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1.
Dany Morisset Petra Kralj Novak Darko Zupani? Kristina Gruden Nada Lavra? Jana ?el 《BMC bioinformatics》2014,15(1)
Background
With the increasing pace of new Genetically Modified Organisms (GMOs) authorized or in pipeline for commercialization worldwide, the task of the laboratories in charge to test the compliance of food, feed or seed samples with their relevant regulations became difficult and costly. Many of them have already adopted the so called "matrix approach" to rationalize the resources and efforts used to increase their efficiency within a limited budget. Most of the time, the "matrix approach" is implemented using limited information and some proprietary (if any) computational tool to efficiently use the available data.Results
The developed GMOseek software is designed to support decision making in all the phases of routine GMO laboratory testing, including the interpretation of wet-lab results. The tool makes use of a tabulated matrix of GM events and their genetic elements, of the laboratory analysis history and the available information about the sample at hand. The tool uses an optimization approach to suggest the most suited screening assays for the given sample. The practical GMOseek user interface allows the user to customize the search for a cost-efficient combination of screening assays to be employed on a given sample. It further guides the user to select appropriate analyses to determine the presence of individual GM events in the analyzed sample, and it helps taking a final decision regarding the GMO composition in the sample. GMOseek can also be used to evaluate new, previously unused GMO screening targets and to estimate the profitability of developing new GMO screening methods.Conclusion
The presented freely available software tool offers the GMO testing laboratories the possibility to select combinations of assays (e.g. quantitative real-time PCR tests) needed for their task, by allowing the expert to express his/her preferences in terms of multiplexing and cost. The utility of GMOseek is exemplified by analyzing selected food, feed and seed samples from a national reference laboratory for GMO testing and by comparing its performance to existing tools which use the matrix approach. GMOseek proves superior when tested on real samples in terms of GMO coverage and cost efficiency of its screening strategies, including its capacity of simple interpretation of the testing results.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-258) contains supplementary material, which is available to authorized users. 相似文献2.
3.
Backgrounds and Aims
Conceptual and terminological conflicts in inflorescence morphology indicate a lack of understanding of the phenotypic diversity of inflorescences. In this study, an ontogeny-based inflorescence concept is presented considering different meristem types and developmental pathways. By going back to the ontogenetic origin, diversity is reduced to a limited number of types and terms.Methods
Species from 105 genera in 52 angiosperm families are investigated to identify their specific reproductive meristems and developmental pathways. Based on these studies, long-term experience with inflorescences and literature research, a conceptual framework for the understanding of inflorescences is presented.Key Results
Ontogeny reveals that reproductive systems traditionally called inflorescences fall into three groups, i.e. ‘flowering shoot systems’ (FSS), ‘inflorescences’ sensu stricto and ‘floral units’ (FUs). Our concept is, first, based on the identification of reproductive meristem position and developmental potential. The FSS, defined as a seasonal growth unit, is used as a reference framework. As the FSS is a leafy shoot system bearing reproductive units, foliage and flowering sequence play an important role. Second, the identification of two different flower-producing meristems is essential. While ‘inflorescence meristems’ (IMs) share acropetal primordia production with vegetative meristems, ‘floral unit meristems’ (FUMs) resemble flower meristems in being indeterminate. IMs produce the basic inflorescence types, i.e. compound and simple racemes, panicles and botryoids. FUMs give rise to dense, often flower-like units (e.g. heads). They occur solitarily at the FSS or occupy flower positions in inflorescences, rendering the latter thyrses in the case of cymose branching.Conclusions
The ontogenetic concept differs from all existing inflorescence concepts in being based on meristems and developmental processes. It includes clear terms and allows homology statements. Transitional forms are an explicit part of the concept, illustrating the ontogenetic potential for character transformation in evolution. 相似文献4.
There is a need for effective interventions and policies that target the leading preventable causes of death in the U.S. (e.g., smoking, overweight/obesity, physical inactivity). Such efforts could be aided by the use of publicly available, real-time search query data that illustrate times and locations of high and low public interest in behaviors related to preventable causes of death.
Objectives
This study explored patterns of search query activity for the terms ‘weight’, ‘diet’, ‘fitness’, and ‘smoking’ using Google Insights for Search.Methods
Search activity for ‘weight’, ‘diet’, ‘fitness’, and ‘smoking’ conducted within the United States via Google between January 4th, 2004 (first date data was available) and November 28th, 2011 (date of data download and analysis) were analyzed. Using a generalized linear model, we explored the effects of time (month) on mean relative search volume for all four terms.Results
Models suggest a significant effect of month on mean search volume for all four terms. Search activity for all four terms was highest in January with observable declines throughout the remainder of the year.Conclusions
These findings demonstrate discernable temporal patterns of search activity for four areas of behavior change. These findings could be used to inform the timing, location and messaging of interventions, campaigns and policies targeting these behaviors. 相似文献5.
Lee R. Ferguson Sandeep Grover James M. Dominguez II Sankarathi Balaiya Kakarla V. Chalam 《PloS one》2014,9(10)
Background
This study determines ‘correlation constants’ between the gold standard histological measurement of retinal thickness and the newer spectral-domain optical coherence tomography (SD-OCT) technology in adult C57BL/6 mice.Methods
Forty-eight eyes from adult mice underwent SD-OCT imaging and then were histologically prepared for frozen sectioning with H&E staining. Retinal thickness was measured via 10x light microscopy. SD-OCT images and histological sections were standardized to three anatomical sites relative to the optic nerve head (ONH) location. The ratios between SD-OCT to histological thickness for total retinal thickness (TRT) and six sublayers were defined as ‘correlation constants’.Results
Mean (± SE) TRT for SD-OCT and histological sections was 210.95 µm (±1.09) and 219.58 µm (±2.67), respectively. The mean ‘correlation constant’ for TRT between the SD-OCT and histological sections was 0.96. The retinal thickness for all sublayers measured by SD-OCT vs. histology were also similar, the ‘correlation constant’ values ranged from 0.70 to 1.17. All SD-OCT and histological measurements demonstrated highly significant (p<0.01) strong positive correlations.Conclusion
This study establishes conversion factors for the translation of ex vivo data into in vivo information; thus enhancing the applicability of SD-OCT in translational research. 相似文献6.
7.
Objective
To test the ‘Liverpool Osteoarthritis in Dogs’ (LOAD) questionnaire for construct and criterion validity, and to similarly test the Helsinki Chronic Pain Index (HCPI) and the Canine Brief Pain Inventory (CBPI).Design
Prospective Study.Animals
222 dogs with osteoarthritis.Procedure
Osteoarthritis was diagnosed in a cohort of dogs on the basis of clinical history and orthopedic examination. Force-platform analysis was performed and a “symmetry index” for peak vertical force (PVF) was calculated. Owners completed LOAD, CBPI and HCPI instruments. As a test of construct validity, inter-instrument correlations were calculated. As a test of criterion validity, the correlations between instrument scores and PVF symmetry scores were calculated. Additionally, internal consistency of all instruments was calculated and compared to those previously reported. Factor analysis is reported for the first time for LOAD, and is compared to that previously reported for CBPI and HCPI.Results
Significant moderate correlations were found between all instruments, implying construct validity for all instruments. Significant weak correlations were found between LOAD scores and PVF symmetry index, and between CBPI scores and PVF symmetry index.Conclusion and Clinical Relevance
LOAD is an owner-completed clinical metrology instrument that can be recommended for the measurement of canine osteoarthritis. It is convenient to use, validated and, as demonstrated here for the first time, has a correlation with force-platform data. 相似文献8.
Background
Pervasive negative thoughts about the self are central to the experience of depression. Brain imaging studies in the general population have localised self-related cognitive processing to areas of the medial pre-frontal cortex.Aims
To use fMRI to compare the neural correlates of self-referential processing in depressed and non-depressed participants.Method
Cross-sectional comparison of regional activation using Blood Oxygen Level Dependent (BOLD) fMRI in 13 non-medicated participants with major depressive episode and 14 comparison participants, whilst carrying out a self-referential cognitive task.Results
Both groups showed significant activation of the dorsomedial pre-frontal cortex and posterior cingulate cortex in the ‘self-referent’ condition. The depressed group showed significantly greater activation in the medial superior frontal cortex during the self-referent task. No difference was observed between groups in the ‘other-referent’ condition.Conclusions
Major depressive episode is associated with specific neurofunctional changes related to self-referential processing. 相似文献9.
Jun'ya Takakura Takayuki Nishimura Shigeki Watanuki 《Journal of physiological anthropology》2013,32(1):26
Background
Human core body temperature is kept quasi-constant regardless of varying thermal environments. It is well known that physiological thermoregulatory systems are under the control of central and peripheral sensory organs that are sensitive to thermal energy. If these systems wrongly respond to non-thermal stimuli, it may disturb human homeostasis.Methods
Fifteen participants viewed video images evoking hot or cold impressions in a thermally constant environment. Cardiovascular indices were recorded during the experiments. Correlations between the ‘hot-cold’ impression scores and cardiovascular indices were calculated.Results
The changes of heart rate, cardiac output, and total peripheral resistance were significantly correlated with the ‘hot-cold’ impression scores, and the tendencies were similar to those in actual thermal environments corresponding to the impressions.Conclusions
The present results suggest that visual information without any thermal energy can affect physiological thermoregulatory systems at least superficially. To avoid such ‘virtual’ environments disturbing human homeostasis, further study and more attention are needed. 相似文献10.
Natalie V. S. Vinkeles Melchers Govert J. van Dam David Shaproski Anthony I. Kahama Eric A. T. Brienen Birgitte J. Vennervald Lisette van Lieshout 《PLoS neglected tropical diseases》2014,8(4)
Background
In an effort to enhance accuracy of diagnosis of Schistosoma haematobium, this study explores day-to-day variability and diagnostic performance of real-time PCR for detection and quantification of Schistosoma DNA compared to other diagnostic tools in an endemic area before and after treatment.Methodology
Previously collected urine samples (N = 390) from 114 preselected proven parasitological and/or clinical S. haematobium positive Kenyan schoolchildren were analyzed by a Schistosoma internal transcribed spacer-based real-time PCR after 14 years of storage. Pre-treatment day-to-day fluctuations of PCR and microscopy over three consecutive days were measured for 24 children using intra-class correlation coefficient. A combined ‘gold standard’ (PCR and/or microscopy positive) was used to measure sensitivity and negative predictive value (NPV) of several diagnostic tools at baseline, two and 18 months post-treatment with praziquantel.Principal Findings
All 24 repeatedly tested children were PCR-positive over three days with little daily variation in median Ct-values, while 83.3% were found to be egg-positive for S. haematobium at day 1 and 75.0% at day 2 and 3 pre-treatment, signifying daily fluctuations in microscopy diagnosis. Of all 114 preselected schoolchildren, repeated microscopic measurements were required to detect 96.5% versus 100% of positive pre-treatment cases by single PCR. At two months post-treatment, microscopy and PCR detected 22.8% versus 69.3% positive children, respectively. Based on the ‘gold standard’, PCR showed high sensitivity (>92%) as compared to >31% sensitivity for microscopy, both pre- and post-treatment.Conclusions/Significance
Detection and quantification of Schistosoma DNA in urine by real-time PCR was shown to be a powerful and specific diagnostic tool for detection of S. haematobium infections, with less day-to-day variation and higher sensitivity compared to microscopy. The superior performance of PCR before, and two and 18 months post-treatment provides a compelling argument for PCR as an accurate and reproducible tool for monitoring treatment efficacy. 相似文献11.
Marlies T. van Dalen Jacqueline J. Suijker Janet MacNeil-Vroomen Marjon van Rijn Eric P. Moll van Charante Sophia E. de Rooij Bianca M. Buurman 《PloS one》2014,9(4)
Background
Self-reported data are often used for estimates on healthcare utilization in cost-effectiveness studies.Objective
To analyze older adults’ self-report of healthcare utilization compared to data obtained from the general practitioners’ (GP) electronic medical record (EMR) and to study the differences in healthcare utilization between those who completed the study, those who did not respond, and those lost to follow-up.Methods
A prospective cohort study was conducted among community-dwelling persons aged 70 years and above, without dementia and not living in a nursing home. Self-reporting questionnaires were compared to healthcare utilization data extracted from the EMR at the GP-office.Results
Overall, 790 persons completed questionnaires at baseline, median age 75 years (IQR 72–80), 55.8% had no disabilities in (instrumental) activities of daily living. Correlations between self-report data and EMR data on healthcare utilization were substantial for ‘hospitalizations’ and ‘GP home visits’ at 12 months intraclass correlation coefficient 0.63 (95% CI; 0.58–0.68). Compared to the EMR, self-reported healthcare utilization was generally slightly over-reported. Non-respondents received more GP home visits (p<0.05). Of the participants who died or were institutionalized 62.2% received 2 or more home visits (p<0.001) and 18.9% had 2 or more hospital admissions (p<0.001) versus respectively 18.6% and 3.9% of the participants who completed the study. Of the participants lost to follow-up for other reasons 33.0% received 2 or more home visits (p<0.01) versus 18.6 of the participants who completed the study.Conclusions
Self-report of hospitalizations and GP home visits in a broadly ‘healthy’ community-dwelling older population seems adequate and efficient. However, as people become older and more functionally impaired, collecting healthcare utilization data from the EMR should be considered to avoid measurement bias, particularly if the data will be used to support economic evaluation. 相似文献12.
Jeremy Howick Felicity L. Bishop Carl Heneghan Jane Wolstenholme Sarah Stevens F. D. Richard Hobbs George Lewith 《PloS one》2013,8(3)
Objectives
Surveys in various countries suggest 17% to 80% of doctors prescribe ‘placebos’ in routine practice, but prevalence of placebo use in UK primary care is unknown.Methods
We administered a web-based questionnaire to a representative sample of UK general practitioners. Following surveys conducted in other countries we divided placebos into ‘pure’ and ‘impure’. ‘Impure’ placebos are interventions with clear efficacy for certain conditions but are prescribed for ailments where their efficacy is unknown, such as antibiotics for suspected viral infections. ‘Pure’ placebos are interventions such as sugar pills or saline injections without direct pharmacologically active ingredients for the condition being treated. We initiated the survey in April 2012. Two reminders were sent and electronic data collection closed after 4 weeks.Results
We surveyed 1715 general practitioners and 783 (46%) completed our questionnaire. Our respondents were similar to those of all registered UK doctors suggesting our results are generalizable. 12% (95% CI 10 to 15) of respondents used pure placebos while 97% (95% CI 96 to 98) used impure placebos at least once in their career. 1% of respondents used pure placebos, and 77% (95% CI 74 to 79) used impure placebos at least once per week. Most (66% for pure, 84% for impure) respondents stated placebos were ethical in some circumstances.Conclusion and implications
Placebo use is common in primary care but questions remain about their benefits, harms, costs, and whether they can be delivered ethically. Further research is required to investigate ethically acceptable and cost-effective placebo interventions. 相似文献13.
Zumin Shi Baojun Yuan Gary A. Wittert Xiaoqun Pan Yue Dai Robert Adams Anne W. Taylor 《PloS one》2012,7(12)
Objectives
Emerging evidence shows that diet is related to asthma. The aim of this analysis was to investigate the association between monosodium glutamate (MSG) intake, overall dietary patterns and asthma.Methods
Data from 1486 Chinese men and women who participated in the Jiangsu Nutrition Study (JIN) were analyzed. In this study, MSG intake and dietary patterns were quantitatively assessed in 2002. Information on asthma history was collected during followed-up in 2007.Results
Of the sample, 1.4% reported ever having asthma. MSG intake was not positively associated with asthma. There was a significant positive association between ‘traditional’ (high loadings on rice, wheat flour, and vegetable) food pattern and asthma. No association between ’macho’ (rich in meat and alcohol), ‘sweet tooth’ (high loadings on cake, milk, and yoghurt) ‘vegetable rich’ (high loadings on whole grain, fruit, and vegetable) food patterns and asthma was found. Smoking and overweight were not associated with asthma in the sample.Conclusion
While a ‘Traditional’ food pattern was positively associated with asthma among Chinese adults, there was no significant association between MSG intake and asthma. 相似文献14.
Jin-young Min Kyung-jong Lee Jae-beom Park Sung-il Cho Shin-goo Park Kyoungbok Min 《PloS one》2012,7(10)
Background
We focused on whether changes in the occupational status of older male adults can be influenced by social engagement and health status measured at the baseline.Methods
This study used a sample of the Korean Longitudinal Study of Aging (KLoSA), and the study population was restricted to 1.531 men who were aged 55 to 80 years at the 2006 baseline survey and participated in the second survey in 2008. Social engagement and health status, measured by the number of chronic diseases, grip strength, and depressive symptoms as well as covariates (age, marital status, educational level, and household income) were based on data from the 2006 baseline survey. Occupational engagement over the first and second survey was divided into four categories: ‘consistently employed’ (n = 892), ‘employed-unemployed’ (n = 152), ‘unemployed-employed’ (n = 138), and ‘consistently unemployed’ (n = 349).Results
In the multinomial model, the ‘consistently employed’ and ‘unemployed-employed’ groups had significantly higher social engagement (1.19 and 1.32 times, respectively) than the referent. The number of chronic diseases was significantly associated with four occupational changes, and the ‘unemployed-employed’ had the fewest chronic conditions.Conclusion
Our finding suggests that social engagement and health status are likely to affect opportunities to continue working or to start working for older male adults. 相似文献15.
Esther J. Smits Antti J. Tolonen Luc Cluitmans Mark van Gils Bernard A. Conway Rutger C. Zietsma Klaus L. Leenders Natasha M. Maurits 《PloS one》2014,9(5)
Objective
To assess whether standardized handwriting can provide quantitative measures to distinguish patients diagnosed with Parkinson''s disease from age- and gender-matched healthy control participants.Design
Exploratory study. Pen tip trajectories were recorded during circle, spiral and line drawing and repeated character ‘elelelel’ and sentence writing, performed by Parkinson patients and healthy control participants. Parkinson patients were tested after overnight withdrawal of anti-Parkinsonian medication.Setting
University Medical Center Groningen, tertiary care, the Netherlands.Participants
Patients with Parkinson''s disease (n = 10; mean age 69.0 years; 6 male) and healthy controls (n = 10; mean age 68.1 years; 6 male).Interventions
Not applicable.Main Outcome Measures
Movement time and velocity to detect bradykinesia and the size of writing to detect micrographia. A rest recording to investigate the presence of a rest-tremor, by frequency analysis.Results
Mean disease duration in the Parkinson group was 4.4 years and the patients were in modified Hoehn-Yahr stages 1–2.5. In general, Parkinson patients were slower than healthy control participants. Median time per repetition, median velocity and median acceleration of the sentence task and median velocity of the elel task differed significantly between Parkinson patients and healthy control participants (all p<0.0014). Parkinson patients also wrote smaller than healthy control participants and the width of the ‘e’ in the elel task was significantly smaller in Parkinson patients compared to healthy control participants (p<0.0014). A rest-tremor was detected in the three patients who were clinically assessed as having rest-tremor.Conclusions
This study shows that standardized handwriting can provide objective measures for bradykinesia, tremor and micrographia to distinguish Parkinson patients from healthy control participants. 相似文献16.
Lynne M. Boddy Non E. Thomas Stuart J. Fairclough Keith Tolfrey Sinead Brophy Anwen Rees Gareth Knox Julien S. Baker Gareth Stratton 《PloS one》2012,7(9)
Objectives
1. to investigate whether 20 m multi-stage shuttle run performance (20mSRT), an indirect measure of aerobic fitness, could discriminate between healthy and overweight status in 9–10.9 yr old schoolchildren using Receiver Operating Characteristic (ROC) analysis; 2. Investigate if cardiometabolic risk differed by aerobic fitness group by applying the ROC cut point to a second, cross-sectional cohort.Design
Analysis of cross-sectional data.Participants
16,619 9–10.9 year old participants from SportsLinx project and 300 11–13.9 year old participants from the Welsh Schools Health and Fitness Study.Outcome Measures
SportsLinx; 20mSRT, body mass index (BMI), waist circumference, subscapular and superilliac skinfold thicknesses. Welsh Schools Health and Fitness Study; 20mSRT performance, waist circumference, and clustered cardiometabolic risk.Analyses
Three ROC curve analyses were completed, each using 20mSRT performance with ROC curve 1 related to BMI, curve 2 was related to waist circumference and 3 was related to skinfolds (estimated % body fat). These were repeated for both girls and boys. The mean of the three aerobic fitness thresholds was retained for analysis. The thresholds were subsequently applied to clustered cardiometabolic risk data from the Welsh Schools study to assess whether risk differed by aerobic fitness group.Results
The diagnostic accuracy of the ROC generated thresholds was higher than would be expected by chance (all models AUC >0.7). The mean thresholds were 33 and 25 shuttles for boys and girls respectively. Participants classified as ‘fit’ had significantly lower cardiometabolic risk scores in comparison to those classed as unfit (p<0.001).Conclusion
The use of the ROC generated cut points by health professionals, teachers and coaches may provide the opportunity to apply population level ‘risk identification and stratification’ processes and plan for “at-risk” children to be referred onto intervention services. 相似文献17.
Preciosa M. Coloma Martijn J. Schuemie Gianluca Trifirò Laura Furlong Erik van Mulligen Anna Bauer-Mehren Paul Avillach Jan Kors Ferran Sanz Jordi Mestres José Luis Oliveira Scott Boyer Ernst Ahlberg Helgee Mariam Molokhia Justin Matthews David Prieto-Merino Rosa Gini Ron Herings Giampiero Mazzaglia Gino Picelli Lorenza Scotti Lars Pedersen Johan van der Lei Miriam Sturkenboom 《PloS one》2013,8(8)
18.
Sabine Witt Reiner Leidl Christian Becker Rolf Holle Michael Block Johannes Brachmann Sigmund Silber Bj?rn Stollenwerk 《PloS one》2014,9(12)
Background
Cardiovascular disease is the leading cause of morbidity and mortality in the developed world. To reduce this burden of disease, a German sickness fund (‘Siemens-Betriebskrankenkasse’, SBK) initiated the prevention programme ‘KardioPro’ including primary (risk factor reduction) and secondary (screening) prevention and guideline-based treatment. The aim of this study was to assess the effectiveness of ‘KardioPro’ as it is implemented in the real world.Methods
The study is based on sickness fund routine data. The control group was selected from non-participants via propensity score matching. Study analysis was based on time-to-event analysis via Cox proportional hazards regression with the endpoint ‘all-cause mortality, acute myocardial infarction (MI) and ischemic stroke (1)’, ‘all-cause mortality (2)’ and ‘non-fatal acute MI and ischemic stroke (3)’.Results
A total of 26,202 insurants were included, 13,101 participants and 13,101 control subjects. ‘KardioPro’ enrolment was associated with risk reductions of 23.5% (95% confidence interval (CI) 13.0–32.7%) (1), 41.7% (95% CI 30.2–51.2%) (2) and 3.5% (hazard ratio 0.965, 95% CI 0.811–1.148) (3). This corresponds to an absolute risk reduction of 0.29% (1), 0.31% (2) and 0.03% (3) per year.Conclusion
The prevention programme initiated by a German statutory sickness fund appears to be effective with regard to all-cause mortality. The non-significant reduction in non-fatal events might result from a shift from fatal to non-fatal events. 相似文献19.
Background
Numerous studies have reported on the healing powers of plants and nature, but there have not been so many instances of experimental research. In particular, there are very few psychological and physiological studies using tactile stimuli. This study examines the psychological and physiological effects of touching plant foliage by using an evaluation profile of the subjects’ impressions and investigating cerebral blood flow.Methods
The subjects were 14 young Japanese men aged from 21 to 27 years (mean ± standard deviation: 23.6 ± 2.4). With their eyes closed, the subjects touched four different tactile samples including a leaf of natural pothos (Epipremnum aureum). The physiological indices were compared before and after each stimulus. Psychological indices were obtained using a ‘semantic differential’ method.Results
The fabric stimulus gave people ‘soft’ and ‘rough’ impressions, ‘kind’, ‘peaceful’ and ‘pleasant’ feelings psychologically, and a sense of physiological calm. On the other hand, the metal stimulus gave people ‘cold’, ‘smooth’ and ‘hard’ impressions and an image of something ‘artificial’. The metal stimulus caused a stress response in human cerebral blood flow although its evaluation in terms of ‘pleasant or unpleasant’ was neutral. There were no remarkable differences between the stimuli of natural and artificial pothos compared with other types of stimulus psychologically. However, only the natural pothos stimulus showed a sense of physiological calm in the same appearance as the fabric stimulus.Conclusions
This study shows that people experience an unconscious calming reaction to touching a plant. It is to be concluded that plants are an indispensable element of the human environment. 相似文献20.
Astrid Stumpf Markus Burgmer Gudrun Schneider Gereon Heuft Martin Schmelz Ngoc Quan Phan Sonja St?nder Bettina Pfleiderer 《PloS one》2013,8(11)