Thyroid FNAC cytology: can we do it better?

This article reviews recent developments in thyroid fine needle aspiration cytology (FNAC). While thyroid nodules are common, carcinoma is comparatively rare. Although histological assessment is used in most studies as the benchmark, the differential diagnosis on cytology or histology is not always reproducible. The literature shows wide variations in criteria for inadequate thyroid FNAC and study inclusion or exclusion criteria. In-clinic assessment of specimen adequacy and in-clinic reporting of thyroid FNAC has become popular although the costs and resource implications of in-clinic thyroid FNAC assessment and reporting are substantial. Many centres continue to use conventional techniques although liquid-based cytology and ultrasound-guided FNAC are gaining in popularity. Standardized categorical systems for FNAC reporting can make results easier to understand for clinicians and give clear indications for therapeutic action. Multidisciplinary case review is also essential, especially when there is diagnostic uncertainty. While currently of limited use, molecular pathology testing holds out some promise for the future.     

Addressing delayed case reporting in infectious disease forecast modeling

Infectious disease forecasting is of great interest to the public health community and policymakers, since forecasts can provide insight into disease dynamics in the near future and inform interventions. Due to delays in case reporting, however, forecasting models may often underestimate the current and future disease burden.In this paper, we propose a general framework for addressing reporting delay in disease forecasting efforts with the goal of improving forecasts. We propose strategies for leveraging either historical data on case reporting or external internet-based data to estimate the amount of reporting error. We then describe several approaches for adapting general forecasting pipelines to account for under- or over-reporting of cases. We apply these methods to address reporting delay in data on dengue fever cases in Puerto Rico from 1990 to 2009 and to reports of influenza-like illness (ILI) in the United States between 2010 and 2019. Through a simulation study, we compare method performance and evaluate robustness to assumption violations. Our results show that forecasting accuracy and prediction coverage almost always increase when correction methods are implemented to address reporting delay. Some of these methods required knowledge about the reporting error or high quality external data, which may not always be available. Provided alternatives include excluding recently-reported data and performing sensitivity analysis. This work provides intuition and guidance for handling delay in disease case reporting and may serve as a useful resource to inform practical infectious disease forecasting efforts.     

River Restoration in Victoria, Australia: Change is in the Wind, and None too Soon

Stream restoration has become a multibillion dollar industry worldwide, yet there are few clear success stories and the scientific basis for effective stream restoration remains uncertain. We compiled data on completed river restoration projects from four management authorities in Victoria, Australia, to examine how the available data could inform the science of restoration ecology in rivers, and thus improve future restoration efforts. We found that existing data sources are limited and much historical information has been lost through industry restructuring and poor data archiving. Examining records for 2,247 restoration projects, we found that riparian management projects were the most common, followed by bank stabilization and in‐stream habitat improvement. Only 14% of the project records indicated that some form of monitoring was carried out. It is evident that overall there is little scientific guidance and little or no monitoring and evaluation of the projects for which we had information. However, recent advances with mandatory, statewide reporting and an increased emphasis on project design and monitoring strongly suggest that the design, implementation, monitoring, and reporting of stream restoration projects have improved in recent years and will continue to do so.     

Trends in the reporting of tagging procedures for fish telemetry studies that have used surgical implantation of transmitters: a call for more complete reporting

The intracoelomic surgical implantation of telemetry transmitters in fish is becoming the “standard” tagging approach for most field telemetry studies. Subsequently, efforts must be made to ensure the welfare of the fish are maintained and that fish do not experience significant mortality or sublethal impairments in health, behavior or physiology as a result of surgical procedures. Therefore, it is essential to adequately report information relating to all aspects of the surgical procedure to enable the reader to make an accurate interpretation of study results. We conducted a quantitative literature review aimed at characterizing trends in data reporting by examining a sample of fish telemetry studies published in peer-reviewed outlets during the last 20 years. We used a repeatability score, based on 16 predetermined criteria, to evaluate the reporting of surgical procedures in telemetry studies. The majority of studies failed to report basic information relating to the surgical procedures used. Repeatability scores were highly variable between studies and ranged from 0–93.8%. No single study provided complete information (mean repeatability score = 50.7%) and repeatability showed no trend over time. Some study information was consistently well reported (e.g. tag size and dimensions, the type of anaesthetic used and the location of incision). In contrast, the type of suture knots, duration or level of anaesthesia and precautions taken to minimize infection were consistently left out of the methods section of most telemetry studies. Our review was confounded by the large proportion of studies that cited other sources for their surgical methods, many of which themselves lacked complete information. We recommend that future electronic tagging studies that involve intracoelomic implantation include the minimum reporting standards presented in this paper. Increasing the detail of reporting will improve the quality of data presented, minimize welfare and ethical concerns and allow transparency for study repeatability.     

Current practices for describing the performance of molecularly imprinted polymers can be misleading and may be hampering the development of the field

A contributing factor to the labored advance of molecularly imprinting as a viable commercial solution to molecular recognition needs is the absence of a standard and robust method for assessing and reporting on molecular imprinted polymer (MIP) performance. The diversity and at times inappropriateness of MIP performance indicators means that the usefulness of the literature back-catalogue, for predicting, elucidating or understanding patterns in MIP efficacy, remains largely inaccessible. We hereby put forward the case that the simple binding isotherm is the most versatile and useful method of assessing and reporting MIP function, allowing direct comparison between polymers prepared and evaluated in different studies. In this study we describe how to correctly plot and interpret a bound / free isotherm and show how such plots can be readily used to predict outcomes, retro-analyze data and optimize experimental design. We propose that by adopting the use of correctly constructed isotherms as the primary form of data representation researchers will enable inter-laboratory comparisons, promote good experimental design and encourage a greater collective understanding of molecular imprinting.     

Quality control for plant metabolomics: reporting MSI-compliant studies

The Metabolomics Standards Initiative (MSI) has recently released documents describing minimum parameters for reporting metabolomics experiments, in order to validate metabolomic studies and to facilitate data exchange. The reporting parameters encompassed by MSI include the biological study design, sample preparation, data acquisition, data processing, data analysis and interpretation relative to the biological hypotheses being evaluated. Herein we exemplify how such metadata can be reported by using a small case study – the metabolite profiling by GC-TOF mass spectrometry of Arabidopsis thaliana leaves from a knockout allele of the gene At1g08510 in the Wassilewskija ecotype. Pitfalls in quality control are highlighted that can invalidate results even if MSI reporting standards are fulfilled, including reliable compound identification and integration of unknown metabolites. Standardized data processing methods are proposed for consistent data storage and dissemination via databases.     

Examining the effects of one- and three-dimensional spatial filtering analyses in magnetoencephalography

Spatial filtering, or beamforming, is a commonly used data-driven analysis technique in the field of Magnetoencephalography (MEG). Although routinely referred to as a single technique, beamforming in fact encompasses several different methods, both with regard to defining the spatial filters used to reconstruct source-space time series and in terms of the analysis of these time series. This paper evaluates two alternative methods of spatial filter construction and application. It demonstrates how encoding different requirements into the design of these filters has an effect on the results obtained. The analyses presented demonstrate the potential value of implementations which examine the timeseries projections in multiple orientations at a single location by showing that beamforming can reconstruct predominantly radial sources in the case of a multiple-spheres forward model. The accuracy of source reconstruction appears to be more related to depth than source orientation. Furthermore, it is shown that using three 1-dimensional spatial filters can result in inaccurate source-space time series reconstruction. The paper concludes with brief recommendations regarding reporting beamforming methodologies in order to help remove ambiguity about the specifics of the techniques which have been used.     

Benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as potential antitrypanosomal drugs. Part 3: Substituents-clustering methodology in the search for new active compounds

The results of a study on the use of Hansch's series design, cluster methodology, for the generation of new benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as antitrypanosomal compounds are described. In vitro activity of these compounds was tested against Tulahuen 2 strain of Trypanosoma cruzi. Clearly, the Hansch methodology allowed identifying two cluster-substituents suitable for further structural modifications. The most effective drugs, derivatives 11, 18, and 21, with 50% inhibitory concentration (IC(50)) of the same order as that of the reference drug, represent an excellent structural point of chemical modifications for the design of future drugs. Preliminary results from the study of the mechanism of action of these benzofuroxans point to perturbation of the mitochondrial electron chain, inhibiting parasite respiration.     

Review: Assessment of completeness of reporting in intervention studies using livestock: an example from pain mitigation interventions in neonatal piglets

Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources.     

A Systematic Composite Service Design Modeling Method Using Graph-Based Theory

The composite service design modeling is an essential process of the service-oriented software development life cycle, where the candidate services, composite services, operations and their dependencies are required to be identified and specified before their design. However, a systematic service-oriented design modeling method for composite services is still in its infancy as most of the existing approaches provide the modeling of atomic services only. For these reasons, a new method (ComSDM) is proposed in this work for modeling the concept of service-oriented design to increase the reusability and decrease the complexity of system while keeping the service composition considerations in mind. Furthermore, the ComSDM method provides the mathematical representation of the components of service-oriented design using the graph-based theoryto facilitate the design quality measurement. To demonstrate that the ComSDM method is also suitable for composite service design modeling of distributed embedded real-time systems along with enterprise software development, it is implemented in the case study of a smart home. The results of the case study not only check the applicability of ComSDM, but can also be used to validate the complexity and reusability of ComSDM. This also guides the future research towards the design quality measurement such as using the ComSDM method to measure the quality of composite service design in service-oriented software system.     

B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumaband implications for study design

B cells are believed to be central to the disease process in systemic lupuserythematosus (SLE), making them a target for new therapeutic intervention. In recentyears there have been many publications regarding the experience in SLE of B-celldepletion utilising rituximab, an anti-CD20 mAb that temporarily depletes B cells,reporting promising results in uncontrolled open studies and in routine clinical use.However, the two large randomised controlled trials in extra-renal lupus (EXPLORERstudy) and lupus nephritis (LUNAR study) failed to achieve their primary endpoints.Based on the clinical experience with rituximab this failure was somewhat unexpectedand raised a number of questions and concerns, not only into the true level ofbenefit of B-cell depletion in a broad population but also how to test the true levelof effectiveness of an investigational agent as we seek to improve the design oftherapeutic trials in SLE. A better understanding of what went wrong in these trialsis essential to elucidate the underlying reasons for the disparate observations notedin open studies and controlled trials. In this review, we focus on various factorsthat may affect the ability to accurately and confidently establish the level oftreatment effect of the investigational agent, in this case rituximab, in the twostudies and explore hurdles faced in the randomised controlled trials investigatingthe efficacy of ocrelizumab, the humanised anti-CD20 mAb, in SLE. Further, based onthe lessons learned from the clinical trials, we make suggestions that could beimplemented in future clinical trial design to overcome the hurdles faced.     

Significant Discovery of Tetrahydrothieno[3,2‐c]pyridine‐2‐carboxamide Analogs as Potent P2Y12 Receptor Antagonists

A series of analogs containing tetrahydrothieno[3,2‐c]pyridine‐2‐carboxamide as a building block with numerous alicyclic and aromatic amines were synthesized. All analogs were characterized by spectral analysis and evaluated for their in vitro antiplatelet activity. 4‐Fluorophenyl amide derivatives (compounds 8 – 11 ) have been found to be most active in the series with respect to prasugrel and aspirin, a third generation antiplatelet agents (P2Y12 receptor antagonists). Docking study also manifested the admirable binding mode of in vitro active compounds 10 and 11 with the target protein. The results may provide a new perception for future pharmacophore with simple design strategy and avoid tedious synthesis of clopidogrel and prasugrel.     

Synthesis and anticonvulsant evaluation of some new 2,3,8-trisubstituted-4(3H)-quinazoline derivatives

A new series of 2,3,8-trisubstituted-4(3H)-quinazoline derivatives were synthesized, evaluated for their anticonvulsant activity against electrically (MES) and chemically (PTZ, picrotoxin and Strychnine) induced seizures and compared with the standard drugs methaqualone and sodium valproate. Compounds 3, 17 and 22 proved to be the most potent compounds of this series with relatively low neurotoxicity and low toxicity in the median lethal dose test as compared with the reference drugs. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs.     

Therapeutic protocol in the treatment of trigeminal neuralgia

The ideal treatment of trigeminal neuralgia is still an open question. A recent large series reporting the results from the three available percutaneous techniques has been reviewed. Fifty consecutive cases, treated from January 1984 to January 1985, are reported. Microcompression was performed as the first approach in all cases. The other techniques were adopted only in case of failure of microcompression.     

The effects of an online learning environment with worked examples and peer feedback on students’ argumentative essay writing and domain-specific knowledge acquisition in the field of biotechnology

Abstract

The present study investigated the effects of an online learning environment supported with worked examples and peer feedback on students’ argumentative essay writing and domain-specific knowledge acquisition in the field of biotechnology. As part of a bigger project, a pre- and post-test study design was used with 45 bachelor students who were randomly grouped in pairs. Students were asked to analyse a case and write an argumentative essay taking into account the advantages and disadvantages of genetically modified organisms. The results showed that the combination of worked examples and peer feedback improve the quality of argumentative essay writing and facilitate the acquisition of domain-specific knowledge. Implications, suggestions, and future research are discussed.