Statistical Analysis Of A Class: Monte Carlo And Multiple Imputation Spreadsheet Methods For Estimation And Extrapolation

The Monte Carlo method and related multiple imputation methods are traditionally used in math, physics and science to estimate and analyze data and are now becoming standard tools in analyzing business and financial problems.  However, few sources explain the application of the Monte Carlo method for individuals and business professionals who are not immersed in the realm of mathematics or science.  This paper introduces these Monte Carlo methods for the non-mathematician and business student, providing examples where the Monte Carlo method is applied when only small samples are available.  Statistical analysis and statistically sound extrapolation of sample characteristics to the larger class population can be facilitated by applying Monte Carlo methods and the related concept of multiple imputation, which is also explained.  Appendices provide step-by-step instructions for using two popular spreadsheet add-ins to run Monte Carlo based analysis

Rewiring the stress response: A new paradigm for health care Introduction

Many diseases including obesity, irritable bowel syndrome, gastroesophageal reflux disease, depression, anxiety, chronic pain and headaches are symptoms of stress or exacerbated by stress. Stress occurs when an individual's perception or responses suggest that environmental demands tax or exceed his or her ability to cope (1). Identifying and modifying the brain circuits that trigger maladaptive stress responses should result in overall health improvement and likely decrease reliance on medications, procedures and devices. The hypothalamic-pituitary-adrenocortical axis (HPA) and the sympathetic-medullo-adrenal (SMA) system are activated in response to a stressor or fear. Their prolonged or repeated activation interferes with most physiological systems, resulting in increased risk for physical and psychiatric disorders (2-4). Links between stress and disease have been reported for depression (5-8), obesity (9-10) and cardiovascular disease (11)(12)(13)(14)(15). Each of the top ten causes of death in the United States is caused by or exacerbated by stress (16). Nationally, 75 % of adults report experiencing moderate to high levels of stress in the past month and 42 % report that their stress has increased in the past year (17). As much as 75-90 % of primary care office visits are due to symptoms that have stress related components (18). In 1979, Laurel Mellin began developing a treatment program for obesity In describing the conceptual basis of a stress intervention method, Emotional Brain Training (EBT), a program which integrates advances in neuroscience and stress physiology, we propose a new paradigm for health care. Many health care treatments focus on managing symptoms of stressrelated disorders. In modern society stress is primarily psychological in nature and in its chronic form, the result of allostatic (non-homeostatic) neural circuits that amplify and prolong stress. The result is cognitive, emotional, behavioral and physiologic dysregulation resulting in wear and tear (allostatic load). The effectiveness of treating any one stress symptom is likely decreased because of the persistent allostatic state. Emerging understanding of neuroplasticity suggests that this circuitry is capable of change. EBT is based on the repeated use of techniques that mirror secure attachment and optimal self-regulatory processing to alter allostatic circuits through the process of reconsolidation, therefore decreasing allostatic load. This results in an improved state of well-being. We hypothesize that decreased dominance of allostatic neuronal circuits leads to improved health outcomes, offering a new paradigm for health care. in the areas of neuroplasticity, emotion research, stress biology and attachment theory. The neuroscience of rewiring self-regulation utilized by EBT is based on physiologic brain states of stress. The skills used to rewire the stress response are based on four core concepts enumerated below. Concept 1: It's not us. It's our wiring. The full-blown stress response evolved in reaction to an imminent threat to survival -it is triggered rapidly and nonspecifically (22). However, this kind of threat is rare in modern society leading to an often inappropriate triggering of the full-blown stress response. The wiring that triggers this unnecessary, amplified or prolonged stress response is stored in the unconscious implicit memory systems (23) via the HPA and SMA axes (24). The self-regulatory processing is learned from parental interaction with his/her infant. In combination with genetic and environmental factors, the attachment between parent and child is encoded in the circuits of the infant's brain. This attachment is the result of the capacity of the parent to appraise the emotional state of the offspring and take necessary actions to change the child's physiology from stress to well-being, optimizing the chances for survival. Those early connections, especially before the age of three, or later in life during periods of trauma, form the basis for the circuitry of resiliency and health (25-28). These circuits may be effective or ineffective. Each new stress stimulus is compared with internal representations of past experiences stored in our memory. These representations are "archived" in neural circuits whose activation enables the brain to bring elements of past experience forward in time and to anticipate future stressors in order to respond effectively to the current milieu We hypothesize that the self-regulatory circuitry that responds to stress and reflects potentiation involves three phases: 1) quick sub-cortical processing phase (responses of the HPA and SMA axes), which is nonspecific, evolutionarily based and primarily emotive (based in fear) (34); 2) cortical/cognitive processing of emotions into conscious feelings based on expectations and past experiences -the second phase concludes with the identification of needs; 3) generation of thoughts and actions to marshal a corrective response to meet those perceived needs. The process, if adaptive, returns the person to a state of well-being. Each episode of stress may arouse self-regulatory circuitry that is an effective (adaptive) or ineffective (maladaptive) response to the stressor. The effective response or homeostatic circuit is a self-correcting, negative feedback loop, leading to a state of well-being. It triggers an emotional response that is consistent with the actual stressor, a cortical processing phase that is effective in discerning the true need based on reasonable expectations, and finally, a corrective action that returns the organism to a state of well-being, quickly and easily. Ultimately, physical, emotional, psychological and behavioral homeostasis is restored. The ineffective response (activation of an allostatic circuit) is a positive feedback loop and not self-correcting. It arouses an emotional processing that underor over-reacts to the actual stressor, a cortical processing phase that is based on unreasonable expectations and, thus, ineffective in identifying the actual need, and finally, a corrective action that does not return the person to a state of well-being. Ultimately, this prolongs and amplifies the stress response and becomes the source of stress in its own right (35). It all depends on the active wiring. Concept 2: Wiring triggers brain states. To promote the survival of the species, the brain has evolved into an organized hierarchy, which includes the simple, quick, regulatory functioning of the reptilian brain, the emotional arousal and fear-generating limbic brain and the slower, complex and analytical neocortical brain (36-37). In response to the activation of self-regulatory circuitry, the brain establishes a state in which a specific brain area becomes dominant (38). The actual number of brain states is not known. However, based on observed phenomena in EBT (consistent with the work of Perry investigating the effects of trauma Ultimately, this prolongs and amplifies the stress response and becomes the source of stress in its own right. It all depends on the active wiring. As illustrated in Knowing which specific symptom is involved is important in prescribing the most effective pharmacologic treatment. However, since the allostatic circuitry is not modified, the onset of another maladaptive emotional stress symptom, different from the original, may occur. Identifying the problem as a brain state of stress as opposed to just an emotional symptom of stress, may reframe the treatment plan from treating the symptoms to treating the underlying brain state, thus, reducing the risk of symptom substitution. In regards to the above described brain states, there are brain state-related characteristics in the areas of cognition (39), emotion, relation and behavior. A summary of these characteristics can be found in The stress response is organized as a survival drive. Thus, to maximize self-preservation, the brain uses generalization; as new stressors are processed they are related to previous experiences, and the existing neuronal circuits are preferentially activated and strengthened Once an allostatic state is established, the new set point is defended; the stress is preferred to well-being (homeostasis) and the allostatic brain state becomes persistent. The brain is not only stress-driven but also reward-driven. In chronic stress the eudonic rewards (41), obtained via meaning and purpose in life (i.e. happiness attained through pursuit of a virtuous life -intrinsic reward), are not accessible. Yet, reward circuits are activated to deal with the pain (both emotional and often, physical) associated with the allostatic state. Since the eudonic rewards aren't attainable, the brain defaults to accessing hedonic rewards (42-43), or pleasure for pleasure's sake (extrinsically evoked rewards). Hedonic rewards which are pleasurable (and, often, adaptive) in the short term have the potential to become repetitive, deleterious and maladaptive in the long term as the brain begins to rely on those rewards as the means for creating a pain-free life. The associations between levels of stress and maladaptive behaviors are stored in the survival brain states of 4 and 5. As the brain tends to generalize, when that level of stress is encountered, the allostatic circuit for brain state 4 or 5 is triggered and the associated maladaptive response is induced. The process is potentially repeated thousands of times over the course of a lifetime. This interpretation of maladaptive behavioral responses suggests an explanation for low adherence to behavioral recommendations seen in the current model for health care. In stress, it does not matter what the neocortex knows because the limbic and reptilian brains are dominant, set in a persistent allostatic brain state. Concept 4: We can change our wiring. Recent studies of neuroplasticity demonstrate presence/persistence of a high degree of plasticity in adult brain circuitry (44, 45) regulating motor behavior and cognition as well as emotions (46). EBT is based on positive emotional plasticity; repeated use of tools that mirror the evolutionarily-based secure at

Have I grooved to this before? Discriminating practised and observed actions in a novel context

Learning a new motor skill typically requires converting actions observed from a third-person perspective into fluid motor commands executed from a first-person perspective. In the present study, we test the hypothesis that during motor learning, the ability to discriminate between actions that have been observed and actions that have been executed is associated with learning aptitude, as assessed by a general measure of physical performance. Using a multi-day dance-training paradigm with a group of dance-naïve participants, we investigated whether actions that had been regularly observed could be discriminated from similar actions that had been physically practised over the course of three days, or a further set of similar actions that remained untrained. Training gains and performance scores at test were correlated with participants' ability to discriminate between observed and practised actions, suggesting that an individual's ability to differentiate between visual versus visuomotor action encoding is associated with general motor learning

Development of the pupillary light reflex from 9 to 24 months: association with common ASD genetic liability and 3-year ASD diagnosis

Background: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. Methods: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants. Results: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (β = −.16, 95% CI = −0.31, −0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ‘catch-up’) between 14 and 24 months relative to those with other outcomes (typical: β = .54, 95% CI = 0.08, 0.99; other: β = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (β = .08, 95% CI = 0.01, 0.14) and RRB (β = .05, 95% CI = 0.004, 0.11) traits. Conclusions: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alteration

Early development of infants with neurofibromatosis type 1: a case series

Background Prospective studies of infants at familial risk for autism spectrum disorder (ASD) have yielded insights into the earliest signs of the disorder but represent heterogeneous samples of unclear aetiology. Complementing this approach by studying cohorts of infants with monogenic syndromes associated with high rates of ASD offers the opportunity to elucidate the factors that lead to ASD. Methods We present the first report from a prospective study of ten 10-month-old infants with neurofibromatosis type 1 (NF1), a monogenic disorder with high prevalence of ASD or ASD symptomatology. We compared data from infants with NF1 to a large cohort of infants at familial risk for ASD, separated by outcome at age 3 of ASD (n = 34), atypical development (n = 44), or typical development (n = 89), and low-risk controls (n = 75). Domains assessed at 10 months by parent report and examiner observation include cognitive and adaptive function, sensory processing, social engagement, and temperament. Results Infants with NF1 showed striking impairments in motor functioning relative to low-risk infants; this pattern was seen in infants with later ASD from the familial cohort (HR-ASD). Both infants with NF1 and the HR-ASD group showed communication delays relative to low-risk infants. Conclusions Ten-month-old infants with NF1 show a range of developmental difficulties that were particularly striking in motor and communication domains. As with HR-ASD infants, social skills at this age were not notably impaired. This is some of the first information on early neurodevelopment in NF1. Strong inferences are limited by the sample size, but the findings suggest implications for early comparative developmental science and highlight motor functioning as an important domain to inform the development of relevant animal models. The findings have clinical implications in indicating an important focus for early surveillance and remediation in this early diagnosed genetic disorder

A survey on the attitudes of parents with young children on in-home monitoring technologies and study designs for infant research.

Remote in-home infant monitoring technologies hold great promise for increasing the scalability and safety of infant research (including in regard to the current Covid-19 pandemic), but remain rarely employed. These technologies hold a number of fundamental challenges and ethical concerns that need addressing to aid the success of this fast-growing field. In particular, the responsible development of such technologies requires caregiver input. We conducted a survey of the opinions of 410 caregivers on the viability, privacy and data access of remote in-home monitoring technologies and study designs. Infant-friendly wearable devices (such as sensing body suits) were viewed favourably. Caregivers were marginally more likely to accept video and audio recording in the home if data was anonymised (through automated processing) at point of collection, particularly when observations were lengthy. Caregivers were more open to international data sharing for anonymous data. Caregivers were interested in viewing all types of data, but were particularly keen to access video and audio recordings for censoring purposes (i.e., to delete data segments). Taken together, our results indicate generally positive attitudes to remote in-home monitoring technologies and studies for infant research but highlight specific considerations such as safety, privacy and family practicalities (e.g. multiple caregivers, visitors and varying schedules) that must be taken into account when developing future studies

Rewiring the stress response: A new paradigm for health care Introduction

Many diseases including obesity, irritable bowel syndrome, gastroesophageal reflux disease, depression, anxiety, chronic pain and headaches are symptoms of stress or exacerbated by stress. Stress occurs when an individual's perception or responses suggest that environmental demands tax or exceed his or her ability to cope (1). Identifying and modifying the brain circuits that trigger maladaptive stress responses should result in overall health improvement and likely decrease reliance on medications, procedures and devices. The hypothalamic-pituitary-adrenocortical axis (HPA) and the sympathetic-medullo-adrenal (SMA) system are activated in response to a stressor or fear. Their prolonged or repeated activation interferes with most physiological systems, resulting in increased risk for physical and psychiatric disorders (2-4). Links between stress and disease have been reported for depression (5-8), obesity (9-10) and cardiovascular disease (11)(12)(13)(14)(15). Each of the top ten causes of death in the United States is caused by or exacerbated by stress (16). Nationally, 75 % of adults report experiencing moderate to high levels of stress in the past month and 42 % report that their stress has increased in the past year (17). As much as 75-90 % of primary care office visits are due to symptoms that have stress related components (18). In 1979, Laurel Mellin began developing a treatment program for obesity In describing the conceptual basis of a stress intervention method, Emotional Brain Training (EBT), a program which integrates advances in neuroscience and stress physiology, we propose a new paradigm for health care. Many health care treatments focus on managing symptoms of stressrelated disorders. In modern society stress is primarily psychological in nature and in its chronic form, the result of allostatic (non-homeostatic) neural circuits that amplify and prolong stress. The result is cognitive, emotional, behavioral and physiologic dysregulation resulting in wear and tear (allostatic load). The effectiveness of treating any one stress symptom is likely decreased because of the persistent allostatic state. Emerging understanding of neuroplasticity suggests that this circuitry is capable of change. EBT is based on the repeated use of techniques that mirror secure attachment and optimal self-regulatory processing to alter allostatic circuits through the process of reconsolidation, therefore decreasing allostatic load. This results in an improved state of well-being. We hypothesize that decreased dominance of allostatic neuronal circuits leads to improved health outcomes, offering a new paradigm for health care. in the areas of neuroplasticity, emotion research, stress biology and attachment theory. The neuroscience of rewiring self-regulation utilized by EBT is based on physiologic brain states of stress. The skills used to rewire the stress response are based on four core concepts enumerated below. Concept 1: It's not us. It's our wiring. The full-blown stress response evolved in reaction to an imminent threat to survival -it is triggered rapidly and nonspecifically (22). However, this kind of threat is rare in modern society leading to an often inappropriate triggering of the full-blown stress response. The wiring that triggers this unnecessary, amplified or prolonged stress response is stored in the unconscious implicit memory systems (23) via the HPA and SMA axes (24). The self-regulatory processing is learned from parental interaction with his/her infant. In combination with genetic and environmental factors, the attachment between parent and child is encoded in the circuits of the infant's brain. This attachment is the result of the capacity of the parent to appraise the emotional state of the offspring and take necessary actions to change the child's physiology from stress to well-being, optimizing the chances for survival. Those early connections, especially before the age of three, or later in life during periods of trauma, form the basis for the circuitry of resiliency and health (25-28). These circuits may be effective or ineffective. Each new stress stimulus is compared with internal representations of past experiences stored in our memory. These representations are "archived" in neural circuits whose activation enables the brain to bring elements of past experience forward in time and to anticipate future stressors in order to respond effectively to the current milieu We hypothesize that the self-regulatory circuitry that responds to stress and reflects potentiation involves three phases: 1) quick sub-cortical processing phase (responses of the HPA and SMA axes), which is nonspecific, evolutionarily based and primarily emotive (based in fear) (34); 2) cortical/cognitive processing of emotions into conscious feelings based on expectations and past experiences -the second phase concludes with the identification of needs; 3) generation of thoughts and actions to marshal a corrective response to meet those perceived needs. The process, if adaptive, returns the person to a state of well-being. Each episode of stress may arouse self-regulatory circuitry that is an effective (adaptive) or ineffective (maladaptive) response to the stressor. The effective response or homeostatic circuit is a self-correcting, negative feedback loop, leading to a state of well-being. It triggers an emotional response that is consistent with the actual stressor, a cortical processing phase that is effective in discerning the true need based on reasonable expectations, and finally, a corrective action that returns the organism to a state of well-being, quickly and easily. Ultimately, physical, emotional, psychological and behavioral homeostasis is restored. The ineffective response (activation of an allostatic circuit) is a positive feedback loop and not self-correcting. It arouses an emotional processing that underor over-reacts to the actual stressor, a cortical processing phase that is based on unreasonable expectations and, thus, ineffective in identifying the actual need, and finally, a corrective action that does not return the person to a state of well-being. Ultimately, this prolongs and amplifies the stress response and becomes the source of stress in its own right (35). It all depends on the active wiring. Concept 2: Wiring triggers brain states. To promote the survival of the species, the brain has evolved into an organized hierarchy, which includes the simple, quick, regulatory functioning of the reptilian brain, the emotional arousal and fear-generating limbic brain and the slower, complex and analytical neocortical brain (36-37). In response to the activation of self-regulatory circuitry, the brain establishes a state in which a specific brain area becomes dominant (38). The actual number of brain states is not known. However, based on observed phenomena in EBT (consistent with the work of Perry investigating the effects of trauma Ultimately, this prolongs and amplifies the stress response and becomes the source of stress in its own right. It all depends on the active wiring. As illustrated in Knowing which specific symptom is involved is important in prescribing the most effective pharmacologic treatment. However, since the allostatic circuitry is not modified, the onset of another maladaptive emotional stress symptom, different from the original, may occur. Identifying the problem as a brain state of stress as opposed to just an emotional symptom of stress, may reframe the treatment plan from treating the symptoms to treating the underlying brain state, thus, reducing the risk of symptom substitution. In regards to the above described brain states, there are brain state-related characteristics in the areas of cognition (39), emotion, relation and behavior. A summary of these characteristics can be found in The stress response is organized as a survival drive. Thus, to maximize self-preservation, the brain uses generalization; as new stressors are processed they are related to previous experiences, and the existing neuronal circuits are preferentially activated and strengthened Once an allostatic state is established, the new set point is defended; the stress is preferred to well-being (homeostasis) and the allostatic brain state becomes persistent. The brain is not only stress-driven but also reward-driven. In chronic stress the eudonic rewards (41), obtained via meaning and purpose in life (i.e. happiness attained through pursuit of a virtuous life -intrinsic reward), are not accessible. Yet, reward circuits are activated to deal with the pain (both emotional and often, physical) associated with the allostatic state. Since the eudonic rewards aren't attainable, the brain defaults to accessing hedonic rewards (42-43), or pleasure for pleasure's sake (extrinsically evoked rewards). Hedonic rewards which are pleasurable (and, often, adaptive) in the short term have the potential to become repetitive, deleterious and maladaptive in the long term as the brain begins to rely on those rewards as the means for creating a pain-free life. The associations between levels of stress and maladaptive behaviors are stored in the survival brain states of 4 and 5. As the brain tends to generalize, when that level of stress is encountered, the allostatic circuit for brain state 4 or 5 is triggered and the associated maladaptive response is induced. The process is potentially repeated thousands of times over the course of a lifetime. This interpretation of maladaptive behavioral responses suggests an explanation for low adherence to behavioral recommendations seen in the current model for health care. In stress, it does not matter what the neocortex knows because the limbic and reptilian brains are dominant, set in a persistent allostatic brain state. Concept 4: We can change our wiring. Recent studies of neuroplasticity demonstrate presence/persistence of a high degree of plasticity in adult brain circuitry (44, 45) regulating motor behavior and cognition as well as emotions (46). EBT is based on positive emotional plasticity; repeated use of tools that mirror the evolutionarily-based secure at