Browsing by Subject "REPRODUCIBILITY"

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  • Rueegg, Corina S.; Stenehjem, Jo S.; Egger, Matthias; Ghiasvand, Reza; Cho, Eunyoung; Lund, Eiliv; Weiderpass, Elisabete; Green, Adele C.; Veierod, Marit B. (2019)
    Whether sunscreen use affects melanoma risk has been widely studied with contradictory results. To answer this question we performed a systematic review of all published studies, accounting for sources of heterogeneity and bias. We searched for original articles investigating the sunscreen-melanoma association in humans to February 28, 2018. We then used random-effects meta-analysis to combine estimates of the association, stratified by study design. Stratified meta-analysis and meta-regression were used to identify sources of heterogeneity. We included 21,069 melanoma cases from 28 studies published 1979-2018: 23 case-control (11 hospital-based, 12 population-based), 1 ecological, 3 cohort and 1 randomised controlled trial (RCT). There was marked heterogeneity across study designs and among case-control studies but adjustment for confounding by sun exposure, sunburns and phenotype systematically moved estimates toward decreased melanoma risk among sunscreen users. Ever- vs. never-use of sunscreen was inversely associated with melanoma in hospital-based case-control studies (adjusted odds ratio (OR) = 0.57, 95%confidence interval (CI) 0.37-0.87, p(heterogeneity) <0.001), the ecological study (rate ratio = 0.48, 95%CI 0.35-0.66), and the RCT (hazard ratio (HR) = 0.49, 95%CI 0.24-1.01). It was not associated in population-based case-control studies (OR = 1.17, 95%CI 0.90-1.51, p(heterogeneity) <0.001) and was positively associated in the cohort studies (HR = 1.27, 95%CI 1.07-1.51, p(heterogeneity) = 0.236). The association differed by latitude (p(interaction) = 0.042), region (p(interaction) = 0.008), adjustment for naevi/freckling (p(interaction) = 0.035), and proportion of never-sunscreen-users (p(interaction) = 0012). Evidence from observational studies on sunscreen use and melanoma risk was weak and heterogeneous, consistent with the challenges of controlling for innate confounding by indication. The only RCT showed a protective effect of sunscreen. What's new? Effectiveness of sunscreen in reducing UV-induced skin damage has been proven in experimental studies, but effectiveness in reducing melanoma in humans remains inconclusive. This is the first meta-analysis to analyze data from four study designs, stratify hospital- and population-based case-control studies, and include as many as five prospective studies. Evidence from observational studies on the sunscreen-melanoma association was heterogeneous, consistent with the challenges of controlling for innate confounding by indication. The only randomized controlled trial showed a protective effect. Public health recommendations should place greater emphasis on the proper use of sunscreen in conjunction with other means of sun protection.
  • Tedersoo, Leho; Kungas, Rainer; Oras, Ester; Köster, Kajar; Eenmaa, Helen; Leijen, Ali; Pedaste, Margus; Raju, Marju; Astapova, Anastasiya; Lukner, Heli; Kogermann, Karin; Sepp, Tuul (2021)
    Data sharing is one of the cornerstones of modern science that enables large-scale analyses and reproducibility. We evaluated data availability in research articles across nine disciplines in Nature and Science magazines and recorded corresponding authors' concerns, requests and reasons for declining data sharing. Although data sharing has improved in the last decade and particularly in recent years, data availability and willingness to share data still differ greatly among disciplines. We observed that statements of data availability upon (reasonable) request are inefficient and should not be allowed by journals. To improve data sharing at the time of manuscript acceptance, researchers should be better motivated to release their data with real benefits such as recognition, or bonus points in grant and job applications. We recommend that data management costs should be covered by funding agencies; publicly available research data ought to be included in the evaluation of applications; and surveillance of data sharing should be enforced by both academic publishers and funders. These cross-discipline survey data are available from the plutoF repository.
  • Konstari, Sanna; Sares-Jäske, Laura; Heliövaara, Markku; Rissanen, Harri; Knekt, Paul; Arokoski, Jari; Sundvall, Jouko; Karppinen, Jaro (2019)
    Objectives To study whether low dietary magnesium (Mg) intake and serum high sensitivity C-reactive protein (hs-CRP) predict the development of clinical knee osteoarthritis (OA). Methods The cohort consisted of 4,953 participants of a national health examination survey who were free of knee and hip OA at baseline. Information on the incidence of knee OA leading to hospitalization was drawn from the National Care Register for Health Care. During the follow-up of 10 years, 123 participants developed incident knee OA. Dietary magnesium intake was assessed on the basis of a food frequency questionnaire from the preceding year. We used Cox's proportional hazards model to estimate the strength of the association between the tertiles of dietary Mg intake and incident knee OA, adjusted for baseline age, gender, energy intake, BMI, history of physical workload, leisure time physical activity, injuries, knee complaints, the use of Mg supplements, and serum hs-CRP levels. Results At baseline, dietary Mg intake was inversely associated with serum hs-CRP even after adjustment for all the potential confounding factors. During the follow-up, the adjusted hazard ratios (with their 95% confidence intervals) for incident knee OA in dietary Mg intake tertiles were 1.00, 1.28 (0.78-2.10), and 1.38 (0.73-2.62); the p value for trend was 0.31. Serum hs-CRP level at baseline did not predict incident knee OA. Conclusions The results do not support the hypothesis that low dietary Mg intake contributes to the development of clinical knee OA, although Mg intake is inversely associated with serum hs-CRP level.
  • Martinez-Majander, Nicolas; Gordin, Daniel; Joutsi-Korhonen, Lotta; Salopuro, Titta; Adeshara, Krishna; Sibolt, Gerli; Curtze, Sami; Pirinen, Jani; Liebkind, Ron; Soinne, Lauri; Sairanen, Tiina; Sinisalo, Juha; Lehto, Mika; Groop, Per-Henrik; Tatlisumak, Turgut; Putaala, Jukka (2021)
    Background The aim of this study was to assess the association between endothelial function and early-onset cryptogenic ischemic stroke (CIS), with subgroup analyses stratified by sex and age groups. Methods and Results We prospectively enrolled 136 consecutive patients aged 18 to 49 years (median age, 41 years; 44% women) with a recent CIS and 136 age- and sex-matched (+/- 5 years) stroke-free controls. Endothelial function was measured with an EndoPAT 2000 device and analyzed as tertiles of natural logarithm of reactive hyperemia index with lower values reflecting dysfunction. We used conditional logistic regression adjusting for age, education, hypertension, diabetes mellitus, dyslipidemia, current smoking, heavy drinking, obesity, and diet score to assess the independent association between endothelial function and CIS. Patients in the lowest tertile of natural logarithm of reactive hyperemia index were more often men and they more frequently had a history of dyslipidemia; they were also more often obese, had a lower diet score, and lower high-density lipoprotein cholesterol. In the entire cohort, we found no association in patients with endothelial function and CIS compared with stroke-free controls. In sex- and age-specific analyses, endothelial dysfunction was associated with CIS in men (adjusted odds ratio [OR], 3.50 for lowest versus highest natural logarithm of reactive hyperemia index tertile; 95% CI, 1.22-10.07) and in patients >= 41 years (OR, 5.78; 95% CI, 1.52-21.95). These associations remained significant when dyslipidemia was replaced with the ratio of total to high-density lipoprotein cholesterol. Conclusions Endothelial dysfunction appears to be an independent player in early-onset CIS in men and patients approaching middle age.
  • Ahlgren, Johanna; Voikar, Vootele (2019)
    Low replicability of animal experiments is perceived as a major hurdle in the field of biomedicine. Attempts to enhance the replicability and to reduce the variability in basic research has led to the recommendation to use isogenic mice. The C57BL/6 strain has evolved as a gold standard strain for this purpose. However, C57BL/6 mice are maintained as substrains by multiple vendors. Evidence exists that the subtle differences between these mouse lines have not been systematically investigated and are often ignored. In the present study, we characterized the female mice of two closely related substrains (C57BL/6J and C57BL/6N) from three vendors in Europe (Charles River Laboratories, Envigo, Janvier Labs) in a battery of behavioral tests. Our data show and confirm substantial behavioral differences between the C57BL/6J and C57BL/6N mice. Importantly, the substrain differences were largely affected by the origin of the animals, as a significant effect of vendor or interaction between the substrain and vendor occurred in all tests. This work highlights the importance of adhering to precise international nomenclature in all publications reporting animal experiments. Moreover, the generalization of research findings from a single mouse substrain can be seriously limited due to genetic drift and environmental variables occurring at different vendors. However, heterogenization of samples, by including animals of different substrains, can enhance generalizability. These issues need to be seriously addressed to improve reproducibility, replicability, and the translational potential of the mouse models.
  • Lofvenborg, J. E.; Andersson, T.; Carlsson, P-O; Dorkhan, M.; Groop, L.; Martinell, M.; Tuomi, T.; Wolk, A.; Carlsson, S. (2014)
  • Helin, Henrik O.; Tuominen, Vilppu J.; Ylinen, Onni; Helin, Heikki; Isola, Jorma (2016)
    Evaluation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) is subject to interobserver variation and lack of reproducibility. Digital image analysis (DIA) has been shown to improve the consistency and accuracy of the evaluation and its use is encouraged in current testing guidelines. We studied whether digital image analysis using a free software application (ImmunoMembrane) can assist in interpreting HER2 IHC in equivocal 2+ cases. We also compared digital photomicrographs with whole-slide images (WSI) as material for ImmunoMembrane DIA. We stained 750 surgical resection specimens of invasive breast cancers immunohistochemically for HER2 and analysed staining with ImmunoMembrane. The ImmunoMembrane DIA scores were compared with the originally responsible pathologists' visual scores, a researcher's visual scores and in situ hybridisation (ISH) results. The originally responsible pathologists reported 9.1 % positive 3+ IHC scores, for the researcher this was 8.4 % and for ImmunoMembrane 9.5 %. Equivocal 2+ scores were 34 % for the pathologists, 43.7 % for the researcher and 10.1 % for ImmunoMembrane. Negative 0/1+ scores were 57.6 % for the pathologists, 46.8 % for the researcher and 80.8 % for ImmunoMembrane. There were six false positive cases, which were classified as 3+ by ImmunoMembrane and negative by ISH. Six cases were false negative defined as 0/1+ by IHC and positive by ISH. ImmunoMembrane DIA using digital photomicrographs and WSI showed almost perfect agreement. In conclusion, digital image analysis by ImmunoMembrane can help to resolve a majority of equivocal 2+ cases in HER2 IHC, which reduces the need for ISH testing.
  • Glaus, Peter; Honkela, Antti; Rattray, Magnus (2012)
    Motivation: High-throughput sequencing enables expression analysis at the level of individual transcripts. The analysis of transcriptome expression levels and differential expression (DE) estimation requires a probabilistic approach to properly account for ambiguity caused by shared exons and finite read sampling as well as the intrinsic biological variance of transcript expression. Results: We present Bayesian inference of transcripts from sequencing data (BitSeq), a Bayesian approach for estimation of transcript expression level from RNA-seq experiments. Inferred relative expression is represented by Markov chain Monte Carlo samples from the posterior probability distribution of a generative model of the read data. We propose a novel method for DE analysis across replicates which propagates uncertainty from the sample-level model while modelling biological variance using an expression-level-dependent prior. We demonstrate the advantages of our method using simulated data as well as an RNA-seq dataset with technical and biological replication for both studied conditions. Availability: The implementation of the transcriptome expression estimation and differential expression analysis, BitSeq, has been written in C++ and Python. The software is available online from, version 0.4 was used for generating results presented in this article.
  • Allkja, Jontana; van Charante, Frits; Aizawa, Juliana; Reigada, Ines; Guarch-Perez, Clara; Vazquez-Rodriguez, Jesus Augusto; Cos, Paul; Coenye, Tom; Fallarero, Adyary; Zaat, Sebastian A. J.; Felici, Antonio; Ferrari, Livia; Azevedo, Nuno F.; Parker, Albert E.; Goeres, Darla M. (2021)
    Microtiter plate methods are commonly used for biofilm assessment. However, results obtained with these methods have often been difficult to reproduce. Hence, it is important to obtain a better understanding of the repeatability and reproducibility of these methods. An interlaboratory study was performed in five different laboratories to evaluate the reproducibility and responsiveness of three methods to quantify Staphylococcus aureus biofilm formation in 96-well microtiter plates: crystal violet, resazurin, and plate counts. An inter-lab protocol was developed for the study. The protocol was separated into three steps: biofilm growth, biofilm challenge, biofilm assessment. For control experiments participants performed the growth and assessment steps only. For treatment experiments, all three steps were performed and the efficacy of sodium hypochlorite (NaOCl) in killing S. aureus biofilms was evaluated. In control experiments, on the log(10)-scale, the reproducibility SD (S-R) was 0.44 for crystal violet, 0.53 for resazurin, and 0.92 for the plate counts. In the treatment experiments, plate counts had the best responsiveness to different levels of efficacy and also the best reproducibility with respect to responsiveness (Slope/S-R=1.02), making it the more reliable method to use in an antimicrobial efficacy test. This study showed that the microtiter plate is a versatile and easy-to-use biofilm reactor, which exhibits good repeatability and reproducibility for different types of assessment methods, as long as a suitable experimental design and statistical analysis is applied.
  • Korkalo, Liisa; Vepsäläinen, Henna; Ray, Carola; Skaffari, Essi; Lehto, Reetta; Hauta-alus, Helena Henrietta; Nissinen, Kaija; Meinilä, Jelena; Roos, Eva; Erkkola, Maijaliisa (2019)
    The accurate assessment of food consumption is crucial in nutritional studies. Since modern nutrition science has become more interested in diet as a whole, studies validating food frequency questionnaires (FFQs) and exploratory dietary patterns are needed. We aimed at examining the relative validity of a 47-item FFQ against three-day food records among three- to six-year-old Finnish children, as well as investigating the consistency of the dietary patterns derived using the principal component analysis (PCA), with food record and FFQ data as inputs. We conducted the PCA without forcing the food record data to match the FFQ items. Altogether, 75% or more of the participants were classified into the same or adjacent quarter of vegetables and fruits as well as sugary food consumption. Furthermore, the intake of folate and vitamin C increased linearly in the quarters of vegetable and fruit consumption, as did the intake of sucrose in quarters of sugary food consumption. Three fairly similar dietary patterns were identified from food records and FFQ data. Concerning the patterns, more than 70% of the participants were classified into the same or adjacent quarter. However, the Spearman correlation coefficients between the respective pattern scores were low (0.25-0.33). The FFQ showed acceptable validity when ranking food group consumption compared to food records. Additionally, the FFQ-derived dietary patterns were consistent with those derived using food record data.
  • Simpson, Samantha; Kaislasuo, Janina; Guller, Seth; Pal, Lubna (2020)
    Background: The role of cytokines in various disease states is a burgeoning field of academic study and clinical application, however there are no consensus documents on how certain cytokines should be stored prior to quantification. This information is especially of interest to researchers assembling a biobank or clinicians who have to transport specimens to a different location in order to be tested. Objective: To review the literature and synthesize prior findings on cytokine storage and freeze/thaw stability. Design: We searched PubMed for articles related to cytokine storage stability. All articles were analyzed for cytokines studied, source of reported cytokine concentration (i.e., human whole blood or serum, concentrations from other species or bodily sources were excluded), and reported statistical results. Results: We identified and synthesized results of 23 peer-reviewed articles which published data on the storage and freeze/thaw stability of 33 different cytokines and chemokines. Conclusion: There is a wide variety of reported cytokine storage and freeze/thaw stability. Interleukin-6 and tumor necrosis factor alpha are the most widely studied cytokines in regard to temperature stability. In a few cytokines, a clear consensus can be reached as to storage safety at particular temperatures, but in most, more research needs to be done and we advise the clinician or researcher to use caution in interpreting cytokine concentration results after a long period of storage or several freeze/thaw cycles.
  • Ahonen, L.; Huotilainen, M.; Brattico, E. (2016)
    In the vast majority of electrophysiological studies on cognition, participants are only measured once during a single experimental session. The dearth of studies on test-retest reliability in magnetoencephalography (MEG) within and across experimental sessions is a preventing factor for longitudinal designs, imaging genetics studies, and clinical applications. From the recorded signals, it is not straightforward to draw robust and steady indices of brain activity that could directly be used in exploring behavioral effects or genetic associations. To study the variations in markers associated with cognitive functions, we extracted three event-related field (ERF) features from time-locked global field power (GFP) epochs using MEG while participants were performing a numerical N-back task in four consecutive measurements conducted during two different days separated by two weeks. We demonstrate that the latency of the MI70, a neural correlate associated with cognitive functions such as working memory, was a stable parameter and did not show significant variations over time. In addition, the M170 peak amplitude and the mean amplitude of late positive component (LPP) also expressed moderate-to-strong reliability across multiple measures over time over many sensor spaces and between participants. The M170 amplitude varied more significantly between the measurements in some conditions but showed consistency over the participants over time. In addition we demonstrated significant correlation with the M170 and LPP parameters and cognitive load. The results are in line with the literature showing less within-subject fluctuation for the latency parameters and more consistency in between-subject comparisons for amplitude based features. The within-subject consistency was apparent also with longer delays between the measurements. We suggest that with a few limitations the ERF features show sufficient reliability and stability for longitudinal research designs and clinical applications for cognitive functions in single as well as cross-subject designs. (C) 2016 Elsevier Inc. All rights reserved.