Scientific Questions Research Articles

Timing of puberty suppression in transgender adolescents and sexual functioning after vaginoplasty.

Sexual function in transgender adolescents after puberty suppression has been a topic of recent clinical and scientific questions. This study aimed to explore the long-term effects of early treatment with puberty suppression on sexual functioning of transfeminine individuals after vaginoplasty. This retrospective cohort study included 37 transfeminine individuals treated with a gonadotropin-releasing hormone agonist (puberty suppression), estrogen, and vaginoplasty (penile inversion technique or intestinal vaginoplasty) at the Center of Expertise on Gender Dysphoria in Amsterdam, the Netherlands, between 2000 and 2016. Experiences regarding sexual functioning and difficulties were assessed with a self-developed questionnaire ~1.5years after genital gender-affirming surgery and compared between early (Tanner stage G2-3) and late (Tanner stage G4-5) treatment with puberty suppression. Following surgery, 91% of transfeminine individuals was able to experience sexual desire, 86% experienced arousal, and 78% could attain an orgasm. Seventy-five percent of transfeminine individuals who had not experienced an orgasm pre-surgery were able to experience one post-surgery. Of all participants, 62% reported having tried penile-vaginal intercourse post-surgery. The majority reported the presence of one or multiple sexual challenges. There were no significant differences in postoperative sexual function or sexual difficulties between groups treated with early versus late puberty suppression. With these findings, more adequate and tailored information on the expected effects of early endocrine gender-affirming treatment (including puberty suppression) can be given by healthcare professionals. This is the first study that has assessed sexual functioning of transgender individuals treated with puberty suppression, and has differentiated between the pubertal stage at treatment initiation. Limitations were the small cohort size and retrospective study design. This study focuses on sexual functioning, however, it is important to realize sexual wellbeing is multifactorial and encompasses more than genital functioning or the ability to have certain sexual experiences. This study found that post-vaginoplasty transfeminine individuals after both early and late suppression of puberty have the ability to experience sexual desire and arousal, and to achieve orgasms. Outcomes are comparable to previous findings in those who started treatment in adulthood.

Laser ablation inductively coupled plasma mass spectrometry measurements for high-resolution chemical ice core analyses with a first application to an ice core from Skytrain Ice Rise (Antarctica)

Abstract. Conventional methods of inorganic impurity analysis do not provide high enough depth resolution for many scientific questions in ice core science. In this study, we present a setup of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for high-resolution glacier ice impurity analysis to the sub-millimetre scale. This setup enables ice core chemical impurity analysis to a depth resolution of ∼182 µm while consuming only very small amounts of ice. The system performs simultaneous analysis of sodium, magnesium and aluminium incorporated in the ice matrix. In this case study within the framework of the WACSWAIN (WArm Climate Stability of the West Antarctic Ice Sheet in the last INterglacial) project, our method is applied to a selection of samples from the Skytrain ice core (West Antarctica) over a total length of 6.7 m consisting of about 130 single samples. The main goal of this study is to use the new LA-ICP-MS method to extract meaningful climate signals on a depth resolution level beyond the limits of continuous-flow analysis (CFA). A comparison between low-resolution CFA data and the high-resolution LA-ICP-MS data reveals generally good agreement on the decimetre scale. Stacking of parallel laser measurements together with frequency analysis is used to analyse the high-resolution LA-ICP-MS data at millimetre resolution. Spectral analysis reveals that despite effects of impurity accumulation along ice crystal grain boundaries, periodic concentration changes in the Skytrain ice core on the millimetre scale can be identified in ice from 26.8 ka (kiloyears before present, i.e. 1950 CE). These findings open new possibilities for climate data interpretation with respect to fast changes in the last glacial period and beyond, for example within the Beyond EPICA oldest-ice project.

An Introduction to Longitudinal Synthetic Cohorts for Studying the Life Course Drivers of Health Outcomes and Inequalities in Older Age

Abstract Recent Findings Research on the drivers of health across the life course would ideally be based in diverse longitudinal cohorts that repeatedly collect detailed assessments of risk factors over the full life span. However, few extant data sources in the US possess these ideal features. A “longitudinal synthetic cohort”—a dataset created by stacking or linking multiple individual cohorts spanning different but overlapping periods of the life course—can overcome some of these challenges, leveraging the strengths of each component study. This type of synthetic cohort is especially useful for aging research; it enables description of the long-term natural history of disease and novel investigations of earlier-life factors and mechanisms shaping health outcomes that typically manifest in older age, such as Alzheimer’s disease and related dementias (ADRD). Purpose of Review We review current understanding of synthetic cohorts for life course research. We first discuss chief advantages of longitudinal synthetic cohorts, focusing on their utility for aging/ADRD research to concretize the discussion. We then summarize the conditions needed for valid inference in a synthetic cohort, depending on research goals. We end by highlighting key challenges to creating longitudinal synthetic cohorts and conducting life course research within them. Summary The idea of combining multiple data sources to investigate research questions that are not feasible to answer using a single cohort is gaining popularity in epidemiology. The use of longitudinal synthetic cohorts in applied research—and especially in ADRD research—has been limited, however, likely due to methodologic complexity. In particular, little guidance and few examples exist for the creation of a longitudinal synthetic cohort for causal research goals. While building synthetic cohorts requires much thought and care, it offers tremendous opportunity to address novel and critical scientific questions that could not be examined in a single study.

Community-based reconstruction and simulation of a full-scale model of the rat hippocampus CA1 region.

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.

Modular shadowgraph imaging for zooplankton ecological studies in diverse field and mesocosm settings

AbstractVarious iterations of shadowgraph imaging have been used to quantify zooplankton in situ with high spatial resolution. Because these systems can image relatively large volumes of water, they are especially useful for resolving less common meso‐ or macrozooplankton taxa (< 50 ind. m−3), such as larval fishes and gelatinous animals. However, larger volume imagers are typically integrated with heavy towed vehicles and deployed from research vessels, which introduces high costs and limits sampling approaches. Here we demonstrate that versatile configurations of shadowgraph imaging, including modular benchtop, handheld, and towed, compact vehicle systems (along with customizable software), allow for tailoring sampling to a variety of marine and freshwater settings (including mesocosms). These systems encompass a suite of possible architectures, designed for adapting the imaging depth of field, acquisition rates, sensor configuration, and deployment method to fit a wide range of sampling protocols, with high vertical resolution (~ 5 cm) and adequate taxonomic capabilities for > 0.5 mm organisms. The benchtop system facilitates an interactive approach to observe and quantify zooplankton behaviors and optical properties. Video footage from the benchtop system generates thousands of regions of interest min−1 for target organisms with variable orientations and swimming postures. When used in conjunction with in situ imaging, the benchtop system can build large machine learning training libraries targeted toward rare or morphologically diverse zooplankton, which often includes the larval stages of economically valuable taxa. These modular hardware and software components increase affordability and versatility while broadening the scope of scientific questions addressed by plankton imaging systems.

Dos and don'ts for conducting mediation analysis: A commentary with practical tips to avoid common problems.

Purpose: Mediation analyses allow for exploration of causal mechanisms that explain how a predictor is related to an outcome. Tests of mediation are fundamental to addressing some of the most consequential questions in rehabilitation science. In recent decades, the development of easy-to-use analytical tools has made conducting statistical tests of mediation more accessible to researchers. Unfortunately, there are persistent problems in the conceptual underpinning of many tests of mediation. Even in cases where the statistical analyses are correctly run, problems with the underlying rationale for the mediational analysis will render the results inconsequential, in the best case, or misleading, in the worst case. Method: In this commentary, I summarize the uses of mediation analysis and through a series of six main types of errors provide practical, plain language guidance ("Dos and Don'ts") for conducting a conceptually robust mediation analysis. Results: The "Dos and Don'ts" laid out in this commentary highlight that there are persistent issues with lack of understanding of mediation, confusion about the differences between moderation, mediation, and covariates, lack of strong theoretical justification for mediation, and lack of attention to methodological issues (e.g., measurement) in many mediation analyses. Conclusions: Promoting the use of mediation analysis in rehabilitation research will advance theory and effective practice in our field. Researchers undertaking mediation analysis are encouraged to prioritize developing a strong theoretical framework that justifies use of mediation analysis, ensuring study methodology supports and enables tests of mediation, as well emphasizing a strong statistical approach to conducting the test of mediation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assess of students’ Knowledge Concerning Effect of Lifestyle on Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS), also known as Stein-Leventhal syndrome, is an endocrine disorder that affects 15% to 20% of women of reproductive age and involves the presence of multiple follicular cysts on one or both ovaries. This study was conducted to assess the knowledge about PCOS, effects of lifestyle habits on PCOS and knowledge of diverse treatment methods to reduce the risks of the syndrome.180 female students from three colleges were participate a questionnaire include demographic information of students and scientific questions concerning PCOS, Among the 180 female students whose knowledge was evaluated about the effect of lifestyle on polycystic ovary syndrome, (32%) of the participants had a good knowledge rate, (53%) of them had a moderate knowledge rate, and (15%) had a poor knowledge rate.

Comparative case study of evolutionary insights and floral complexity in key early-diverging eudicot Ranunculales models

Famously referred to as “Darwin’s abominable mystery,” the rapid diversification of angiosperms over the last ~140 million years presents a fascinating enigma. This diversification is underpinned by complex genetic pathways that evolve and rewire to produce diverse and sometimes novel floral forms. Morphological innovations in flowers are shaped not only by genetics but also by evolutionary constraints and ecological dynamics. The importance of model organisms in addressing the long-standing scientific questions related to diverse floral forms cannot be overstated. In plant biology, Arabidopsis thaliana, a core eudicot, has emerged as a premier model system, with its genome being the first plant genome to be fully sequenced. Similarly, model systems derived from crop plants such as Oryza sativa (rice) and Zea mays (maize) have been invaluable, particularly for crop improvement. However, despite their substantial utility, these model systems have limitations, especially when it comes to exploring the evolution of diverse and novel floral forms. The order Ranunculales is the earliest-diverging lineage of eudicots, situated phylogenetically between core eudicots and monocots. This group is characterized by its exceptional floral diversity, showcasing a wide range of floral morphologies and adaptations that offer valuable insights into the evolutionary processes of flowering plants. Over the past two decades, the development of at least five model systems including, Aquilegia, Thalictrum, Nigella, Delphinium and Eschscholzia within the Ranunculales order has significantly advanced our understanding of floral evolution. This review highlights the conservation and divergence of floral organ identity programs observed among these models and discusses their importance in advancing research within the field. The review also delves into elaborate petal morphology observed in Aquilegia, Nigella, and Delphinium genera, and further discusses the contributions, limitations, and future research directions for Ranunculales model systems. Integrating these diverse models from the early-diverging eudicot order has enhanced our understanding of the complex evolutionary pathways that shape floral diversity in angiosperms, bridging the knowledge gaps essential for a comprehensive understanding of floral evolution.

Chasing Shadows: How Implausible Assumptions Skew Our Understanding of Causal Estimands

The ICH E9 (R1) addendum on estimands, coupled with recent advancements in causal inference, has prompted a shift towards using model-free treatment effect estimands that are more closely aligned with the underlying scientific question. This represents a departure from traditional, model-dependent approaches where the statistical model often overshadows the inquiry itself. While this shift is a positive development, it has unintentionally led to the prioritization of an estimand’s ability to perfectly answer the key scientific question over its practical learnability from data under plausible assumptions. We illustrate this by scrutinizing assumptions in the recent clinical trials literature on principal stratum estimands, demonstrating that some popular assumptions are not only implausible but often inevitably violated. We advocate for a more balanced approach to estimand formulation, one that carefully considers both the scientific relevance and the practical feasibility of estimation under realistic conditions.

Optimal designs for testing pairwise differences: A graph‐based game theoretic approach

AbstractIn a variety of experimental settings there is an interest in comparing pairs–of–treatments. Such experiments usually address one of the following two scientific questions: (1) is there a difference within any of the selected pairs of treatments? or (2) is there a difference within all of the selected pairs of treatments? In this article, we propose max–min optimal designs for testing the above hypotheses using a graph‐based game theoretic approach. Some of the max–min designs obtained are well known, but not recognized as optimal, others are novel and provide an improvement over naive designs.

Recording diagnostic conversations for communication research purposes in pediatric leukemia.

Recordings of patient-doctor interactions is a recommended method in communication research. However, concerns are expressed regarding audio-recording of conversations with vulnerable patients. Our study examined experiences of children, parents, and oncologists with recording diagnostic conversations in the pediatric acute leukemia setting. Results show that recording conversations is generally well received by virtually all children and parents. Pediatric oncologists seem to overestimate the expected emotional burden for children and parents, which may lead to gatekeeping by professionals. This in turn may lead to a decrease in patient autonomy and research quality when addressing relevant questions in communication science.

Thinking Skills Level Classification of Scientific Questions Using Bidirectional LSTM

Thinking Skills Level Classification of Scientific Questions Using Bidirectional LSTM

Navigating investigator-initiated clinical trials: A call for guidelines & monitoring frameworks from an Indian context

Investigator-initiated clinical trials – also known as non-regulatory or academic clinical trials, are conducted by investigators from academia or research organizations. They usually aim to address scientific questions with insufficient commercial implications and generate real-world applicable solutions, unlike trials sponsored by the pharmaceutical industry which are primarily focused on marketing approval of products that have a commercial value. For the trial results to be credible, adhering to robust methodology and the highest quality standards is paramount. Currently, investigator-initiated clinical trials in India are beyond the purview of the national regulatory authority. They are guided mainly by the National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, 2017 published by Indian Council of Medical Research. They lack an accepted framework for review, conduct, monitoring, reporting of adverse events, and participant compensation. Considering this scenario, we discuss the challenges faced in an investigator initiated clinical trial and explore plausible solutions.

FIB/SEM serial sectioning as a versatile tool for microstructural analysis

Abstract FIB/SEM tomography is a serial sectioning method in which the cross-sectional area of the sample is stepwise removed with a focused ion beam (FIB) and the exposed cross-sectional area is imaged with a scanning electron microscope (SEM). All imaging techniques of the SEM can be used, which allows the application to a wide range of materials science questions. On the one hand, resolutions of a few nm can be achieved, and on the other hand, volumes with edge lengths of 100 μm and more can be examined. This article gives an overview of the current state of the art and the practical implementation of FIB/ SEM serial sectioning. The special aspects of the integration of energy dispersive X-ray spectroscopy (EDS) and electron backscatter diffraction (EBSD) are also discussed.

Uneasiness in interdisciplinary research and the importance of metaphors: A case story on building an interdisciplinary chronic pain research team

Interdisciplinary research is increasingly recognized as a key method to tackle complex societal challenges and stimulate creativity to find innovative solutions. Our key goal when starting our collaboration was to come to innovative ways of treating chronic pain. An ambitious goal that requires out-of-the-box and high-risk-high-gain research. However, interdisciplinary research in practice can be uneasy and will not always be successful. This paper describes a case story focussing on the challenges we faced building an interdisciplinary team. One of the most important lessons is that researchers from different disciplines may think they speak a universal ‘language of science’, but a thorough understanding of each other's ways of working, research paradigms, methods, and concepts is necessary before they can start working together on solving scientific questions. In fact, if researchers cannot understand each other's language, they cannot expect patients to understand scientific language either. Lastly, for academics to engage with a non-scientific audience and vice-versa, we need to find and create places to meet and find ways to interact effectively. Language is the medium through which all these interactions take place. It is therefore essential that language takes a central place in the process of collaboration across disciplines, interdisciplinary research, patient participation and public engagement. In this case story, we share our experiences in creating a common language, summarized in five steps (1: creating the team; 2: metaphor-forced introduction to disciplines; 3: creating common ground; 4: outreach; 5: integration). Metaphors play an important role in this process. We will demonstrate how we reflectively progressed through these steps while enhancing interdisciplinarity, (scientific) innovation and public engagement. This five-step journey can be used as a process-tool for any other high-risk-high-gain research team seeking to innovate through interdisciplinarity – with the risk of becoming a brilliant failure.

On the applicability of low-cost GNSS antennas to precise surveying applications

Abstract This study addresses the scientific question of the applicability of low-cost antennas to the most precise GNSS applications. First of all, we inspect the implications of the availability and quality of low-cost antenna PCC models for precise positioning. From this point of view, we analyze the selected performance indicators of multi-constellation positioning with the representative set of low-cost mass-market GNSS receiver antennas. The processing strategy was based on the relative positioning model, considered the most reliable and precise one. To isolate the antenna-related errors from atmospheric propagation ones, we conducted an experiment based on an ultra-short baseline. As the main indications of low-cost antenna performance, we considered distance and height residuals, defined as the difference between benchmarks and the retrieved from GNSS measurements. We found that the low-cost antenna's PCV effect may significantly affect the final results. On the other hand, the results obtained using certain configurations of low-cost antennas were characterized by only slightly higher standard deviations and discrepancies with respect to benchmark values than those obtained with surveying or geodetic equipment. We identify several sets of low-cost antennas where distance residuals do not exceed 4 mm and height residuals do not exceed 6 mm, which shows the low-cost antenna performance comparable to those achieved using high-grade antennas. On this basis, we conclude that selected low-cost antennas can meet the requirements of high-precision surveying applications.

Establishing correct concept meanings in psychology: Why should we care and how can we do it?

The purpose of this article was to address and to propose answers to three basic questions in psychological science. (a) Why should we care about carefully and rigorously establishing correct meanings for the concepts we employ in our research and clinical work, especially in those cases where foundational concepts such as "behavior," "mental disorder," and "personality" are concerned? (b) How can we move beyond meanings grounded in little more than relatively meager armchair intuition to ones grounded in ways that strongly justify their acceptance as correct and thus might result in consistency and uniformity in the field regarding their meanings? (c) Aside from the standard practices of providing definitions and prototypes, what are some other forms that concept formulation takes in other sciences and could take in psychological science, that is, other means of capturing and demarcating the domains of reference of our concepts? (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Shabana Khan.

"A turning point in my career was working on silylene chemistry during my postdoctoral research, which provided a vision of utilizing low-valent compounds in different fields of science… I chose my current career path because of the freedom to explore scientific questions alongside young minds…" Find out more about Shabana Khan in her Introducing… Profile.

What is health services research?

In health services research, the health care of the population is examined under everyday conditions. Scientific questions include medical, patient-oriented, system-, performance- and quality-related as well as health economics topics. In health services research, complex interventions, e.g., treatment concepts with multiple therapy components, and/or across multiple sectors, are often implemented. The design of studies in health services research is based on the research question, the setting, and the available data, which can come from avariety of sources.

Advancing the role of real-world evidence in comparative effectiveness research.

Aim: Comparative effectiveness research (CER) is essential for making informed decisions about drug access. It provides insights into the effectiveness and safety of new drugs compared with existing treatments, thereby guiding better healthcare decisions and ensuring that new therapies meet the real-world needs of patients and healthcare systems. Objective: To provide a tool that assists analysts and decision-makers in identifying the most suitable analytical approach for answering a CER question, given specific data availability contexts. Methods: A systematic literature review of the scientific literature was performed and existing regulatory and health technology assessment (HTA) guidance were evaluated to identify and compare recommendations and best practices. Based on this review a methods flowchart that synthesizes current practices and requirements was proposed. Results: The review did not find any papers that clearly identified the most appropriate analytical approach for answering CER questions under various conditions. Therefore, a methods flowchart was designed to inform analyst and decision makers choices starting from a well-defined scientific question. Conclusion: The proposed methods flowchart offers clear guidance on CER methodologies across a range of settings and research needs. It begins with a well-defined research question and considers multiple feasibility aspects related to CER. This tool aims to standardize methods, ensure rigorous and consistent research quality and promote a culture of evidence-based decision-making in healthcare.