Mental Health Research, Social Issues / 26.12.2023

In the fast-paced, interconnected world we now live in, the prevalence of burnout has become a concerning reality for many. The term was first coined in the 1970s to describe the chronic workplace stress that led to physical and emotional exhaustion. Since then, if you are feeling run down and exhausted you may well be yet another victim of modern-day fatigue. Here is a look at the nuances of burnout and some key factors contributing to this pervasive problem. Burnout goes beyond the workplace While burnout traditionally has its roots in a professional workplace setting, modern-day pressures means that the phenomenon now extends beyond the confines of the workplace. Burnout now encompasses a holistic exhaustion that permeates various aspects of life. These include personal relationships, social interactions, and even leisure activities. We have even reached a point where The World Health Organization (WHO) officially recognized burnout as a syndrome in the International Classification of Diseases, emphasizing its impact on overall well-being. (more…)
Author Interviews, Environmental Risks, JAMA, McGill, Mental Health Research / 06.11.2023

MedicalResearch.com Interview with: Niki Hosseini-Kamkar PhD Postdoc, McGill University MedicalResearch.com: What is the background for this study? Response: Our primary question was: Do adults with a history of childhood trauma have altered brain responses to psychological challenges? Previous evidence indicated that this can occur in laboratory animals, but it has been unclear whether it occurs in humans. (more…)
Author Interviews, Mental Health Research, Microbiome, Nature, OBGYNE, UCLA / 25.07.2023

MedicalResearch.com Interview with: Bridget Callaghan Ph.D. Assistant Professor of Psychology UCLA Dr. Callahan studies interactions between mental and physical health across development.   MedicalResearch.com: What is the background for this study? Response: A growing body of evidence links the gut microbiome to brain and immune functioning, and changes to that community of microorganisms is likely among the ways that hardship affects children’s socioemotional development. Limited evidence in humans has demonstrated the adversities experienced prenatally and during early life influence the composition of the gut microbiome, but no studies had examined whether stress experienced in a mother's own childhood could influence the microbiome of the next generation of children. (more…)
Author Interviews, Mental Health Research, Stroke / 06.12.2021

MedicalResearch.com Interview with: Professor Andrew Smyth MB, BCh, BAO, MMedSc, MRCPI, PhD Professor of Clinical Epidemiology NUI Galway Director of the HRB-Clinical Research Facility Galway Consultant Nephrologist at Galway University Hospitals MedicalResearch.com: What is the background for this study? Response: We know that there are multiple medium to long-term risk factors for stroke, as people with conditions such as hypertension (high blood pressure) or diabetes mellitus (high blood glucose levels) and those with risk factors (such as smoking, obesity, poor diet quality and others) are at increased risk of stroke. However, we still find it difficult to predict who will have a stroke. We were interested in exploring if short-term exposures to anger or emotional upset or a period of heavy physical exertion might lead to, or ‘trigger’ a stroke. We looked at this previously for myocardial infarction (heart attack) in a study called INTERHEART. Some smaller studies have looked at this before, with less people experiencing a stroke and often confined to one country or geographical region. Here, in INTERSTROKE, we included over 13,000 people who had a stroke and asked about the one hour period before the onset of the stroke and also about the same period on the day before.  (more…)
Author Interviews, Neurological Disorders, Neurology, Pain Research / 11.05.2020

MedicalResearch.com Interview with: Holly Yancy, DO Headache medicine specialist Banner – University Medicine Neuroscience Institute Phoenix, AZ Dr. Yancy comments on the recent Neurology journal article on the potential impact of yoga on migraine.  MedicalResearch.com: What is the background for this study? How might yoga reduce migraine intensity or frequency?  Response: The authors of this trial have studied the benefits of yoga when added to medical management of episodic migraine. They expand on prior, smaller reports of the potential benefit of yoga and mindfulness to migraine patients with a well-designed study that shows yoga, as an adjunct to preventive medication, can lower the intensity, frequency and impact of migraines. Participants even used less abortive medication. The authors propose multiple potential mechanisms of action, including an increase in parasympathetic / decrease in sympathetic nervous system activity, decreased muscle tension, and stress management. (more…)
Author Interviews, Emory, Heart Disease / 13.09.2019

MedicalResearch.com Interview with: Viola Vaccarino, MD, PhD Wilton Looney Professor and Chair in Cardiovascular Research Dept. of Epidemiology, Rollins School of Public Health Professor, Dept. of Medicine, School of Medicine Emory University MedicalResearch.com: What is the background for this study? Response: Psychological stress has been linked to increased risk for cardiovascular disease. The mechanisms have not been clear. One hypothesis has been that chronic or repeated exposure to psychological stress can cause a phenomenon of “wear-and-tear” of the vascular system due to activation of the neuroendocrine stress systems, eventually leading to accelerated plaque formation and adverse cardiovascular events. However, this has never been demonstrated in humans. In some individuals, psychological stress can induce a transitory impairment of the endothelium, a phenomenon known as endothelial dysfunction. A healthy endothelium is essential in blood flow regulation and in maintaining cardiovascular health. (more…)
Author Interviews / 20.08.2019

MedicalResearch.com Interview with: William R. Lovallo, Ph.D. Reseacher, University of Oklahoma College of Medicine MedicalResearch.com: What is the background for this study? Response: We have been interested for some time in why some people are at high risk for alcoholism.  Most work in the field of addictions is focused on persons who are already impacted by their exposure to alcohol or drugs.  We wanted to know what they were like before that phase of their  lives.  So, in 1999 we began the Family Health Patterns Project to study healthy young adults 18-30 years of age with and without family histories of alcoholism but who were not alcoholics themselves.  A family history is the best known, and perhaps strongest, risk factor for future drinking problems. We asked ourselves are the two family-history groups different?  And if so, how are they different?  There was at that time little literature to build on so we decided to look at as many things as we could.  We began recruiting volunteers for our family-history positive and negative groups and evaluating them with a standard psychiatric interview, personality tests, measures of depressive mood and neuroticism, and measuring physiological reactivity to stress.  In doing so we also began collecting DNA and studying basic genetic variants to see if any of those might be revealing. (more…)
Author Interviews, Environmental Risks / 26.07.2019

MedicalResearch.com Interview with: Patricia Pendry Ph.D. Associate Professor of Human Development Graduate Faculty in Prevention Science Washington State University CAHNRS Pullman, WA 99164  MedicalResearch.com: What is the background for this study? Response: Over the last decade, university students have reported increasingly high levels of academic stress, depressive symptomology, anxiety, and suicidal ideation. This is a serious problem as students who report these symptoms tend to have lower GPAs and are more likely to drop out of college. Since academic stress is considered an inevitable part of college life, it is important that we identify effective academic stress management programs. One stress management approach that has been enthusiastically received by University administrators and students is the use of campus-based Animal Visitation Programs (AVPs). Established in nearly 1,000 U.S. college campuses to date, most AVPs provide the general student population the opportunity to engage in 5-30 minutes of petting of animals in small-group settings. While students much enjoy these types of programs, relatively little sound scientific evidence is known about the efficacy of such programs to actually reduce stress. We thus embarked on a study that experimentally teased out the effects of hands-on interaction from the effects of waiting in line while watching others engage in hands-on interactions, sitting quietly without social media or other stimuli, or watching pictures of the same animals on students’ level of salivary cortisol, a stress hormone that has been linked to various physical and mental health outcomes. (more…)
Author Interviews, JAMA, Mental Health Research, Surgical Research, UCSF / 27.05.2019

MedicalResearch.com Interview with: Carter Lebares, MD Assistant Professor of Surgery Director, Center for Mindfulness in Surgery Department of Surgery, UCSF  MedicalResearch.com: What is the background for this study?  Response: This study was inspired by extensive evidence of the effectiveness of mindfulness-based interventions (MBIs) for mitigating stress and enhancing performance in other high-stress populations like police and the military.  We know that overwhelming stress is related to burnout and to cognitive errors - two critical issues within surgery, today. This prompted us to tailor and streamline an MBI specifically for surgeons, and to test it in our trainees. (more…)
Author Interviews, Mental Health Research / 26.04.2019

MedicalResearch.com Interview with: Yoshinori SUGIURA Ph.D. Associate Professor Hiroshima University Graduate School of Integrated Arts and Sciences Behavioural Sciences Section Higashi-Hiroshima, Japan  MedicalResearch.com: What is the background for this study? Response: Lengthy worrying or repeated checking if the door is locked are common manifestations of anxiety in the general population. However, if their frequency, intensity, and interference become too much, they are diagnosed as Generalized Anxiety Disorder (GAD) and Obsessive Compulsive Disorder (OCD) respectively. People with OCD are tortured by repeatedly occurring negative thinking and they take some strategy to prevent i. GAD is a very pervasive type of anxiety. GAD patients worry about everything. Despite their burden, both are relatively difficult to treat. Furthermore complicated, as they are two different disorders, mental health professionals have to master separate strategies. To overcome such situation, transdiagnostic research, which seeks common causes for different disorders, is now eagerly pursued by psychologists/psychiatrists. As one of such endeavors, we predicted that inflated responsibility is the common predictor of both OCD and GAD symptoms. (more…)
Author Interviews, BMJ, Heart Disease, Karolinski Institute / 11.04.2019

MedicalResearch.com Interview with: Huan Song, PhD Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden MedicalResearch.com: What is the background for this study?   Response: Cardiovascular disease (CVD) presents a group of diseases that are common and sometimes fatal in general population. The possible role of stress-related disorders in the development of CVD has been reported. However, the main body of the preceding evidence was derived from male samples (veterans or active-duty military personnel) focusing mainly on posttraumatic stress disorder (PTSD) or self-reported PTSD symptoms. Data on the role of stress-related disorders in CVD in women were, until now, limited. Although incomplete control for familial factors and co-occurring psychiatric disorder, as well as the sample size restriction, limit the solid inference on this association, especially for subtypes of CVD. (more…)
Accidents & Violence, Author Interviews, JAMA, Social Issues / 06.01.2019

MedicalResearch.com Interview with: Rebecca R. Thompson, Ph.D. Postdoctoral Scholar Department of Psychological Science University of California, Irvine MedicalResearch.com: What is the background for this study? Response: Our research team has been interested in how people respond to the repeated threat of disaster exposure for many years. We recently published a review of the literature on evacuation from natural disasters, and one of our main findings was that there have been no studies that include assessments of individuals’ intentions, perceptions, and psychological states assessed prior to an approaching storm’s landfall – all prior research has been retrospective, and recall is undoubtedly biased and unreliable.  Our goal in undertaking this study was to fill this hole in the literature. We sought to assess individuals' responses to Hurricane Irma in the days leading up to and immediately after its landfall in the State of Florida. (more…)
Author Interviews, Environmental Risks, Heart Disease, Nutrition / 05.12.2018

MedicalResearch.com Interview with: Dr. Lowell H. Steen, Jr., M.D. Interventional Cardiologist Loyola University Medical Center Dr. Steen discusses how holiday treats & stress can increase the risk of heart attack. MedicalResearch.com: What are the main factors that are linked to an increase in heart related adverse events during the Christmas holiday season? Who is most at risk?  Response: The increase in holiday season heart-related hospitalizations and deaths are due to a variety of behaviors such as putting off seeking medical help until after the holidays, overeating rich foods, strenuous travel, excessive alcohol consumption and stressful family interactions. These factors can all trigger heart issues. Factors such as age, diabetes, high cholesterol and smoking all increase heart risk. Additionally, those with high blood pressure, which is a leading risk factor for heart disease and stroke, are exceptionally at risk and should celebrate the hectic holiday season with caution.  (more…)
Author Interviews, Circadian Rhythm / 28.11.2018

MedicalResearch.com Interview with: Yujiro Yamanaka, Ph.D. Associate Professor Hokkaido University Graduate School of Education Sapporo, Japan  MedicalResearch.com: What is the background for this study? Response: My laboratory has focused on the human circadian rhythms in particularly investigating the time of day effect of non-photic cues especially physical exercise and psychological stressor on circadian rhythms. In mammals including humans, the central circadian pacemaker is located in the suprachiasmatic nucleus (SCN) in the brain hypothalamus. The SCN entrains to an external light-dark cycle and generates endogenous 24 h rhythmicity in body function. The hypothalamic-pituitary-adrenal (HPA) axis is our major stress response system. We can assess the response of HPA axis to psychological stress event by measuring the level of glucocorticoid hormone, cortisol in saliva. The cortisol shows clear circadian rhythm with higher levels in the morning and lower levels in the evening. This rhythm is generated by the SCN circadian pacemaker. Previous study (Kudielka et al. Psychoneuroendocrinology 2004) could demonstrate that the cortisol stress level is significantly elevated by acute psychological stress event in the morning (9 a.m. to 10 a.m.) and afternoon (3 p.m. to 4 p.m.). However, there are no study examining the effect of evening psychological stress event on the HPA axis activity. Thus, our new study focused on examining whether the HPA axis differentially responses to morning and evening stress event in healthy subjects. (more…)
Author Interviews, Genetic Research, Pediatrics / 28.09.2018

MedicalResearch.com Interview with: Barry M. Lester, PhD Center for the Study of Children at Risk Warren Alpert Medical School, Brown University Women and Infants Hospital of Rhode Island Providence, Rhode Island;  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We know from rodent studies that maternal care or nurturing behavior can change the rat pups physiologic response to stress. More nurturing behavior makes it easier for rat pups to relax after stress. Not only that, these changes are permanent, they last into adulthood and there is evidence that these changes can be passed on to the next generation. With animal studies you can unlock the mechanism for this in ways that you can’t do with humans and we know from the rodent studies that the mechanism for these changes has to do with changes in gene activity. Nurturing behavior controls a specific gene that regulates the infant’s physiological response to stress. In other words, we are looking at maternal behavioral programming of a gene that can make, in our case, a human infant less physiologically reactive to stress. The physiological reactivity to stress that we studied was the production of the stress hormone cortisol. Cortisol is part of the body’s flight or fight reaction, the body’s major response to stress and too much or too little cortisol can be harmful and is related to a wide range of mental and physical health disorders in children and adults. The concerns about separating immigrant children from their parents that we read about every day in the paper are based on this same physiological system, where brain structures that control cortisol production are damaged by the stress of separation.  (more…)
Author Interviews, Endocrinology, Pediatrics, Race/Ethnic Diversity / 23.09.2018

MedicalResearch.com Interview with: Julie Flom, MD MPH Clinical Fellow Division of Allergy & Immunology Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study?   Response: Women who are minorities and of lower socioeconomic have particularly high rates of exposure to chronic ongoing adversity such as poverty as well as traumatic stressors in their lifetime and are also more likely to have low birthweight infants.  Not all women exposed to chronic adversity or trauma transfer this risk to the next generation – it is primarily when the trauma results in changes in her bodies’ ability to handle ongoing stress that the developing child can be impacted. Our group undertook a study to investigate whether women with increased exposure to traumatic stressors over her lifetime were at higher risk of having low birthweight infants and also whether effects of trauma would only be evident among women who produced higher levels of cortisol, the major stress response hormone, while pregnant. (more…)
Author Interviews, JAMA, Karolinski Institute, Mental Health Research, PTSD, Rheumatology / 21.06.2018

MedicalResearch.com Interview with: Huan Song Associated Department of Medical Epidemiology and Biostatistics Karolinska Institutet MedicalResearch.com: What is the background for this study? Response: Earlier findings from our group (e.g. Fang et al., NEJM 2012; Arnberg et al., Lancet Psychiatry 2015; Lu et al., JAMA Oncol 2016; Shen et al., BMJ 2016; Zhu et al., Ann Oncol 2017) have identified pathways through which stressful events contribute to deterioration in human health. With strong animal models and human data supporting a role of stress in immune dysregulation, the hypothesis linking mental distress with autoimmune is indeed plausible. However, the evidence is as yet limited to clinical observations and a few larger observational studies on US veterans, most of them on men only, and some of which have cross-sectional designs and various other methodological shortcomings. (more…)
Author Interviews, Mental Health Research, Pediatrics / 02.05.2018

MedicalResearch.com Interview with: “dog” by Neil Mullins is licensed under CC BY 2.0Prof. Dr. rer. nat. Stefan O. Reber Laboratory for Molecular Psychosomatics Clinic for Psychosomatic Medicine and Psychotherapy University Clinic Ulm Ulm, Germany  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our hypothesis was that people who grew up in cities with more than 100.000 inhabitants  and without pets will show a more pronounced immune activation towards psychosocial stressors compared with people raised in rural areas in the presence of farm animals. This hypothesis is based on the fact that stress-associated psychiatric disorders, which are linked to or even promoted by an over(re)active immune system and chronic low grade inflammation,  are more prevalent in urban compared with rural areas. One possible explanation for a hyper(re)active immune system in people raised in urban relative to rural environments might be a reduced contact to immunoregulatory microorganisms (the so called “old friends”), which is significantly increased in rural people with regular contact with farm animals compared with urban people in the absence of pets. Our results show that a standardized laboratory psychosocial stressor causes a greater inflammatory response in young healthy participants with an urban upbringing in the absence of pets, relative to young healthy participants with a rural upbringing in the presence of farm animals. (more…)
Author Interviews, Cannabis, Social Issues / 31.07.2017

MedicalResearch.com Interview with: Carrie Cuttler, Ph.D. Clinical Assistant Professor Washington State University Department of Psychology Pullman, WA, 99164-4820 MedicalResearch.com: What is the background for this study? What are the main findings? Response: One of the most common reasons cannabis users report using cannabis is to cope with stress. In support of this, previous research has shown that acute administration of THC or cannabis dampens affective responses and subjective stress ratings. This has made strains of cannabis popular for use for stress and other ailments with some online outlets, like high thc having reviews such as the og kush strain review to perpective users. However, our study is the first to compare the stress response of sober cannabis users to non-users. More specifically, we randomly assigned 42 non-cannabis users and 40 cannabis users (who abstained from using cannabis for at least 12 hours prior to the study) to either a stress or no stress condition. Participants in the stress condition were required to perform multiple trials of placing their hand in ice water and counting backwards from 2043 by 17s. Each time they made an error they were given negative feedback and told to start again. Further, they were being video recorded and their image was displayed in front of them. Participants who were assigned to the no stress condition were simply required to perform multiple trials of placing their hand in lukewarm water and counting from 1 to 25. They were not given feedback or recorded. Participants were asked to rate their level of stress and to provide a saliva sample, from which the stress hormone cortisol was measured. The results showed that, as expected, non-users in the stress condition had higher cortisol levels and higher self-reported stress than non-users in the no stress condition. In contrast, cannabis users in the stress condition demonstrated the same levels of cortisol as cannabis users in the no stress condition and their increase in self-reported stress was smaller than that of the non-users. (more…)
Author Interviews, OBGYNE, Pediatrics / 21.07.2017

MedicalResearch.com Interview with: Parvati Singh B. Tech, MBA, MPA PhD student, Department of Public Health, University of California, Irvine and Dr. Tim Bruckner, first author MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study builds upon earlier research by our group which showed that male fetal deaths rose and the number of liveborn males fell after the 9/11 attacks. Here we show that, in California, the number of live born males with birth defects fell after 9/11. This finding appears consistent with the notion that frail male gestations, such as those with defects, may have been lost in utero as a result of the stress induced by the 9/11 attacks. (more…)
Author Interviews, Mental Health Research, Occupational Health, Social Issues / 07.05.2017

MedicalResearch.com Interview with: Tarani Chandola Professor of Medical Sociology Social Statistics Disciplinary Area of the School of Social Sciences University of Manchester MedicalResearch.com: What is the background for this study? Response: We (the authors) were particularly interested in examining evidence for the common perception that people at the top of the occupational hierarchy are the most stressed. And also what happens to people’s stress levels when they retire. We had assumed that people with poorer quality work to have decreased levels of stress when they retired. There have been other studies on this topic before, but none that have used salivary cortisol to measure physiological stress responses. We analysed changes in people’s stress levels before and after retirement, in a follow up study of over 1,000 older workers in the British civil service. Stress levels were measured by taking salivary cortisol samples across the day, from awakening until bedtime. (more…)
Author Interviews, Heart Disease / 15.03.2017

MedicalResearch.com Interview with: Simon Graff MD Department of Public Health Research Unit for General Practice Aarhus University Aarhus C, Denmark  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The presented study is a continuation of our interest in the role of stress and the possible causes of atrial fibrillation.  We published a study that showed that spousal bereavement were followed by a transiently increased risk of new onset of atrial fibrillation. With spousal bereavement being one of the most stressful life-event, we wanted to know whether minor and differentiated stress exposures had an effect as well. Therefore we used register based data on perceived stress as a new measure of exposure. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, Lancet, Medical Imaging, MRI, Social Issues / 12.01.2017

MedicalResearch.com Interview with: Dr Ahmed Tawakol MD Co-Director, Cardiac MR PET CT Program Massachusetts General Hospital and Harvard Medical School  MedicalResearch.com: What is the background for this study? What are the main findings? Response: While the link between stress and heart disease has long been established, the mechanism mediating that risk hasn’t been clearly understood. Animal studies showed that stress activates bone marrow to produce white blood cells, leading to arterial inflammation.  This study suggests an analogous path exists in humans. Moreover, this study identifies, for the first time in animal models or humans, the region of the brain (the amygdala) that links stress to the risk of heart attack and stroke. The paper reports on two complementary studies. The first analyzed imaging and medical records data from almost 300 individuals who had PET/CT brain imaging, primarily for cancer screening, using a radiopharmaceutical called FDG that both measures the activity of areas within the brain and reflects inflammation within arteries.  All participants in that study had no active cancer or cardiovascular disease at the time of imaging and each had information in their medical records on at least three additional clinical visits after imaging. The second study enrolled 13 individuals with a history of post-traumatic stress disorder, who were evaluated for their current levels of perceived stress and received FDG-PET scanning to measure both amygdala activity and arterial inflammation. (more…)
Author Interviews, Autism, Gastrointestinal Disease, Psychological Science / 05.01.2017

MedicalResearch.com Interview with: David Q. Beversdor MD Center for Translational Neuroscience University Hospital University of Missouri Health System Columbia, MO 65212 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Altered stress reactivity, alterations in cytokines and a high incidence of gastrointestinal disturbances have all been observed in autism spectrum disorder (ASD). We wished to examine the interactions between these factors. What we found was that patients with greater stress reactivity, as indicated by cortisol response in the testing environment, had greater symptomatology involving the lower gastrointestinal tract, which was predominated by constipation. (more…)
Author Interviews, Gastrointestinal Disease, Mental Health Research, Nature, Probiotics / 02.12.2016

MedicalResearch.com Interview with: Elizabeth Bryda, PhD Professor, Director, Rat Resource and Research Center Veterinary Pathobiology University of Missouri Columbia, Missouri MedicalResearch.com: What is the background for this study? What are the main findings? Response: A number of groups have demonstrated the ability of probiotics to benefit digestive health and there is a growing body of evidence to suggest an association between mental health and “gut health”. We were interested to see if probiotic bacteria could decrease anxiety- or stress-related behavior in a controlled setting using zebrafish as our model organism of choice for these studies. We were able to show that Lactobacillus plantarum decreased overall anxiety-related behavior and protected against stress-induced dysbiosis (microbial imbalance). The fact that administration of probiotic bacteria also protected other resident gut bacteria from the dramatic changes seen in “stressed” fish not receiving the probiotic was unexpected and suggested that these bacteria may be working at the level of the GI tract and the central nervous system. (more…)
Accidents & Violence, Author Interviews, JAMA, Pediatrics / 15.11.2016

MedicalResearch.com Interview with: Katherine P. Theall, PhD Associate Professor Global Community Health and Behavioral Services Tulane University School of Public Health and Tropical Medicine New Orleans, Louisiana MedicalResearch.com: What is the background for this study? What are the main findings? Response: There are stark health disparities in the U.S. by socioeconomic position as well as between racial and ethnic groups. Many of these health disparities may have a root cause in childhood and be driven by social risk factors. The authors report each neighborhood stressor was associated with biological stress as measured by shortened telomere length and cortisol functioning. Many children are exposed to violence and a greater understanding of the effect on children’s health is critical because social environmental conditions likely contribute to health disparities. Socioeconomically disadvantaged communities have a higher exposure to violence. Limitations of the study include its lack of applicability to other demographic groups. The study also cannot establish causality. (more…)