and largely overlooked – population are to be addressed.
Environmental water governance in federal rivers: opportunities and limits for subsidiarity in Australia's Murray–Darling River
Authors: Garrick Dustin , Bark Rosalind , Connor Jeff , Banerjee Onil
Published: November 2012

A reform process is underway in the Murray–Darling Basin (Australia) to reallocate water from irrigated agriculture to the environment. The scale, complexity and politics of the recovery process have prompted interest in the role of local environmental water managers within state and federal governance arrangements. This paper examines prospects for a local role in environmental water management through the lens of the subsidiarity principle: the notion that effective governance devolves tasks to the lowest level with the political authority and capacity to perform them. The article defines and applies the subsidiarity principle to assess evolving federal–state–local interactions in environmental water policy, planning and practice in Australia's Murray–Darling River. In this context, subsidiarity is useful to clarify institutional roles and their coordination at a whole-of-river level. This analysis demonstrates opportunities for a local role in information gathering, innovation and operational flexibility to respond to opportunities in real time. It identifies significant limits to local action in upstream–downstream tradeoffs, economies of scale, capacity building and cost sharing for basin-wide or national interests, and accountability mechanisms to balance local, state and national rights and responsibilities. Lessons are relevant internationally for regions confronting complex allocation tradeoffs between human and environmental needs within multi-jurisdictional federal systems.
Computational Tools for Genome-Wide miRNA Prediction and Study
Authors: B. Malas Tareq , Ravasi Timothy
Published: November 2012

MicroRNAs (miRNAs) are single-stranded non-coding RNA susually of 22 nucleotidesin length that play an
important post-transcriptional regulation role in many organisms. MicroRNAs bind a seed sequence to the 3'-untranslated
region (UTR) region of the target messenger RNA (mRNA), inducing degradation or inhibition of translation and
resulting in a reduction in the protein level. This regulatory mechanism is central to many biological processes and
perturbation could lead to diseases such as cancer. Given the biological importance, of miRNAs, there is a great need to
identify and study their targets and functions. However, miRNAs are very difficult to clone in the lab and this has
hindered the identification of novel miRNAs. Next-generation sequencing coupled with new computational tools has
recently evolved to help researchers efficiently identify large numbers of novel miRNAs. In this review, we describe
recent miRNA prediction tools and discuss their priorities, advantages and disadvantages.
Post-Traumatic Malunion of the Proximal Phalanx of the Finger. Medium-Term Results in 24 Cases Treated by “In Situ” Osteotomy
Authors: Potenza Vito , De Luna Vincenzo , Maglione Pierluigi , Garro Luca , Farsetti Pasquale , Roberto Caterini
Published: November 2012

We report the clinical and radiographic medium-term results obtained for 20 patients (24 fingers) treated surgically for post-traumatic malunion of the proximal phalanx of the finger. In all cases we performed a corrective osteoclasia or osteotomy at the site of malunion, followed by miniplate and screw fixation or by screw fixation only. The corrective osteoclasia was performed when malalignment was addressed within six weeks after injury. Two patients who had two fractures underwent additional surgery (tenolysis and/or capsulolysis) to improve function and ROM. At the final follow-up, at a mean of 24 months after corrective surgery, good or excellent clinical and radiographic results were obtained in all the patients. The pseudoclaw deformity disappeared in all cases in which a volar angulation deformity was present. An average improvement of about 30% in the range of motion of the MP and PIP joints was observed; only 4 patients complained of mild pain at the maximum degrees of articular excursion of the MP and PIP joints. All the patients presented an improvement in grip strength. The mean DASH score in our series was 5 points. In two of the four cases treated by an intra-articular corrective osteotomy, mild radiographic signs of osteoarthritis at the MP joint were present. The data for this study confirm that “in situ” osteotomy stabilized by miniplates and/or screws is an effective procedure to correct post-traumatic malunions of the proximal phalanges of the fingers.
Editorial
Authors: Mom Gijs , Seiler Cotten , Clarsen Georgine
Published: November 2012

This issue is the last of volume 2. With this, we have reached a milestone in our fledgling history and a threshold to the last volume in our series of three in which we have strived, and still strive, to get all the important elements of a good journal in place. According to our original plans our priorities were to establish top-quality submissions, a splendid pool of knowledgeable and rigorous but generous transdisciplinary referees, efficient refereeing procedures, satisfactory rejection rates, timely manuscript production, and a subscriber base that crosses disciplinary boundaries. Although quantitatively not yet up to standard, our readership is variegated and adventurous enough to appreciate our desire to “rethink mobility” and dedicate printed space to “mobility writ large.” Before we begin to produce volume 3 (2012) this September, our editorial team will retreat, evaluate, and look each other in the eyes to determine what we can do better.
Modern Mobilities in Mainland China
Authors: Kim Nanny , Tao Xu
Published: November 2012

Modern transport history in China is rooted in academic support of the modernization effort. Influential and creative historians of the Republican period (1911–1949) reformulated “mobility history” (交通史) as an academic discipline. Its approaches were inspired by Western historical method as well as sociology and ethnology, but retained the tradition of an erudite consideration of all written texts as potential sources. From the 1950s, however, the field became a rarely visited sideline of history. With the restoration and vigorous expansion of academic research since the 1980s, transport and mobility gradually reemerged as a key interest among historians. By the turn of the century, the number of scholars working in this subdiscipline approached critical mass. In 2009, a group of historians working on railroads founded the Association for the History of Modern Chinese Mobility and Society (中国近代交通社会史研究学会). Jiang Pei 江沛 of Nankai University, Tianjin, was the initiator of the association and organized the first meeting. The second meeting, in 2011, was organized by Ding Xianyong 丁贤勇 of Hangzhou Normal University. The third meeting in fall 2012 will be hosted by Fudan University, Shanghai. The following is a brief survey of the field of mobility studies in mainland China, aiming not for exhaustive completeness but for an introduction to non-Chinese-speaking colleagues.
Mobility, Interrupted
Authors: Breen Deborah
Published: November 2012

Sherlock Holmes: A Game of Shadows (UK and USA, 2011, Warner Bros. Pictures, Directed by Guy Ritchie. Screenplay Kieran Mulroney and Michele Mulroney. With Robert Downey Jr., Jude Law, Jared Harris, Noomi Rapace).
Looking Beyond Facile Understandings of ‘Literalness’ in Music–Dance Collaborations: Mark Morris's All Fours
Authors: Robb Hamish J.
Published: November 2012

Notions of ‘visualisation’ or ‘literalness’ in discussions of dance-music collaborations mistakenly imply that dance is able to map completely onto music, and that such dancing says nothing new. Given the complexities involved in meaning formation through gesture, there is an endless number of ways to sympathetically choreograph the same musical phrase, just as there are numerous ways to interpret a single physical gesture. Through an analysis of Mark Morris's All Fours, a choreography set to Bartók's Fourth String Quartet, I offer an opposing view to those detractors of Morris who claim that his work is ‘overly literal’. I argue that Morris's sensitive choreography provides us with the missing link between the characters and emotions projected through Bartók's music on the one hand, and the very precise and less audible compositional techniques on the other. Furthermore, I demonstrate how Morris's carefully planned choreographic choices, repetitive mappings, and gestural tropes (the juxtaposition of two seemingly contradictory gestures) provide the means for highly imaginative and complex narratives, one of which I offer here. Thus, I illustrate how dance gestures that may initially seem to simply ‘mimic’ the music actually perform larger roles in the formation of networks of meaning.