Lessons of ALS imaging: Pitfalls and future directions - A critical review.
Ontology highlight
ABSTRACT: Background
While neuroimaging in ALS has gained unprecedented momentum in recent years, little progress has been made in the development of viable diagnostic, prognostic and monitoring markers.Objectives
To identify and discuss the common pitfalls in ALS imaging studies and to reflect on optimal study designs based on pioneering studies.Methods
A "PubMed"-based literature search on ALS was performed based on neuroimaging-related keywords. Study limitations were systematically reviewed and classified so that stereotypical trends could be identified.Results
Common shortcomings, such as relatively small sample sizes, statistically underpowered study designs, lack of disease controls, poorly characterised patient cohorts and a large number of conflicting studies, remain a significant challenge to the field. Imaging data of ALS continue to be interpreted at a group-level, as opposed to meaningful individual-patient inferences.Conclusions
A systematic, critical review of ALS imaging has identified stereotypical shortcomings, the lessons of which should be considered in the design of future prospective MRI studies. At a time when large multicentre studies are underway a candid discussion of these factors is particularly timely.
SUBMITTER: Bede P
PROVIDER: S-EPMC3950559 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:In this review, we address selected areas that are central to the state-of-the-art of cancer prevention science. The emphasis on prevention as a viable and critical approach to decreasing cancer mortality has gained traction in recent years, evidenced by its inclusion in the US Vice President's Cancer Initiative (also termed 'Moonshot'). Cancer prevention occurs by arresting, slowing down, or reversing the carcinogenic process before invasion into surrounding tissue or by avoiding or blocking causative exposure. An important challenge is to identify individuals who will benefit most from preventive interventions with the least possible harm. Preventive interventions range from avoiding known carcinogens (e.g., tobacco or asbestos) to intervening with anticarcinogenic strategies (behavioral modifications , such as diet and exercise; medications; nutritional agents; and vaccination against causative agents). Here, we focus on active intervention with measures involving pharmaceutical and immunological agents.
| S-EPMC5271581 | biostudies-literature
Project description:A clear rationale can be made for promoting long-term regular physical activity (PA), yet despite some attempts to operationalize "maintenance," no robust definition has been agreed upon, beyond arbitrary time frames of regular PA. This has likely impaired the advancement of theory and practice. The purpose of this critical narrative review was to first overview the conception of maintenance and co-requisite theoretical constructs in theories used in PA research. Our subsequent aims were to engage in a critical analysis of this literature to propose a working definition of PA maintenance followed by recommendations for future research. Relevant behavioral theories were parsed for references to maintenance or maintenance-specific constructs and constructs most likely associated with maintenance were overviewed from a recent systematic review. Based on this information, we suggest PA maintenance be operationalized as a process marked by a shift in the mechanisms of action determining behavioral performance, that engender greater perceived behavioral enactment efficiency. We suggest that maintenance should not be considered an absolute state of behavioral performance (e.g., a stage), as some constructs that were critical to behavioral performance during initiation will still be critical during PA continuation. Based on this definition, we propose a method of falsifiability hypothesis testing of theoretical constructs that may determine the maintenance process. Finally, the review concludes with suggestions for future research using this operationalization of maintenance including measure development, tests of latency to reach the peak maintenance process, validating constructs critical to determining maintenance, exploration of the contextual and individual moderators of maintenance formation, and the development of an omnibus dynamic model of initiation, continuation, and maintenance in PA behavior change.
| S-EPMC8450373 | biostudies-literature
Project description:The extant literature documents burden among caregivers of patients undergoing a hematopoietic stem cell transplantation (HSCT), but little is known about the burden of caregivers of patients receiving outpatient and homebound HSCTs. This scoping study sought to evaluate what is known about the burden of the increasing number of adult caregivers of patients receiving outpatient HSCTs and to create practice guidelines for how to best support this vulnerable group. Online databases were searched for studies that evaluated caregiver burden in adult caregivers of HSCT patients since 2010 (the publication date of the most recent systematic review on HSCT caregiver burden). Of the 1271 articles retrieved, 12 met the inclusion criteria, though none specifically examined outpatient or homebound caregivers. Overall, studies corroborated existing literature on the experience of significant burden among HSCT caregivers across the HSCT trajectory, and highlighted the emotional costs of outpatient transplants on caregivers and the need to identify caregivers at high risk for burden early in the transplant process. Future studies of outpatient caregivers should include a comprehensive assessment of burden and seek to identify points along the transplant trajectory at which caregivers are at particular risk for negative outcomes and when intervention is most appropriate.
| S-EPMC5564416 | biostudies-other
Project description:Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder affecting upper and lower motor neurons, with death resulting mainly from respiratory failure three to five years after symptom onset. As the exact underlying causative pathological pathway is unclear and potentially diverse, finding a suitable therapy to slow down or possibly stop disease progression remains challenging. Varying by country Riluzole, Edaravone, and Sodium phenylbutyrate/Taurursodiol are the only drugs currently approved in ALS treatment for their moderate effect on disease progression. Even though curative treatment options, able to prevent or stop disease progression, are still unknown, recent breakthroughs, especially in the field of targeting genetic disease forms, raise hope for improved care and therapy for ALS patients. In this review, we aim to summarize the current state of ALS therapy, including medication as well as supportive therapy, and discuss the ongoing developments and prospects in the field. Furthermore, we highlight the rationale behind the intense research on biomarkers and genetic testing as a feasible way to improve the classification of ALS patients towards personalized medicine.
| S-EPMC10252394 | biostudies-literature
Project description:Our understanding of fragile X syndrome (FXS) pathophysiology continues to improve and numerous potential drug targets have been identified. Yet, current prescribing practices are only symptom-based in order to manage difficult behaviors, as no drug to date is approved for the treatment of FXS. Drugs impacting a diversity of targets in the brain have been studied in recent FXS-specific clinical trials. While many drugs have focused on regulation of enhanced glutamatergic or deficient GABAergic neurotransmission, compounds studied have not been limited to these mechanisms. As a single-gene disorder, it was thought that FXS would have consistent drug targets that could be modulated with pharmacotherapy and lead to significant improvement. Unfortunately, despite promising results in FXS animal models, translational drug treatment development in FXS has largely failed. Future success in this field will depend on learning from past challenges to improve clinical trial design, choose appropriate outcome measures and age range choices, and find readily modulated drug targets. Even with many negative placebo-controlled study results, the field continues to move forward exploring both the new mechanistic drug approaches combined with ways to improve trial execution. This review summarizes the known phenotype and pathophysiology of FXS and past clinical trial rationale and results, and discusses current challenges facing the field and lessons from which to learn for future treatment development efforts.
| S-EPMC5467059 | biostudies-literature
Project description:Due to the rapid increase in the availability of patient data, there is significant interest in precision medicine that could facilitate the development of a personalized treatment plan for each patient on an individual basis. Radiation oncology is particularly suited for predictive machine learning (ML) models due to the enormous amount of diagnostic data used as input and therapeutic data generated as output. An emerging field in precision radiation oncology that can take advantage of ML approaches is radiogenomics, which is the study of the impact of genomic variations on the sensitivity of normal and tumor tissue to radiation. Currently, patients undergoing radiotherapy are treated using uniform dose constraints specific to the tumor and surrounding normal tissues. This is suboptimal in many ways. First, the dose that can be delivered to the target volume may be insufficient for control but is constrained by the surrounding normal tissue, as dose escalation can lead to significant morbidity and rare. Second, two patients with nearly identical dose distributions can have substantially different acute and late toxicities, resulting in lengthy treatment breaks and suboptimal control, or chronic morbidities leading to poor quality of life. Despite significant advances in radiogenomics, the magnitude of the genetic contribution to radiation response far exceeds our current understanding of individual risk variants. In the field of genomics, ML methods are being used to extract harder-to-detect knowledge, but these methods have yet to fully penetrate radiogenomics. Hence, the goal of this publication is to provide an overview of ML as it applies to radiogenomics. We begin with a brief history of radiogenomics and its relationship to precision medicine. We then introduce ML and compare it to statistical hypothesis testing to reflect on shared lessons and to avoid common pitfalls. Current ML approaches to genome-wide association studies are examined. The application of ML specifically to radiogenomics is next presented. We end with important lessons for the proper integration of ML into radiogenomics.
| S-EPMC6021505 | biostudies-literature
Project description:BACKGROUND:Schizophrenia is associated with increased physical morbidity and early mortality, suggesting that the aging process may be accelerated in schizophrenia. However, the biological underpinnings of these alterations in aging in schizophrenia are unclear. METHOD:We conducted a detailed search of peer-reviewed empirical studies to evaluate evidence for accelerated biological aging in schizophrenia based on systemic, age-related biomarkers. We included studies that investigated differences between persons with schizophrenia and healthy comparison subjects in levels of biomarkers known to be associated with aging and examined the relationship of these biomarkers to age in the 2 groups. RESULTS:Forty-two articles that met our selection criteria were reviewed. Nearly 75% reported abnormal biomarker levels among individuals with schizophrenia, including indices of inflammation, cytotoxicity, oxidative stress, metabolic health, gene expression, and receptor/synaptic function, with medium to large effect sizes reported in many studies. Twenty-nine percent of the studies observed differential age-related decline in schizophrenia. Markers of receptor/synaptic function and gene expression were most frequently differentially related to age in schizophrenia. Schizophrenia patients with greater disease severity and longer illness duration exhibited higher levels of inflammatory and oxidative stress biomarkers and shorter telomere length. CONCLUSIONS:Most studies show biomarker abnormalities in schizophrenia, and there is some suggestion for accelerated aging. Although definitive interpretation is limited by cross-sectional design of the published reports, findings in the area of gene expression and synaptic function are promising and pave the way for future longitudinal studies needed to fully test this hypothesis.
| S-EPMC5815075 | biostudies-literature
Project description:Since the outbreak of COVID-19, buildings that provide improved performance have aroused extensive discussion. Nowadays, the connotation of healthy building is becoming complex, performance metrics for healthy buildings vary significantly from different regions in the world and there may be information asymmetry among stakeholders. Consequently, building health performance cannot be effectively achieved. However, previous studies have launched extensive reviews on green building, and there remains a lack of comprehensive and systematic reviews on healthy buildings. To address the above issues, therefore, this research aims to (1) conduct a thorough review of healthy building research and reveal its nature; and (2) identify the current research gaps and propose possible future research directions. Content analysis using NVivo were applied to review 238 relevant publications. A DNA framework of healthy buildings, which clarifies the characteristics, triggers, guides and actions, was then constructed for better understanding of the nature of them. Subsequently, the application of DNA framework and the directions of future research were discussed. Six future research directions were finally recommended, including life-cycle thinking, standard systems improvement, policies & regulations, awareness increase, healthy building examination, and multidisciplinary integration. This research differs from previous ones because it painted a panorama of previous healthy building research. Findings of this research contribute to reveal knowledge map of healthy buildings, guide researchers to fill existing knowledge gaps, provide a standardized platform for healthy building stakeholders, and promote high-quality development of healthy buildings.
| S-EPMC10280327 | biostudies-literature
Project description:Inferior vena cava filters have been placed in patients for decades for protection against pulmonary embolism. The widespread use of filters has dramatically increased owing at least in part to the approval of retrievable vena cava filters. Retrievable filters have the potential to protect against pulmonary embolism and then be retrieved once no longer needed to avoid potential long-term complications. There are several retrievable vena cava filters available for use. This article discusses the different filter designs as well as the published data on these available filters. When selecting a filter for use, it is important to consider the potential short-term complications and the filters' window for retrieval. Understanding potential long-term complications is also critical, as these devices are approved for permanent placement and many filters are not retrieved. Finally, this article will address research into new designs that may be the future of vena cava filtration.
| S-EPMC4862852 | biostudies-literature
Project description:Background: In November 2019, the IWill gender equity pledge campaign called individuals in a health sciences university to make public pledges for gender equity and fostered meaningful dialog to alter mental models and power dynamics. Over 1400 staff, faculty, and students chose 1 of 18 pledges or created their own. Methods: A follow-up, mixed-methods survey was sent to 1405 participants in July 2020. Results: Fifty-six percent (n = 769) responded. Over 70% endorsed fulfilling their pledge and believed they had the power to promote equity. Men were significantly more likely to endorse fulfilling their pledge, and men and learners endorsed having the power to create change at significantly higher rates than women. Key barriers included time, support for completion, and nonconducive culture or hierarchy. Key supports included personal reminders, self-reflection, and support from a partner, community, or leader. Top reasons for participation in the campaign included fairness or justice, being part of a community, team diversity as an inherent good, and the sense that the Medical College of Wisconsin's (MCW) should be a leader in gender equity. Conclusion: The IWill campaign successfully encouraged faculty, staff, and learners to reflect upon and engage in equity work. Key learnings included the need to streamline administrative support while building a sense of community around equity, and the further work needed to engage leaders and directly support not just individual but also departmental and institutional efforts in gender equity.
| S-EPMC10240325 | biostudies-literature