Misleading Data Research Articles

The Predicted Molecular Weight of Nrf2: It Is What It Is Not

The Predicted Molecular Weight of Nrf2: It Is What It Is Not

Faulty Conclusions Built on Shoddy Foundations

Faulty Conclusions Built on Shoddy Foundations

A comprehensive 16 loci-based DNA fingerprinting dataset of a broad tumor cell line panel for cancer research

Motivations. Tumor cell lines are widely used as in vitro models and as screening tools in cancer research. A significant portion of cell lines have been reported to be misidentified, potentially generating misleading data interpretation. Correct assessment of cell line genetic identity is therefore critical to cancer biology studies as well as to drug discovery. Several methods may be applied to authenticate cell lines, but DNA fingerprinting based on the detection of Short Tandem Repeats (STR) has emerged as the standard approach. STR profiles for several commercial cell lines can be retrieved from sparse literature reports or from vendor databases, however these are mainly based on the analysis of 8 loci, except for the NCI60 panel, on which 16 loci were profiled. Inconsistencies can be found in allele designation among the different authors, mainly when more than two alleles per locus are present, as is frequently found in tumor cell lines. A resource to facilitate literature interrogation is represented by the Cell Line Integrated Molecular Authentication database (CLIMA), but to date there are no reported comprehensive databases containing 16 loci profile sets generated in parallel. Here we disclose the in-house generation of a homogeneous 16 loci dataset, reporting the STR profiles for a panel of about 300 tumor cell lines, representative of diverse solid and circulating tumor types. Our intent was to facilitate the management of the internal cell bank, by assessing the identity and stability over time of the tumor cell lines used for research, with the highest accuracy in discrimination and with an optimized score for profile similarity checking. The STR database can be linked to Nerviano Medical Sciences (NMS) internal database, which contains information on cell line origin, morphology, growth conditions, as well as known somatic mutations (from the Wellcome Trust Sanger Institute Cosmic database), thus making it a comprehensive integrated platform for cell line utilization in drug discovery. Our plan is to make the STR database available to the scientific community. Methods. DNA fingerprinting is based on the simultaneous amplification of highly polymorphic STR sites, which are short DNA sequences with a varying number of repeats in each cell line. Genetic abnormalities in tumor cell lines can result in more than two alleles at each locus, which complicates the analysis. Most STR profiles reported so far are based on the analysis of a limited number of STR loci, usually 8. The probability for two individuals to share the same STR profile is estimated to range from ~10-8 for 8 loci to ~10-17 for 16 loci. A 16 loci profile can be beneficial in cancer research, due to the intrinsic genetic instability of tumor cells that may result in allele acquisition or loss. In the current study we performed a 16-loci STR fingerprinting analysis on a panel of about 300 commercially available cancer cell lines. DNA was prepared directly from frozen cells, using NucleoSpin Tissue (Macherey-Nagel), and then analysed using AmpFlSTR Identifiler Plus PCR Amplification kit (Applied Biosystems), that amplifies simultaneously 15 tetranucleotide repeat loci and the amelogenin gender marker. For a more accurate comparison of STR profiles in different cell lines, we have introduced a modification to the standard calculation of similarity scores to account for partial allele identity at each locus, allowing a more precise definition of the level of similarity, which is particularly relevant when multiple alleles are present. This is obtained by applying the following formula that calculates the number of identical alleles at each locus, divided by the total number of alleles: given a cell line A and a cell line B, the score is defined as the identified sum of similarities at each i-th locus s(i) normalized by the number of not empty loci, where s(i) = 2 x [alleles(A) = alleles(B)] / [#alleles(A) + #alleles(B)]. Based on a preliminary sensitivity analysis, the similarity score threshold to classify two cell lines as identical was set at 80%. Results. A DNA fingerprinting analysis based on 16 loci was performed on a panel of about 300 widely used tumor cell lines, purchased at NMS over several years from diverse providers. Using an established cut off of 80%, we found that all cell lines were correctly classified, suggesting that the cell line panel is genetically stable over time. As expected, an overall pairwise analysis of all the different cell line profiles revealed a generally low similarity degree (less than 50%), with no evidence for any similarity bias due to tumor type. The main outcome of this study is the availability of a large 16 loci STR dataset of tumor cell lines, which was integrated as a fundamental part of the NMS Cell Bank database. The STR dataset can be easily interrogated and distributed for use as a reliable reference for cancer research.

The dominance of Big Pharma: unhealthy relationships?

The multinational pharmaceutical industry is seldom out of the news for a variety of reasons. ‘‘Breakthroughs’’ in drug treatment are acclaimed in the press, yet the industry’s reputation is frequently tarnished by claims of profiteering, data ‘‘massaging’’ and inappropriate marketing techniques that include inducements offered to healthcare professionals, promoting misleading data and questionable direct-toconsumer advertising. The industry has also been accused of ignoring low-incidence diseases in developed Western countries and common, life-threatening disease in others on grounds of poor profitability. At heart, there are pressing concerns about power relationships, and considerations of trust at several levels that have never been fully resolved. Most of the papers included in this themed section emerged from those presented and discussed at a seminar held during a conference of the European Society for Philosophy, Medicine and Health Care at the University of Tubingen during August 2009. These papers are supplemented by a contribution that considers the potential for bias in the uncertain process of appraisals by the UK National Institute for Health and Clinical Excellence, a process whose outcomes are crucial for patients, prescribers and manufacturers, together with a polemical debate between two general medical practitioners, one from Germany and one from the UK concerning their personal views on attempts by some industry employees to subvert or evade regulatory practices to maintain progress. The paper by Badcott, Big Pharma: a Former Insider’s View summarises the main components that support a generally instrumental justification for the commercial and highly competitive nature of the industry. It is argued that the established operational model optimises development of increasingly more effective and better tolerated new medicines, funded by investment and maintained through the profits of direct market competition. Nevertheless, major ethical problems are acknowledged within the industry and whilst their seeming ubiquity and refractory nature is in itself problematic—human ingenuity at circumventing codes and regulation that are perceived as more of a challenge than a bar is undeniable—there are encouraging signs that some major multinational Big Pharma companies are beginning to adopt more rigorous and accountable ethical codes, some of which reflect acknowledgment of the value of adopting a triple bottom line policy and shouldering wider social and other responsibilities. General medical practitioners and hospital doctors are the principle targets for pharmaceutical promotion. In Of Mugs, Meals and More—the Intricate Relations Between Physicians and the Medical industry, Sahm explores some of the main aspects of this relationship which has often been plagued by ethical problems for both parties. Physicians are the principle gatekeepers for the accessibility of potent medicines by patients and Sahm recognises that ‘‘co-operation between profit-driven manufacturers of medical products and physicians caring for patients is D. Badcott (&) Centre for Applied Ethics, Cardiff University, Humanities Building, Colum Drive, Cardiff CF10 3EU, UK e-mail: badcottd@cf.ac.uk

Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence

Experimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species.

Improving seizure recognition by visual reinforcement

ObjectiveExact seizure description is an important diagnostic tool of epilepsy; however, epileptologists frequently get misleading data from lay eyewitnesses. The aim of this study is to find new methods for efficient training of seizure observation. MethodsTwelve video-recorded seizures were observed by four groups of subjects with different expertise level in epilepsy: (1) naïve observers, (2) pediatric residents, (3) epilepsynurses, and (4) experts in video-EEG monitoring. In half of the experiments, relevant parts of seizures were highlighted to direct the subjects’ gaze during observations. Eye motion data of the observers were recorded by a Tobii T120 Eye Tracking system. After watching a seizure, subjects were asked to fill out a questionnaire regarding semiology data. To reinforce associations between verbal and visual information, subjects watched again the same clip. Observation skill improvement was accessed by comparing questionnaire scores and eye fixation data. ResultsQuestionnaire mean scores increased and deviations decreased through the study demonstrating overall improvement for each group. Fixation time values were shorter in more experienced observers, however, this difference diminished by time reflecting the effect of the learning process. The chosen method for visual highlighting did not facilitate learning. ConclusionsOur pilot study – using eye-tracking assessment in clinical epileptology for the first time – shows that seizure observational skills can be significantly facilitated by a combined use of video examples and questionnaires. With the increasing popularity of eye-tracking methods in applied sciences, our results may lead to novel approaches in epilepsy education of both lay subjects and professionals.

The efficacy of field techniques for obtaining and storing blood samples from fishes

Prompted by the dramatic increase in the use of blood analyses in fisheries research and monitoring, this study investigated the efficacy of common field techniques for sampling and storing blood from fishes. Three questions were addressed: (1) Do blood samples taken via rapid caudal puncture (the 'grab-and-stab' technique) yield similar results for live v. sacrificed groups of fishes? (2) Do rapidly obtained caudal blood samples accurately represent blood properties of fishes prior to capture? (3) Does storage of whole blood in an ice slurry for a working day (8·5 h) modify the properties of the plasma? It was shown that haematocrit, plasma ions, metabolites, stress hormones and sex hormones of caudal blood samples were statistically similar when taken from live v. recently sacrificed groups of adult coho salmon Oncorhynchus kisutch. Moreover, this study confirmed by using paired blood samples from cannulated O. kisutch that blood acquired through the caudal puncture technique (mean ±s.e. 142 ± 26 s after capture) was representative of fish prior to capture. Long-term (8·5 h) cold storage of sockeye salmon Oncorhynchus nerka whole blood caused significant decreases in plasma potassium and chloride, and a significant increase in plasma glucose. Previous research has suggested that these changes largely result from net movements of ions and molecules between the plasma and erythrocytes, movements that can occur within minutes of storage. Thus, blood samples from fishes should be centrifuged as quickly as practicable in the field for separation of plasma and erythrocytes to prevent potentially misleading data.

Harmonic component detection: Optimized Spectral Kurtosis for operational modal analysis

This work is a contribution in the field of Operational Modal Analysis to identify the modal parameters of mechanical structures using only measured responses. The study deals with structural responses coupled with harmonic components amplitude and frequency modulated in a short range, a common combination for mechanical systems with engines and other rotating machines in operation. These harmonic components generate misleading data interpreted erroneously by the classical methods used in OMA. The present work attempts to differentiate maxima in spectra stemming from harmonic components and structural modes. The detection method proposed is based on the so-called Optimized Spectral Kurtosis and compared with others definitions of Spectral Kurtosis described in the literature. After a parametric study of the method, a critical study is performed on numerical simulations and then on an experimental structure in operation in order to assess the method's performance.

Vernacular resistance to data collection and analysis: A political theory of obfuscation

Computer-enabled data collection, aggregation, and mining dramatically change the nature of contemporary surveillance. Refusal is not a practical option, as data collection is an inherent condition of many essential societal transactions. We present one vernacular response to this regime of everyday surveillance, a tactic we call obfuscation. With a variety of possible motivations, actors engage in obfuscation by producing misleading, false, or ambiguous data with the intention of confusing an adversary or simply adding to the time or cost of separating bad data from good. Our paper develops a political theory of obfuscation, linking contemporary and historical cases to develop a descriptive account of obfuscation that is able to capture key commonalities in systems from radar chaff to BitTorrent.

Singlet Oxygen Sensor Green®: Photochemical Behavior in Solution and in a Mammalian Cell

The development of efficient and selective luminescent probes for reactive oxygen species, particularly for singlet molecular oxygen, is currently of great importance. In this study, the photochemical behavior of Singlet Oxygen Sensor Green(®) (SOSG), a commercially available fluorescent probe for singlet oxygen, was examined. Despite published claims to the contrary, the data presented herein indicate that SOSG can, in fact, be incorporated into a living mammalian cell. However, for a number of reasons, caution must be exercised when using SOSG. First, it is shown that the immediate product of the reaction between SOSG and singlet oxygen is, itself, an efficient singlet oxygen photosensitizer. Second, SOSG appears to efficiently bind to proteins which, in turn, can influence uptake by a cell as well as behavior in the cell. As such, incorrect use of SOSG can yield misleading data on yields of photosensitized singlet oxygen production, and can also lead to photooxygenation-dependent adverse effects in the system being investigated.

Determining Site Size and Structure: A Fort Ancient Example

A basic problem in archaeological research is determining site size and structure. In this paper we develop an approach that sequentially employs several survey techniques, including aerial photography, magnetic gradiometry, magnetic susceptibility, and shovel testing in the context of the Wildcat site (33My499), a Fort Ancient habitation site located near Dayton, Ohio. Defining site size and structure was a challenge at Wildcat since it is located in an agricultural field that has not been plowed for many years. Magnetic susceptibility and close-interval shovel testing worked well to define the basic site structure, and magnetic gradiometry and targeted magnetic anomaly excavations efficiently revealed a series of features. Alone, each of the methods produced somewhat misleading data regarding site size and structure, but together they revealed a much smaller site than originally anticipated.

Practice guidelines for performance of the routine mid‐trimester fetal ultrasound scan

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, teaching and research for diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practices at the time at which they were issued. Although ISUOG has made every effort to ensure that guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. They are not intended to establish a legal standard of care because interpretation of the evidence that underpins the guidelines may be influenced by individual circumstances and available resources. Approved guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

Absorbance and fluorometric sensing with capillary wells microplates

Detection and readout from small volume assays in microplates are a challenge. The capillary wells microplate approach [Ng et al., Appl. Phys. Lett. 93, 174105 (2008)] offers strong advantages in small liquid volume management. An adapted design is described and shown here to be able to detect, in a nonimaging manner, fluorescence and absorbance assays minus the error often associated with meniscus forming at the air-liquid interface. The presence of bubbles in liquid samples residing in microplate wells can cause inaccuracies. Pipetting errors, if not adequately managed, can result in misleading data and wrong interpretations of assay results; particularly in the context of high throughput screening. We show that the adapted design is also able to detect for bubbles and pipetting errors during actual assay runs to ensure accuracy in screening.

Capillary Wells Microplate with Side Optical Access

The presence of bubbles in liquid samples residing in microplate wells causes inaccuracies in fluorescence measurements. In addition, pipetting errors, if not adequately managed, can result in misleading data and wrong interpretations of assay results, particularly in the context of high-throughput screening. In this work, the authors describe an adapted design to the capillary wells microplate approach that permits side viewing. They demonstrate a prototype that detects bubbles and pipetting errors during actual assay runs to ensure accuracy in screening.

Retraction Note: A novel function of poly(ADP-ribose) polymerase-1 in modulation of autophagy and necrosis under oxidative stress

The authors would like to retract the above article. Recently, the authors were alerted by the journal's editors to some discrepancies in their data. After a careful review, sufficient errors and mistakes were found that, although the authors still believe the conclusions of the paper to be valid, all the authors agreed to retract this article so as not to leave potentially misleading data in the literature.

Online advertising effectiveness: a cross‐cultural comparison

PurposeThe internet has gained enormous importance as an advertising medium. At the same time, the question of marketing accountability has become one of the top areas of research for researchers and practitioners who aim at optimal marketing budget allocations. This paper aims to show that national culture has an impact on how consumer behavior is influenced by online advertising.Design/methodology/approachThe paper compares the effectiveness of internet advertising in the USA and France by analyzing a real data sample with more than 1.2 million transactions using partial least squares and structural equation modeling.FindingsIt is found that on‐demand channels have a stronger effect on short‐term success than push‐channels and that this effect is strongly moderated by the culture. It is recommended that spending and efforts in the various advertising channels be adjusted to reflect the product offered and the customers to whom it is offered, as customers in both countries should be targeted by advertising in different ways. The channel effectiveness of affiliate price comparison sites and search engines has significantly different impacts on customer behavior in the USA and France.Originality/valueUntil now, most companies have utilized a suboptimal allocation of resources to advertising channels because of missing and misleading data. Focusing on this problem, the paper suggests that advertisers apply the methodology to identify the total effect of clicks in each advertising channel. Combining these total effects with the associated costs allows practitioners to optimize their online advertising spending.

Estrogen Implants: Embodiments of Deeper Problems in the Marketing of Drugs

Estrogen Implants: Embodiments of Deeper Problems in the Marketing of Drugs

The frustrated reviewer — Recurrent failures in manuscripts describing validation of quantitative TLC/HPTLC procedures for analysis of pharmaceuticals

Analytical procedures to be used in pharmaceutical quality control have to be validated strictly in accordance with highly formalized standards and guidance. Manuscripts submitted for publication presenting new procedures must therefore describe the corresponding validation characteristics and the validation approach and procedure accordingly. Interestingly, many of these manuscripts and — what is worse — already published (and therefore accepted) articles in various periodicals are characterized by several typical methodological failures and misconceptions — even though authors have regularly been informed of such mistakes in the hope they can be avoided. The corresponding ICH guideline seems to be well-known, and is frequently cited in these manuscripts, but to some extent is not fully understood and is even partially neglected. In this paper the authors present a collection of typical failures, misconceptions, and misleading data captured as reviewers and readers of published articles over the last two...

Predicting Bone Mass in College Aged Female Gymnasts

Achieving peak bone mass in a female's life is imperative to avoid osteoporotic fractures. According to the National Osteoporosis Foundation, about 85-90% of a females bone mass will be developed by the age of 18. There are several lifestyle and behavioral characteristics that are well documented to be detrimental to peak bone mass development including excessive alcohol consumption and smoking. Less documented are the activities, such as motor activity, that have positive effects on bone mineral density. PURPOSE: The purpose of this study is to see if body weight and muscular strength are valid predictors of bone mineral density in college aged female gymnasts. METHODS: Ten female athletes participated in the study with mean (± SD) age and body weight at 20.15 ± 1.49 yr. and 131.39 ± 14 pounds. All athletes were tested on two days. Day one consisted of bone density scans with height and weight measures taken prior to the scan. Day two consisted of a vertical power test, isokinetic leg strength, and horizontal power test. RESULTS: A multiple regression analysis was used with isokinetic strength of the dominant leg at 60°/second and body weight as the predictor variables regressing on the criterion variable, bone mineral density. Statistical significance was set at a =.05. The output was analyzed for influential data points using leverage (hi >.60) and Cook's D to determine if there were any misleading data. Leverage and Cook's D both indicated that there were not influential outliers in the data. Results indicated that significant differences existed; F (2, 9) = 5.45, p <.05 and that the predictors accounted for over half of the variance in bone mineral density (R2 =.61). Follow up analysis indicated that neither muscle strength, F (1, 9) = 4.86, p =.06, or body weight, F (1, 9) =.50, p =.50 were individually significant. The semi-partial squared correlations revealed that isokinetic strength accounted for 27% of the variance, (b =.64, p =.06), whereas body weight accounted for 3%, (b =.21, p =.50). CONCLUSION: Muscle strength and body weight are predictors of bone mineral density in college aged female gymnasts, with muscular strength accounting for more of the variance.

Challenges that limit meaningful use of health information technology

Health information technology (HIT) is perceived as an essential component for addressing inefficiencies in healthcare. Without understanding the challenges that limit meaningful use of HIT, there is a high chance that institutions will convert complex paper-based systems to expensive digital chaos. Clinical information systems do not communicate with each other automatically because integration of existing data standards is lacking. Data standards for medical specialties need further development. Database architectures are often designed to support single clinical applications and are not easily modified to meet the enterprise-wide needs desired by all end-users. Despite the improvements in charge capture and better access to health information the realized savings and impact on patient throughput is not enough to cover the cost of the technology, maintenance, and support. HIT is necessary for improved quality of care but it increases the cost of doing business. Poor user interface and system design hinders clinical workflow and can result in wasted time, poor data collection, misleading data analysis, and potentially negative clinical outcomes. Healthcare organizations have little recourse if a vendor fails to deliver as intended once the vendor's system becomes embedded into the organization. Decisions on technology acquisitions and implementations are often made by individuals or groups that lack clinical informatics expertise. Government incentives to increase HIT will likely result in a more computerized clinical environment. Understanding the challenges can help avoid costly mistakes. The future looks promising but caution is warranted, as achievement of full benefits of HIT requires addressing significant challenges.