Neuroscience and Neurobiology Commons^™

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Exploring The Effects Of Transcranial Direct Current Stimulation Of The Right Inferior Frontal Gyrus On Inhibitory Control In Posttraumatic Stress Disorder, Colton Rippey

Theses and Dissertations--Psychology

Background: The right inferior frontal gyrus (rIFG) is implicated in stop signal reaction time (SSRT) performance – a common measure of inhibitory control – and emotional expression and control. Individuals with posttraumatic stress disorder (PTSD) exhibit poorer stop SSRT performance, which is associated with rIFG hypoactivity. Neuromodulation of the rIFG with transcranial direct current stimulation (tDCS) can significantly improve inhibitory control and reduce fearful responding to threatening stimuli. Research has yet to test the effects of multifocal tDCS targeting the rIFG on inhibitory control or emotional reactivity in individuals with PTSD.

Methods: The current study aims to examine the impact …

Fiber Photometry Analysis Of Spontaneous Dopamine Signals: The Z-Scored Data Are Not The Data, Conner W. Wallace, Clare Y. Slinkard, Rachael Shaughnessy, Katherine M. Holleran, Samuel W. Centanni, Christopher C. Lapish, Sara R. Jones

Department of Medicine Faculty Publications

Fluorescent sensors have revolutionized the measurement of molecules in the brain, and the dLight dopamine sensor has been used extensively to examine reward- and cue-evoked dopamine release, but only recently has the field turned its attention to spontaneous release events. Analysis of spontaneous events typically requires evaluation of hundreds of events over minutes to hours, and the most common method of analysis, z-scoring, was not designed for this purpose. Here, we compare the accuracy and reliability of three different analysis methods to identify pharmacologically induced changes in dopamine release and uptake in freely moving C57BL/6J mice. The D1-like receptor antagonist …

Key Brain Region Identification In Obesity Prediction With Structural Mri And Probabilistic Uncertainty Aware Model, Walia Farzana, Megan A. Witherow, Ahmed Temtam, Liangsuo Ma, Melanie Bean, F. Gerry Moeller, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Objectives/Goals: Predictive performance alone may not determine a model’s clinical utility. Neurobiological changes in obesity alter brain structures, but traditional voxel-based morphometry is limited to group-level analysis. We propose a probabilistic model with uncertainty heatmaps to improve interpretability and personalized prediction. Methods/Study Population: The data for this study are sourced from the Human Connectome Project (HCP), with approval from the Washington University in St. Louis Institutional Review Board. We preprocessed raw T1-weighted structural MRI scans from 525 patients using an automated pipeline. The dataset is divided into training (357 cases), calibration (63 cases), and testing (105 cases). Our probabilistic model …

Précis Of The Edge Of Sentience: Risk And Precaution In Humans, Other Animals, And Ai, Jonathan Birch

Animal Sentience

We often face grave practical decisions that seem to hinge on whether a system is sentient. This family of cases includes invertebrate animals, people who are unresponsive after brain injury, fetuses, neural organoids, and now AI technologies. We must decide what to do despite ongoing disagreement about the nature of sentience. In our state of uncertainty, we should pragmatically transform the question from “Is it sentient?” to “Is it a sentience candidate, an investigation priority, or neither?”. When a system is a sentience candidate, it is negligent to fail to consider precautions. We should instead evaluate precautions for their proportionality …

Effect Of Family-Centered Care Interventions On Motor And Neurobehavior Development Of Very Preterm Infants: A Systematic Review And Meta-Analysis, Manasa Kolibylu Raghupathy, Shradha S. Parsekar, Shubha R. Nayak, Kalesh M. Karun, Sonia Khurana, Alicia J. Spittle, Leslie Edward S. Lewis, Bhamini Krishna Rao

Rehabilitation Sciences Faculty Publications

Aim

To assess the effectiveness of family-centered care (FCC) interventions on motor and neurobehavior development of very preterm infants.

Method

Randomized and quasi-randomized trials assessing the effect of FCC on motor and neurobehavioral outcomes in very preterm infants (28–32 wk gestation) were included. Five electronic databases and grey literature were searched from January 2010 to August 2022. Two reviewers independently screened the titles/abstracts and full texts, assessed the risk of bias, and extracted data. The Cochrane Risk of Bias 2.0 Tool and GRADE were used for risk and evidence certainty assessments. Meta-analysis or narrative synthesis was performed based on data …

Die Wirkliche Gefahr Liegt In Der Erosion Der Autonomie: Ein E-Mail-Interview Über Kognitive Freiheit Und Die Problematische Nutzung Neuronaler Daten, Nita Farahany, James Kennaway, Bernd Bösel

Faculty Scholarship

In this interview, James Kennaway and Bernd Bösel talk to Nita Farahany about significant themes related to the idea of mind control, as discussed in her book "The Battle for Your Brain" (2023). The book outlines the risks that neurotechnology poses to "cognitive freedom". EEG and EMG data are increasingly used in consumer products, raising concerns about potential misuse. Companies and governments could exploit cognitive biometric data for manipulation or control. Farahany calls for clear legal protections and highlights differences between U.S. and European regulations. She warns of neurotechnological warfare and advocates for global bans. While full mind control remains …

Leveraging Epigenomics And Transcriptomics To Develop High-Dimensional Biomarkers Of Neuroinflammation, Steven C. Pike

Dartmouth College Ph.D Dissertations

Neuroinflammation is a critical physiological phenomenon implicated in most neurological disorders, either as a cause or a consequence of pathology. Our understanding of neuroinflammation is limited by the inability to directly profile the cells of interest. Thus, developing biomarkers of neuroinflammation is clinically urgent as we know neuroinflammation correlates with patient outcomes and treatment success. The recent advances in “omics” technologies, particularly epigenomics and transcriptomics, provides the opportunity for high-dimensional profiling of biospecimens for potential biomarkers. Within this dissertation, I demonstrate that biomarkers obtained from “omics” platforms can detect neuroimmunological phenomena in clinical and preclinical settings. In chapter one, DNA …

Inductions Of Long-Term Potentiation With Biomimetic Electromagnetic Fields In Primary Neurons, Cooper E. Kansala

Theses and Dissertations (Comprehensive)

Endogenous brain rhythms guide neural communication and plasticity, raising the question of whether weak, temporally structured electromagnetic fields (EMFs) that mimic these rhythms can modulate neuronal activity in a targeted, biomimetic manner. This thesis investigates whether patterned EMFs designed to reflect the temporal structure of hippocampal long-term potentiation (LTP) are more effective at inducing neural plasticity than conventional sinusoidal fields or no stimulation at all. Cortical neurons cultured from postnatal rats were exposed to patterned EMFs for 30 minutes and assessed across three distinct experimental domains. In Chapter 2, microelectrode array (MEA) recordings revealed that the LTP-patterned field significantly increased …

Hippocampal Insulin Exists! In Vivo Sampling Methods, Basal Concentrations, Recurrent Hypoglycemia, And Behavioral Extracellular Insulin Responses, Starlette R. Douglass

Electronic Theses & Dissertations (2024 - present)

Insulin has widespread actions within the brain, including energy homeostasis, modulation of feeding, and as a key component of memory processes. Further, brain insulin dysfunction correlates with Alzheimer's disease and other neurodegenerative disorders. To this point, measurement of hippocampal insulin has been limited. Determining in vivo hippocampal insulin levels both at a healthy baseline and after, e.g., induction of a disease state or in response to cognitive challenge, is essential to advance our understanding of both insulin's procognitive actions and to guide potential therapeutic interventions.

We first sought to establish a sampling technique for insulin within awake and moving rats …

The Multifaceted Role Of Glutamate At Excitatory And Inhibitory Synapses, Maurice A. Petroccione

Electronic Theses & Dissertations (2024 - present)

Our thoughts, memories, and actions are finely controlled by the coordinated activity of neural circuits in the brain. Prior work has identified a multitude of molecular mechanisms that contribute to the generation of these higher order functions, yet we know very little about how our ability to learn and perform habitual actions change depending on how far neurotransmitters released from neurons can travel away from their point of release. This is the main focus of my work, which I carried out using a diverse toolbox and focusing on two brain regions: the hippocampus and the striatum. The hippocampus controls learning …

Characterization Of Corticotropin Releasing Factor Receptor 2 In Stress-Regulating Regions Of The Mouse Brain, Jennifer J. Lafrican

Electronic Theses & Dissertations (2024 - present)

Sex differences in the morphology of the brain are thought to underlie the sex differences we see in anxiety and depression, where women are twice as likely to be diagnosed when compared to men. Stress, or a disruption to homeostasis, can exacerbate these mood disorders. Corticotropin releasing factor (CRF), and its receptors, play an important role in regulating the stress response. Binding of CRF with CRFR2 has been shown to reduce behavioral and neuroendocrine stress responses, yet whether there are sex differences in CRFR2 expressing neurons and stress-induced activation of these neurons in mice is unknown, in part due to …

Investigating The Human Face Processing Network: Insights From Acquired Prosopagnosia And Hyperfamiliarity For Faces, Marie-Luise Kieseler

Dartmouth College Ph.D Dissertations

Human faces provide essential social cues that we interpret rapidly, allowing us to recognize identities, interpret emotions, and gauge familiarity. This thesis explores face processing disruptions in four case studies, each offering new insights into the brain’s face recognition mechanisms.

Chapter one presents Annie, a 28-year-old woman who acquired prosopagnosia (face blindness) following COVID-19. After recovering from the severe symptoms of the infection, Annie experienced significant difficulty in recognizing familiar faces and navigating familiar environments. Testing confirmed her impairment in face recognition but showed her preserved cognitive and basic visual processing abilities. Annie was still able to recognize objects and …

Determination Of Electrochemical Parameters For Predicting Reaction Mechanism And Algorithmic Approaches To Pain Assessment, Huize Xue

Dissertations

This dissertation introduces novel advancements in electrochemical kinetics and pain assessment, structured into two main parts. The first part focuses on the comprehensive analysis of the kinetic and mechanistic aspects of electrochemical reactions, utilizing a combination of experimental techniques and simulation methods. A new software tool, Envismetrics, was developed using Python to facilitate the analysis of complex electrochemical data, including cyclic voltammetry (CV), chronoamperometry (CA), and hydrodynamic voltammetry (HDV). The software was rigorously tested and validated with well-characterized redox systems such as the ferricyanide/ferrocyanide couple, dimethylamine borane (DMAB), and Per- and Polyfluoroalkyl Substances (PFAS). It was successfully used to determine …

Can Animal Consciousness Be Resolved Scientifically?, Yoram Gutfreund

Animal Sentience

Carolyn Ristau's biography of Donald Griffin is a comprehensive work that sheds light on a seminal chapter in the history of ethology—the ambitious attempt to establish a research field dedicated to animal consciousness. Although Donald Griffin's endeavor ultimately fell short of its revolutionary goals, it catalyzed significant progress in understanding evolution and mechanisms of animal cognition.

Regulation And Function Of Mec-2 Alternative Splicing In Single Cells, Canyon Calovich-Benne

Biological Sciences Theses and Dissertations

One mechanism for generating diversity at the single cell level is selective expression of a unique set of transcription factors (TFs) and RNA binding proteins (RBPs). These regulatory factors contribute to functions of cells by controlling cell fate, turning genes on and off, and processing of transcripts either co- or post-transcriptionally. Many genes, especially neuronal genes, have multiple different splicing events, promoters, and/or polyadenylation sites. Post-transcriptional coordination is in the infancy of being studied and the functional consequences of this coupling at the single cell level has yet to be explored. Here we show, mec-2 coordination of alternative transcription start …

Novel Digital Anomalies, Hippocampal Atrophy, And Mutations Expand The Genotypic And Phenotypic Spectra Of Cnksr2 In The Houge Type Of X-Linked Syndromic Intellectual Development Disorder (Mrxshg), Mohammad Reza Ghasemi, Sahand Tehrani Fateh, Afif Ben-Mahmoud, Vijay Gupta, Lara G. Stühn, Gaetan Lesca, Nicolas Chatron, Konrad Platzer, Patrick Edery, Hossein Sadeghi, Bertrand Isidor, Benjamin Cogné, Heidi L. Schulz, Ilona Krauspe-Stübecke, Radhakrishnan Periyasamy, Sheela Nampoothiri, Reza Mirfakhraie, Sahar Alijanpour, Steffen Syrbe, Ulrich Pfeifer, Stephanie Spranger, Kathrin Grundmann-Hauser, Tobias B. Haack, Maria T. Papadopoulou, Tayrine Da Silva Gonçalves, Eleni Panagiotakaki, Alexis Arzimanoglou, Seyed Hassan Tonekaboni, Yves Lacassie, Et Al

School of Medicine Faculty Publications

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12. CNKSR2, also known as CNK2 or MAGUIN, functions as a synaptic scaffolding molecule within the neuronal postsynaptic density (PSD) of the central nervous system. It acts as a link connecting postsynaptic structural proteins, such as PSD95 and S-SCAM, by employing multiple functional domains crucial for synaptic signaling and protein–protein interactions. Predominantly expressed in dendrites, …

How Do Anxiety, Stress, Impulsiveness, And Sleep Quality Affect Memory, Hodavia Tshiya Kaseya

Online Theses and Dissertations

Memory is a critical cognitive function that enables individuals to retain, recall, and apply knowledge across various contexts. Different memory systems, including working memory and long-term memory, collaborate to process and store information. Factors such as stress, sleep disturbances, anxiety, and impulsiveness can impact memory encoding and retrieval, especially in college students, whose academic success depends heavily on memory performance. This study examined the relationship between these everyday factors and memory performance by analyzing brain activity during memory encoding using Electroencephalography (EEG) and the Difference due to memory (DM) event-related potential (ERP) effect, to understand how stress, sleep, anxiety, and …

Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia

Honors Scholar Theses

Ependymomas (EPNs) are primary brain tumors that often arise from radial glial cells lining the ventricular system. Supratentorial ependymomas (ST-EPNs) are particularly aggressive, and understanding the molecular factors driving their growth is critical for developing targeted therapies. This study investigates the roles of DLK1 and EGR1, key regulators in cellular differentiation and tumorigenesis, in the development of ST-EPNs. We utilized genetically engineered mouse models to induce postnatal knockouts of DLK1 and EGR1 and evaluated tumor growth using histological and imaging techniques. Tumor area was quantified across multiple brain sections from both male and female mice. DLK1 knockout brains exhibited consistent …

Conceptual Curiosity: Sense(Un)Making, Rebekah L. Cowell

Proceedings from the Document Academy

Across disciplines, sensemaking is a theoretical and methodological research program, over forty years in development, that has been treated as a framework for understanding how humans behaviorally respond to external information sources and interpret to construct and actualize actionable outcomes; however, sensemaking is an interlinking process that does not operate in singularity–behaviorally or actionably–it is neurobiological (autonomous drive), cognitive (perceptual and predictive), and psychological (congruency in meaning).

This paper enlarges the conceptual framework for studying sensemaking and redefines it by addressing what sensemaking is, does, and needs. At the core of this conversation is addressing the absence of knowledge and …

Are There Neurological Impacts Of Exposure To A Burned Wildfire Site As It Recovers?, Rubye Strickland

Undergraduate Honors Theses

Wildfires are increasing with climate change, making the human health implications of exposure to burned soils an essential area of research. Metals associated with fire-impacted soils can be inhaled or accidentally ingested by surrounding communities, causing health risks. Several studies have evaluated the health impact of wildfires, but few have done so from a neurological perspective. This study explores metal changes in burned soils over time as a site naturally recovers from wildfire and how these changes may impact human neurological health. Soil samples were collected from the burned area 0, 3, 6, 9, and 12 months after the fire. …

Sk609, A Novel Dopamine D3 Receptor Agonist And Norepinephrine Transporter Blocker With Putative Pro-Cognitive Actions, Does Not Induce Psychostimulant-Like Increases In Risky Choice During Probabilistic Discounting, Christopher P. Knapp, Brooke Fallon, Sandhya Kortagere, Barry D. Waterhouse, Stan B Floresco, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

RATIONALE: Psychostimulants, such as amphetamine (AMPH) and methylphenidate (MPH), non-selectively elevate extracellular concentrations of the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), and are common pharmacological strategies used to improve prefrontal cortex (PFC)-dependent cognitive dysfunction. However, this approach can be problematic given AMPH has been shown to increase preference for risky choices in a rodent assay of risk/reward decision making. SK609 is a novel NE reuptake blocker that selectively activates DA D3 receptors without affinity for the DA transporter. SK609 has been shown to improve cognitive performance without increasing psychostimulant-like spontaneous locomotor activity, suggesting SK609 may benefit neurocognitive function without …

Sympathetic Innervation Of Interscapular Brown Adipose Tissue Is Not A Predominant Mediator Of Ot-Elicited Reductions Of Body Weight Gain And Adiposity In Male Diet-Induced Obese Rats, Melise Edwards, Ha Nguyen, Andrew Dodson, Adam Herbertson, Mackenzie Honeycutt, Jared Slattery, June Rambousek, Edison Tsui, Tami Wolden-Hansen, Tomasz Wietecha, James Graham, Geronimo Tapia, Carl Sikkema, Kevin O'Brien, Thomas Mundinger, Elaine Peskind, Vitaly Ryu, Peter Havel, Arshad Khan, Gerald Taborsky, James Blevins

Selected Works Temporary Series

Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (TIBAT) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats. To test this, we determined the effect of disrupting SNS activation of IBAT on …

Sympathetic Innervation Of Interscapular Brown Adipose Tissue Is Not A Predominant Mediator Of Ot-Elicited Reductions Of Body Weight Gain And Adiposity In Male Diet-Induced Obese Rats, Edwards, Ha Nguyen, Andrew Dodson, Adam Herbertson, Mackenzie Honeycutt, Jared Slattery, June Rambousek, Edison Tsui, Tami Wolden-Hansen, Tomasz Wietecha, James Graham, Geronimo Tapia, Carl Sikkema, Kevin O'Brien, Thomas Mundinger, Elaine Peskind, Vitaly Ryu, Peter Havel, Arshad Khan, Gerald Taborsky, James Blevins

Departmental Papers (Biology)

Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that  administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (TIBAT) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats. To test this, we determined the effect of disrupting SNS activation of IBAT on …

Neuroplasticity And Creativity: Transformative Potential Of Fibre Arts For Growth And Well-Being, Piper Hutson, James Hutson

Faculty Scholarship

This article explores the transformative potential of fibre arts—such as quilting, weaving, and embroidery—as tools for personal growth, neuroplasticity, and well-being. Drawing on neuroscience and psychology, it demonstrates how engaging with fibre arts stimulates brain regions associated with problem-solving, sensory integration, and adaptability, fostering neural growth and enhancing cognitive flexibility. Fibre arts, through their inherent challenges and opportunities for play, provide a perfect medium for stepping beyond familiar boundaries, cultivating resilience, and reducing stress. This interplay of creativity and tactile engagement is particularly effective due to the historical undervaluation of fibre arts, which makes them novel and accessible mediums that …

Beyond Pathology: Inclusive Mentorship, Accommodations, And Policy Reforms For Autistic Women In The Medical Profession, Piper Hutson, James Hutson

Faculty Scholarship

This article addresses the unique challenges faced by autistic women in the medical profession, particularly in navigating traditional medical frameworks that often marginalize neurodiverse individuals. Drawing from a targeted literature review, this paper highlights the importance of adapting medical curricula, establishing mentorship programs, and reforming policies to foster inclusivity. Autistic women in medicine encounter barriers such as a lack of mentorship tailored to their needs, inadequate accommodations, and systemic bias rooted in the pathologization of autism. The article synthesizes current research to provide evidence-based recommendations that address these barriers. Specific examples of successful mentorship programs demonstrate the critical role of …

Expanding Sensory Kit Utilization Across Age And Contexts: Bridging Gaps For Inclusive Accessibility, Piper Hutson, James Hutson

Faculty Scholarship

Sensory kits, initially developed for neurodivergent children, have seen growing integration into various educational, cultural, and therapeutic contexts. However, their broader applicability, particularly for adults and diverse populations, remains underexplored. This study examines existing practices in the design and use of sensory kits within academic, museum, and inclusion frameworks, highlighting their role in promoting focus, reducing anxiety, and supporting self-regulation. Using case studies from institutions such as the Smithsonian and the Metropolitan Museum of Art, alongside a review of evidence-based interventions like weighted items and fidget tools, the research underscores the potential of these tools in diverse environments. The methodology …

Unilateral Tongue Atrophy In Smad3: A Case Report, Gloria Galloway

Nursing & Health Sciences Research Journal

Background: Mothers Against Decapentaplegic Homolog 3 (SMAD3) is a disorder of the protein encoded at locus 15q22.33 and involved in the transcription of growth factor-beta (TGF) signalling. In this disorder, SMAD3 encoding is impaired, resulting in a connective tissue disorder with multisystem involvement (Bertoli-Avella et al., 2015; Dulac et al., 2019). This case is the first to describe unilateral tongue atrophy as an initial presentation of SMAD3, thereby providing an important contribution to the literature. Clinical History and Exam: A 43-year-old patient described a 1–2-week history in which he noted that half of his tongue had wasted away, and he …

Neurological Foundations And Technological Interventions For Dyslexia: Advancements And Challenges, Piper Hutson, James Hutson

Faculty Scholarship

Dyslexia, a complex neurological condition affecting reading and language processing, is intricately tied to variations in brain structure and function. This article explores the neurological underpinnings of dyslexia, emphasizing phonological, visual, and attention-related impairments. Furthermore, the analysis highlights various types of dyslexia—phonological, surface, rapid automatized naming, and visual—while addressing their neurological correlations. It also investigates the relationship between dyslexia and other neurodivergent conditions, such as autism and ADHD, focusing on the neurological overlap and differences. To mitigate the challenges associated with dyslexia, advanced technologies such as Virtual Reality (VR) and eye-tracking are discussed for their diagnostic and intervention potential. These …

Investigating Brain Reward Mechanisms: A Comparative Study In Male And Female Rats, Valeria Garcia

Open Access Theses & Dissertations

Drug addiction is a serious public health concern. Recently, electronic cigarette use has become increasingly popular among vulnerable populations such as adolescents and women. Previous research on conventional cigarette use has shown significant sex differences in drug-seeking behavior and withdrawal symptoms, which are driven mainly by hormonal differences. However, changes in sex hormones do not completely explain the enhanced reward sensitivity reported in females. Thus, this dissertation aims to examine other alternative reasons that can explain these sex differences, such as differences in reward-seeking and neuronal reactivity. Additionally, there is a dearth of consistency across papers intending to map electrode …