| 1. |
- Brunius, Carl, 1974, et al.
(författare)
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Prediction and modeling of pre-analytical sampling errors as a strategy to improve plasma NMR metabolomics data
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1460-2059 .- 1367-4811. ; 33:22, s. 3567-3574
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g. collection and processing of biological samples is highly complex, with many variables that could alter sample integrity and even more complex when considering multiple study centers or using legacy samples with limited documentation on sample management. Novel means to understand and take into account such variability would enable high-quality research on archived samples. This study investigated whether pre-analytical sample variability could be predicted and reduced by modeling alterations in the plasma metabolome, measured by NMR, as a function of pre-centrifugation conditions (1-36 h pre-centrifugation delay time at 4 A degrees C and 22 A degrees C) in 16 individuals. Pre-centrifugation temperature and delay times were predicted using random forest modeling and performance was validated on independent samples. Alterations in the metabolome were modeled at each temperature using a cluster-based approach, revealing reproducible effects of delay time on energy metabolism intermediates at both temperatures, but more pronounced at 22 A degrees C. Moreover, pre-centrifugation delay at 4 A degrees C resulted in large, specific variability at 3 h, predominantly of lipids. Pre-analytical sample handling error correction resulted in significant improvement of data quality, particularly at 22 A degrees C. This approach offers the possibility to predict pre-centrifugation delay temperature and time in biobanked samples before use in costly downstream applications. Moreover, the results suggest potential to decrease the impact of undesired, delay-induced variability. However, these findings need to be validated in multiple, large sample sets and with analytical techniques covering a wider range of the metabolome, such as LC-MS.
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| 2. |
- Tomba, Gianpaolo Scalia, et al.
(författare)
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Some model based considerations on observing generation times for communicable diseases
- 2010
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Ingår i: Mathematical Biosciences. - : Elsevier BV. - 0025-5564 .- 1879-3134. ; 223:1, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- The generation time of an infectious disease is usually defined as the time from the moment one person becomes infected until that person infects another person. The concept is similar to ""generation gap"" in demography, with new infections replacing births in a population. Originally applied to diseases such as measles where at least the first generations are clearly discernible, the concept has recently been extended to other diseases, such as influenza, where time order of infections is usually much less apparent. By formulating the relevant statistical questions within a simple yet basic mathematical model for infection spread, it is possible to derive theoretical properties of observations in various situations e.g. in ""isolation"", in households, or during large outbreaks. In each case, it is shown that the sampling distribution of observations depends on a number of factors, usually not considered in the literature and that must be taken into account in order to achieve unbiased inference about the generation time distribution. Some implications of these findings for statistical inference methods in epidemic spread models are discussed.
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| 3. |
- Sjolander, Arvid, et al.
(författare)
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Sensitivity Analysis for Principal Stratum Direct Effects, with an Application to a Study of Physical Activity and Coronary Heart Disease
- 2009
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Ingår i: Biometrics. - : Wiley. - 0006-341X .- 1541-0420. ; 65:2, s. 514-520
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Tidskriftsartikel (refereegranskat)abstract
- In many studies, the aim is to learn about the direct exposure effect, that is, the effect not mediated through an intermediate variable. For example, in circulation disease studies it may be of interest to assess whether a suitable level of physical activity can prevent disease, even if it fails to prevent obesity. It is well known that stratification on the intermediate may introduce a so-called posttreatment selection bias. To handle this problem, we use the framework of principal stratification (Frangakis and Rubin, 2002, Biometrics 58, 21-29) to define a causally relevant estimand-the principal stratum direct effect (PSDE). The PSDE is not identified in our setting. We propose a method of sensitivity analysis that yields a range of plausible values for the causal estimand. We compare our work to similar methods proposed in the literature for handling the related problem of ""truncation by death."".
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| 4. |
- Christidis, Maria, 1982-, et al.
(författare)
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Mathematics as an aspect of vocational knowing in animal caregiving, from a student perspective
- 2024
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Ingår i: Learning, Culture and Social Interaction. - : Elsevier. - 2210-6561 .- 2210-657X. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to explore whether and how students experience mathematics as an aspect of vocational knowing in the Swedish upper secondary Natural Resource Programme, in the orientation of animal care, and in the vocation. Data for the study comprised teacher's documented planning, student interviews, followed by a validation of the interviews. Data were initially analysed thematically. Thereafter, the themes were analysed with theoretical concepts from the theory of practice architectures (sayings, doings, and relatings), and interpreted in terms of characteristic arrangements (cultural-discursive, material-economic, and social-political). Themes identified in the student interviews were: 1) Vocational knowing in animal caregiving 2) Mathematics as vocational knowing 3) Mathematics as part of vocational language, and 4) Mathematics as a foundation subject. Sayings were also related to doings, because of the accessibility and character of data. It was evident that students recognized mathematics as an aspect of vocational knowing, but there was also a tension between this mathematics and for the school/as a foundation subject. Relatings represented the recurrent contexts of school, animal facilities, workplace learning but also laws and regulations for contemporary animal care. Further analysis was made to historical traces of previous education within the area and to political decisions.
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| 5. |
- Dahlström, Lisen Arnheim, et al.
(författare)
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Prospective study of human papillomavirus and risk of cervical adenocarcinoma.
- 2010
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 127:8, s. 1923-30
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population-based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow-up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6-46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8-66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5-192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8-206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.
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| 6. |
- Leu, Monica, et al.
(författare)
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NordicDB : a Nordic pool and portal for genome-wide control data
- 2010
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 18:12, s. 1322-1326
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Tidskriftsartikel (refereegranskat)abstract
- A cost-efficient way to increase power in a genetic association study is to pool controls from different sources. The genotyping effort can then be directed to large case series. The Nordic Control database, NordicDB, has been set up as a unique resource in the Nordic area and the data are available for authorized users through the web portal (http://www.nordicdb.org). The current version of NordicDB pools together high-density genome-wide SNP information from similar to 5000 controls originating from Finnish, Swedish and Danish studies and shows country-specific allele frequencies for SNP markers. The genetic homogeneity of the samples was investigated using multidimensional scaling (MDS) analysis and pairwise allele frequency differences between the studies. The plot of the first two MDS components showed excellent resemblance to the geographical placement of the samples, with a clear NW-SE gradient. We advise researchers to assess the impact of population structure when incorporating NordicDB controls in association studies. This harmonized Nordic database presents a unique genome-wide resource for future genetic association studies in the Nordic countries. European Journal of Human Genetics (2010) 18, 1322-1326; doi: 10.1038/ejhg.2010.112; published online 28 July 2010
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| 7. |
- Törmä, Hans, et al.
(författare)
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Skin barrier disruption by sodium lauryl sulfate-exposure alters the expressions of involucrin, transglutaminase 1, profilaggrin, and kallikreins during the repair phase in human skin in vivo
- 2008
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Ingår i: Journal of Investigative Dermatology. - London : Nature publishing group. - 0022-202X .- 1523-1747. ; 128:5, s. 1212-1219
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Tidskriftsartikel (refereegranskat)abstract
- Detergents are skin irritants affecting keratinocytes. In this study, healthy volunteers were exposed to water (vehicle) and 1% sodium lauryl sulfate (SLS) under occlusive patch tests for 24 hours. The messenger RNA (mRNA) expression of keratinocyte differentiation markers and of enzymes involved in corneodesmosome degradation was examined in skin biopsies (n=8) during the repair phase (6 hours to 7 days postexposure) using real-time reverse-transcription PCR. It was found that the expression of involucrin was increased at 6 hours, but then rapidly normalized. The expression of transglutaminase 1 exhibited a twofold increase after 24 hours in the SLS-exposed skin. Profilaggrin was decreased after 6 hours. Later (4–7 days), the expression in SLS-exposed areas was >50% above than in control areas. An increased and altered immunofluorescence pattern of involucrin, transglutaminase 1, and filaggrin was also found (n=4). At 6 hours post-SLS exposure, the mRNA expression of kallikrein-7 (KLK-7) and kallikrein-5 (KLK-5) was decreased by 50 and 75%, respectively, as compared with control and water-exposed areas. Thereafter, the expression pattern of KLK-7 and KLK-5 was normalized. Changes in protein expression of KLK-5 were also found. In conclusion, SLS-induced skin barrier defects induce altered mRNA expression of keratinocyte differentiation markers and enzymes degrading corneodesmosomes.
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| 8. |
- Rullgard, H., et al.
(författare)
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Simulation of transmission electron microscope images of biological specimens
- 2011
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 243:3, s. 234-256
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Tidskriftsartikel (refereegranskat)abstract
- We present a new approach to simulate electron cryo-microscope images of biological specimens. The framework for simulation consists of two parts; the first is a phantom generator that generates a model of a specimen suitable for simulation, the second is a transmission electron microscope simulator. The phantom generator calculates the scattering potential of an atomic structure in aqueous buffer and allows the user to define the distribution of molecules in the simulated image. The simulator includes a well defined electron-specimen interaction model based on the scalar Schrodinger equation, the contrast transfer function for optics, and a noise model that includes shot noise as well as detector noise including detector blurring. To enable optimal performance, the simulation framework also includes a calibration protocol for setting simulation parameters. To test the accuracy of the new framework for simulation, we compare simulated images to experimental images recorded of the Tobacco Mosaic Virus (TMV) in vitreous ice. The simulated and experimental images show good agreement with respect to contrast variations depending on dose and defocus. Furthermore, random fluctuations present in experimental and simulated images exhibit similar statistical properties. The simulator has been designed to provide a platform for development of new instrumentation and image processing procedures in single particle electron microscopy, two-dimensional crystallography and electron tomography with well documented protocols and an open source code into which new improvements and extensions are easily incorporated.
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| 9. |
- Lu, Xin, et al.
(författare)
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Respondent-driven sampling on directed networks
- 2013
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Ingår i: Electronic Journal of Statistics. - 1935-7524. ; 7, s. 292-322
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Tidskriftsartikel (refereegranskat)abstract
- Respondent-driven sampling (RDS) is a widely used method for generating chain-referral samples from hidden populations. It is an extension of the snowball sampling method and can, given that some assumptions are met, generate unbiased population estimates. One key assumption, not likely to be met, is that the acquaintance network in which the recruitment process takes place is undirected, meaning that all recruiters should have the potential to be recruited by the person they recruit. Using a mean-field approach, we develop an estimator which is based on prior information about the average indegrees of estimated variables. When the indegree is known, such as for RDS studies over internet social networks, the estimator can greatly reduce estimate error and bias as compared with current methods; when the indegree is not known, which is most common for interview-based RDS studies, the estimator can through sensitivity analysis be used as a tool to account for uncertainties of network directedness and error in self-reported degree data. The performance of the new estimator, together with previous RDS estimators, is investigated thoroughly by simulations on networks with varying structures. We have applied the new estimator on an empirical RDS study for injecting drug users in New York City.
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| 10. |
- Ohst, Jan, et al.
(författare)
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The network positions of methicillin resistant Staphylococcus aureus affected units in a regional healthcare system
- 2014
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Ingår i: EPJ data science. - : Springer Science and Business Media LLC. - 2193-1127. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- We studied a dataset of care episodes in a regional Swedish hospital system. We followed how 2,314,477 patients moved between 8,507 units (hospital wards and outpatient clinics) over seven years. The data also included information on the date when patients tested positive with methicillin resistant Staphylococcus aureus. To simplify the complex flow of patients, we represented it as a network of units, where two units were connected if a patient moved from one unit to another, without visiting a third unit in between. From this network, we characterized the typical network position of units with a high prevalence of methicillin resistant Staphylococcus aureus, and how the patient's location in the network changed upon testing positive. On average, units with medium values of the analyzed centrality measures had the highest average prevalence. We saw a weak effect of the hospital system's response to the patient testing positive - after a positive test, the patient moved to units with a lower centrality measured as degree (i.e. number of links to other units) and in addition, the average duration of the care episodes became longer. The network of units was too random to be a strong predictor of the presence of methicillin resistant Staphylococcus aureus - would it be more regular, one could probably both identify and control outbreaks better. The migration of the positive patients with within the healthcare system, however, helps decreasing the outbreak sizes.
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