the impact of a specific threat is defined as

Huggenvik, J. I. et al. 4, 35 (2010). Wilson, C. B., Ebenezer, P. J., McLaughlin, L. D. & Francis, J. The Family Nurse Partnership blog page includes various posts on mental health, child development, domestic violence and more. This framework links directly to the guidelines. Kilpatrick, D. G. et al. Biochem. and JavaScript. Future preclinical studies can further elucidate the impact of differences in trauma type and extent of exposure on changes in the expression of 5-HT1A and other molecular targets by consciously and deliberately accounting for trauma type. & Padovan, C. Role of serotonin 1A receptors in the median raphe nucleus on the behavioral consequences of forced swim stress. CAS J. Pathophysiol. Neuropharmacology 62, 177183 (2012). Brain Res. Well send you a link to a feedback form. Google Scholar. Goldsmith, R. E., Freyd, J. J. Transl. Cooper, M. A., Grober, M. S., Nicholas, C. & Huhman, K. L. Aggressive encounters alter the activation of serotonergic neurons and the expression of 5-HT1A mRNA in the hamster dorsal raphe nucleus. For example, if Threat #1 (Fire) is mapped to a specific vulnerability, the threat impact areas are Denial of Service and Destruction. For example, good communication can reveal more clues, which may open up more avenues for investigation (curiosity). This framework is based on the Colleges 10 principles of risk. Eur. Rep. 8, 14082 (2018). 24, 410419 (2014). Trauma informed practice is an approach which is grounded in the understanding that trauma exposure can impact an individuals neurological, biological, psychological and social development thus shaping a persons world view and relationship development. The impact of a specific threat is defined as: a. Google Scholar. No child left behind is a public health informed approach focused on improving outcomes for vulnerable children. Front. Trauma and PTSD in the WHO world mental health surveys. Poulos, C. X., Parker, J. To aid the understanding of this guidance we have defined some of the terms used. For example, exposure to CUS led to multiple region-specific increases and decreases in dopamine D1-like receptor binding, but exposure to RS did not impact D1-like receptor binding in any of those regions145. 19, 23932420 (2019). We propose that these two approaches need not be mutually exclusive. Specific data sets relating to risk factors, protective factors and outcomes are available on fingertips a large public health data collection. Evaluating risk decisions should focus on the quality of the decision making, not the outcome. Jovanovic, H., Perski, A., Berglund, H. & Savic, I. Our #CyberChoices campaign encouraged parents of young people with cyber skills to talk to them about their ambitions and the opportunities to use their skills positively. Chem. 48, 738754 (2011). Google Scholar. Click on the button below to view all vacancies. For example, preclinical studies suggest that biased 5-HT1A agonists, which specifically target autoreceptor or heteroreceptor signaling, may be more effective in treating depression and anxiety than currently available 5-HT1A agonists133,134,135. Am. The framework for support from the broader system can be understood as operating at three levels. Pharmacol. Rev. Psychiatry 22, 519 (2017). Paskitti, M., McCreary, B. Biased agonism at serotonin 5-HT1A receptors: preferential postsynaptic activity for improved therapy of CNS disorders. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. In one study, exposure to RS led to reduced Freud-1 mRNA and protein in the prefrontal cortex as well as the expected concurrent increase in prefrontal 5-HT1A mRNA in Sprague-Dawley rats123. Psychiatry 1, 11351156 (2018). Ferretti, C., Blengio, M., Gamalero, S. R. & Ghi, P. Biochemical and behaviour changes induced by acute stress in a chronic variate stress model of depression: the effect of amitriptyline. Blackpool Better Start developed a good practice guide to support the implementation of trauma informed care in the perinatal period for all staff working with perinatal women in maternity and mental health services, although it may be more pertinent to certain roles. & Gthert, M. 5-HT receptor regulation of neurotransmitter release. Curr. Ther. Studies from the preclinical and human literature suggest that dysfunctional expression of 5-HT1A is associated with a multitude of psychiatric symptoms commonly seen in trauma-exposed individuals. Rev. However, the prevailing consensus is that 5-HT1A is influential in the development of depression, anxiety, fear, and memory impairment35,36,37. & Albert, P. R. Region-specific regulation of 5-HT1A receptor expression by Pet-1-dependent mechanisms in vivo. To better inform professional judgement, the three guidelines should be applied in combination, not in isolation. Neurobiol. Brain Res. Psychoneuroendocrinology 35, 15531564 (2010). Childhood maltreatment experiences are associated with altered diffusion in occipito-temporal white matter pathways. Milak, M. S. et al. These encounters may also reveal vulnerabilities. Neuropsychopharmacol. Wilson, M. A., Grillo, C. A., Fadel, J. R. & Reagan, L. P. Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala. Acad. 91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110). They may avoid certain situations out of worry. Qualitative risk analysis refers to the risk analysis tools and techniques that rely on expert subject matter opinions, subjective and non-statistical means to assess the likelihood and impact of project risks. Risk = (Threat x Vulnerabilities) x Impact. broad domains; the two sub-bullets in the risk definition further clarify its use in those two domains. Though any number of molecular targets could theoretically be used to demonstrate this principle, 5-HT1A was used in this article for both practical and theory-driven reasons. Furthermore, they provide insight into the fact that traumatic stressors may regulate a wide array of molecular targets through diffusely acting mechanisms. Okamoto, S.-I., Sherman, K., Bai, G. & Lipton, S. A. Over the last decade, responders have been reliant on checklists and risk tools to identify and assess risk. Trauma results from an event, series of events or set of circumstances that is experienced by an individual as physically or emotionally harmful, or life threatening. Pharmacol. Ford, J. D., Stockton, P., Kaltman, S. & Green, B. L. Disorders of extreme stress (DESNOS) symptoms are associated with type and severity of interpersonal trauma exposure in a sample of healthy young women. Single prolonged stress: toward an animal model of posttraumatic stress disorder. For example, the 5-HT1A repressor Freud-1 also represses the dopamine receptor D2154. The concurrent nature of these changes in 5-HT1A mRNA and 5-HT1A protein expression suggests that transcriptional mechanisms are at least partially responsible for the observed change in 5-HT1A expression in these studies. Differences in chronicity of trauma exposure can differentially impact 5-HT1A expression in complex ways. Without longitudinal data it is not possible to determine whether dysregulated 5-HT1A expression occurred as a result of stress exposure (traumatic or otherwise) or represents a preexisting risk factor for stressor-induced disorders. In addition, one study finds that individuals with PTSD may have elevated 5-HT1A availability76. Can. J. Psychiatry 155, 714 (1989). This review focuses on the importance of considering differences in the nature and chronicity of trauma exposure in neurobiological research. The cost of recovering the asset b. Varlinskaya, E. I., Johnson, J. M., Deak T. & Diaz M. R. Adolescent forced swim stress increases social anxiety-like behaviors and alters the dynorphin/kappa opioid receptor system in the basolateral amygdala of males. 264, 7684 (2018). Child Abuse Negl. A prerequisite in the analysis of threats is the understanding of the generic definition of risk. Criminals and the technical infrastructure they use are often based overseas, making international collaboration essential. 7, 24 (2014). & Vahid-Ansari, F. Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm. A risk has a cause and, if it occurs, an impact. Shavitt, R. G. et al. Psychiatry 49, 132140 (2010). 39), suicide (for review, see Ref. Behav. Sch. Collectively, these findings suggest that the impact of trauma exposure on 5-HT1A expression is dependent, in part, on trauma type and extent of exposure. However, targeting the correct mechanism for alteration of 5-HT1A may be critical44,136. A closer examination of specific mechanisms of 5-HT1A alterations provides a useful paradigm for understanding the complexity of the concurrent impact of different trauma types and degrees of . This could be about sharing what has worked well in order to benefit your colleagues and local people, or help you with your professional development. Front. 104, 283920 (2011). Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H] WAY-100635 and [11C] way-100635. 156, 700708 (2011). 48, 296 (2016). 39, 75517563 (2019). Dont include personal or financial information like your National Insurance number or credit card details. While it seems clear based on the reviewed preclinical literature that trauma type and chronicity of exposure impact gene expression, no available preclinical studies examining 5-HT1A distinguish behaviorally affected and resilient individuals. Rev. 121, 462470 (2010). Furthermore, research suggests that genetic risk for PTSD covaries with trauma type, timing, severity, and degree of exposure22,23,24,25,26,27,28. & Schtzwohl, M. Trauma severity and initial reactions as precipitating factors for posttraumatic stress symptoms and chronic dissociation in former political prisoners. In addition to qualitative differences, preclinical trauma models can vary in duration (time per exposure) and chronicity (days of exposure)83. In addition, none have accounted for trauma type. spot the clues associated with vulnerability-related risk, create an environment that encourages individuals to disclose relevant information, be curious and obtain a rich picture of circumstances associated with an incident, practitioner expertise, including face-to-face interviews and calls for practice, generally applicable suggestions extracted from existing guidance on achieving best evidence, relevant information from the research evidence. Rojas, P. S. & Fiedler, J. L. What do we really know about 5-HT1A receptor signaling in neuronal cells? Special issues are commonly defined as "a journal issue either completely or partly devoted . Luo, F. F., Han, F. & Shi, Y. X. Brain Res. What Is Qualitative Risk Analysis? Artigas, F., Celada, P. & Bortolozzi, A. Kaur, G. & Kulkarni, S. Differential effect of a polyherbal formulation-OB-200G in male and female mice subjected to forced swim stress. Soc. Read our privacy policy for more information on how we use this data. & Kung, Y. W. Attachment dimensions and post-traumatic symptoms following interpersonal traumas versus impersonal traumas in young adults in Taiwan. Though the preclinical literature is consistent in suggesting that trauma alters 5-HT1A expression, specific findings diverge; some studies have observed increasing expression41, while others have observed the opposite42. Smith, H. L., Summers, B. J., Dillon, K. H. & Cougle, J. R. Is worst-event trauma type related to PTSD symptom presentation and associated features? For example, in rodents, the 5-HT1A agonist 8-OH-DPAT has been found to increase impulsive action at low doses, and decrease impulsive action at higher doses59. Behav. Vulnerable background Children and young people's physical, emotional and mental wellbeing are significantly shaped by the social determinants of health into which they are born, live, learn and. Biochem. Psychiatry Res. Neurosci. Consult Clin. Neurobiol. & Seckl, J. R. Acute restraint stress increases 5-HT7 receptor mRNA expression in the rat hippocampus. Google Scholar. We have also developed close and effective partnerships with private industry to share information and technical expertise. J. Psychiatry 162, 383385 (2005). What is defined as specific avenues that threat agents can exploit to attack an information asset? Does one size fit all? Having an awareness of vulnerabilities when providing healthcare is about more than access to health or care. Neurosci. Officers and staff who are involved in these roles may also find a number of the guidelines relevant to their role. J. Trauma Stress. 100, 1429314296 (2003). To date, very few published studies have directly examined the association between trauma exposure and 5-HT1A expression in humans. 46, 327343 (2016). These initial police interactions present crucial opportunities for appropriate action, for example, safeguarding. Behav. Differential response of central dopaminergic system in acute and chronic unpredictable stress models in rats. The calculation, therefore, is 27*2*2*5=540. Complex PTSD, interpersonal trauma and relational consequences: findings from a treatment-receiving Northern Irish sample. The long-term behavioral, psychological, and neurobiological effects of exposure to potentially traumatic events vary within the human population. PubMed A vulnerability is any weakness (known or unknown) in a system, process, or other entity that could lead to its security being compromised by a threat. J. Psychotraumatol. Risk and protective factors can be found in every area of a child or adolescents life, exerting different effects at different stages of development. In addition, one study found that the 5-HT1A agonist 8-OH-DPAT attenuated the corticosterone response to FC but not RS or IES (approximates exposure to inescapable physical harm)128. . 53, 40264033 (2016). To help us improve GOV.UK, wed like to know more about your visit today. 8, 12 (2010). PubMed Central Decision makers are required to consider the value and likelihood of a decisions possible benefits against the seriousness and likelihood of the harm (. Child Adolesc. This can perpetuate inequality throughout life and from one generation to the next. Mendelson, S. D. & McEwen, B. S. Autoradiographic analyses of the effects of restraint-induced stress on 5-HT1A, 5-HT1C and 5-HT2 receptors in the dorsal hippocampus of male and female rats. & Herman, J. Briones-Aranda, A., Rocha, L. & Picazo, O. Ito, H., Halldin, C. & Farde, L. Localization of 5-HT1A receptors in the living human brain using [carbonyl-11C] WAY-100635: PET with anatomic standardization technique. In order to respond effectively to a persons vulnerabilities, and to manage them so they do not suffer harm, it is necessary to have an assessment of the capacity and resilience of that individual, as well as the people around them. 615, 8794 (1993). Should posttraumatic stress be a disorder or a specifier? This does not mean that every child experiencing trauma and adversity will experience poorer outcomes. Of note, however, trauma type was not controlled for and authors acknowledged that the study may have lacked sufficient power to detect an association185. As is the case with different types of traumas, preclinical results suggest that, when controlling for all other factors, differences in duration (time per exposure) or chronicity (days of exposure) lead to different alterations in 5-HT1A expression and 5-HT1A mRNA expression. Qi, X., Lin, W., Li, J., Pan, Y. Psychopharmacology 236, 29832995 (2019). Synapse 53, 1119 (2004). & Runtz, M. Differential adult symptomatology associated with three types of child abuse histories. Sullivan, G. M. et al. J. Behav. Pham. To date, models of early life trauma have been associated with increases183, decreases174, or no change184 in 5-HT1A expression. Flibanserin and 8-OH-DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair-bond quality. Xiang, M. et al. Cyber criminals seek to exploit human or security vulnerabilities in order to steal passwords, data or money directly. Affect. J. Neural Transm. Future studies should apply methodology such as cut-off behavioral criteria and behavioral profiling in order to distinguish alterations in 5-HT1A that are seen in resilient animals from those seen in affected animals. Google Scholar. Resilient individuals, families and communities are more able to deal with difficulties and adversities than those with less resilience. Dis. To view this licence, visit nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gov.uk. Many definitions of vulnerability and vulnerable populations already exist with differing perspectives or contexts depending on the setting and experiences. Natl Acad. This evidence base is reflected in three responder-focused guidelines clues, communication and curiosity. B Neuropsychiatr. Risk factors can increase the likelihood that a person may become vulnerable, however they may be a contributing factor and not necessarily a direct cause. NHS England have developed a good practice guide to support implementation of trauma informed care in the perinatal period. Article More studies are needed in order to identify relationships between specific categories of trauma and resultant alterations in gene expression. Posttranscriptional mechanisms include any process after the transcription of DNA into mRNA, which affect subsequent steps of gene expression120. Genet. Psychiatry Rep. 19, 66 (2017). Osei-Owusu, P., James, A., Crane, J. Being trauma informed means assuming that people are more likely than not to have a history of traumatic experiences, and that these experiences may impact on their ability to feel safe within or develop trusting relationships with services and their staff. Immobility behavior during the forced swim test correlates with BNDF levels in the frontal cortex, but not with cognitive impairments. Chen, Y. et al. 108, 311319 (2001). Taken as a whole, this evidence suggests that the impact of trauma exposure on 5-HT1A expression, including the region, direction, and mechanism of change, is influenced by and potentially dependent in part on the type of trauma an individual is exposure to. 3. Similarly, findings from two studies suggest that exposure to 14 days of CUS led to a decrease in hippocampal 5-HT1A mRNA expression, but exposure to 7 days of the same CUS paradigm did not alter hippocampal 5-HT1A mRNA expression42,119. The role of the committee was to develop the scope, consider the evidence and draft the guidelines, taking into account the views of stakeholders. As mentioned previously, qualitatively different types of traumas can produce distinct neurobiological and behavioral consequences (e.g., Ref. Dorahy, M. J. et al. Exp. The region-specific nature of the physiological effects of 5-HT1A may be relevant to its impact on adaptive and maladaptive behaviors. Future studies should examine the degree to which the interaction of stressor type and sex extends to rodent trauma models and human trauma exposure. Psychiatry 34, 2275 (2009). Exposure factor is defined as: a. B., Bondar, N. P., Filipenko, M. L. & Kudryavtseva, N. N. Downregulation of serotonergic gene expression in the Raphe nuclei of the midbrain under chronic social defeat stress in male mice. Transgenerational disruption of functional 5-HT 1A R-induced connectivity in the adult mouse brain by traumatic stress in early life. These results support a possible region-specific dose-response relationship between chronicity of trauma exposure and 5-HT1A binding. The cost of late intervention is estimated at 16.6 billion a year. Flgge, G., Kramer, M., Rensing, S. & Fuchs, E. 5HT1A-receptors and behaviour under chronic stress: selective counteraction by testosterone. Amir, M., Kaplan, Z. Weissmann-Nanopoulos, D., Mach, E., Magre, J., Demassey, Y. Child Psychol. Shirk, S. R. & Karver, M. Prediction of treatment outcome from relationship variables in child and adolescent therapy: a meta-analytic review. Saphier, D., Farrar, G. E. & Welch, J. E. Differential inhibition of stress-induced adrenocortical responses by 5-HT1A agonists and by 5-HT2 and 5-HT3 antagonists. Psychopharmacology 231, 623636 (2014). Of note, in CSD-exposed voles, 5-HT1A autoreceptor expression was increased in the dorsal raphe nucleus (which projects to the PrL), suggesting that the decreased PrL serotonin levels were caused by a region-specific increase in 5-HT1A expression130. Behav. Cell. 14, 357364 (1990). Immun. April 14, 2023 Reviewed by Saul Mcleod, PhD Key Points Stereotype threat refers to the psychological phenomenon where an individual feels at risk of confirming a negative stereotype about a group they identify with. Guina, J. et al. Psychoneuroendocrinology 20, 239257 (1995). Eur. Trauma 10, 345 (2018). Anderson, R. I., Lopez, M. F. & Becker, H. C. Forced swim stress increases ethanol consumption in C57BL/6J mice with a history of chronic intermittent ethanol exposure. 40), substance abuse (e.g., Ref. The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Mol. Vulnerability may be temporal in nature, so specific populations may be at greater risk of poor health outcomes in times of crisis. 8, 1353383 (2017). White Ribbon UK is the leading charity engaging with men and boys to end violence against women they provide reports and resources on tackling violence. Mol. In addition, 5-HT1A promotors MAZ and Sp1 decrease NMDA receptor subunit type 1 promoter activity158,159. We recognise that health and care staff as individuals may also experience similar issues in their personal lives. Brain Res. You can change your cookie settings at any time. Given the impact of trauma type and extent of exposure on 5-HT1A, we theorize that trauma history may be a crucial determinant of response to future breakthrough treatments. Towards improved nosology within the DSM categorical classification system. Trauma types as differential predictors of posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and their comorbidity. Brain Behav. 48, 1321 (2013). We have seen a significant growth in cyber criminality in the form of high-profile ransomware campaigns over the last year. Controversies regarding the use of a binary definition of trauma, which may incorrectly exclude some extreme stressors while incorrectly amalgamating others, have led to calls for a more fine-grained approach80. Steciuk, M., Kram, M., Kramer, G. L. & Petty, F. Acute stress does not alter 5-HT1A receptor density. Sniecikowska, J., Newman-Tancredi, A. A risk matrix is a typical example of a qualitative risk analysis tool. Exposure to potentially traumatic events in early childhood: differential links to emergent psychopathology. Liu, Y., Beyer, A. PubMed Central Ability, gaps, needs, opportunities, barriers and constraints to predicting climate variability, impacts and . Hum. The approach considers both the adversities people experience and factors likely to make them more vulnerable to poor outcomes. Briggs-Gowan, M. J. et al. Lin, L., Liu, G. & Zhang, Y. Brain Res. Qi, X. et al. For the guidelines to be implemented effectively, there must be suitable professional development opportunities for all staff. Kondam, A., Kate, N. N. & Lakshmi, G. Effect of forced swim stress on wistar albino rats in various behavioral parameters. Pharmacol. Annu. 107, abstr. Eur. The aim of these guidelines is to support all officers and staff to: This will help responders to deliver an appropriate policing response, irrespective of crime or incident type. The part of an asset's value that is likely to be lost by a particular threat b. CAS This approach could also be extended to other relevant risk factors, such as inherited genetic differences, which are shown to alter traumas impact on 5-HT1A expression as well as behavior182. They are supported by families, friends and communities to different levels. Due to the multifaceted and heterogeneous nature of potentially traumatic events, previous reviews have stated that no single preclinical model of trauma can adequately capture all aspects of trauma and that an ideal approach should draw from a variety of distinct models82,83. Psychiatry 43, 547573 (1998). & Binder, E. Geneenvironment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism. Neurochem. Yamamoto, M. et al. J. Trauma Stress. Kim, M. H. & Leem, Y. H. Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and cAMP signaling in hippocampus. Regarding the overall frequency of pro-social behavior, 8-OH-DPAT led to an increase, MDL-73,005-EF led to a decrease, and ipsapirone had no effect64. Thus, we examine the literature on 5-HT1A as an exemplar of a more general observation: in order to understand the neurobiology of trauma, one must account for covariance of trauma type and neurobiological alterations. Child Adolesc. Hourglass is a national charity with a mission to end the harm of older people in the UK. Building on (Pearl [2001]), I explicate the notion of a path-specific effect. Because the distinction between nation states and criminal groups is increasingly blurred, cyber crime attribution is sometimes difficult. Cognitive behavioural manipulation of people or specific vulnerable . Huang, Y. L., Chen, S. H., Su, Y. J. Res. . . Proc. A., Caldas, S. V., Dolan, M., Lagdon, S. & Armour, C. PTSDs factor structure and measurement invariance across subgroups with differing count of trauma types. 109). Psychiatry 6, e799 (2016). For example, in one study, exposure to CSD led to a transient increase in 5-HT1A binding in the claustrum, which was found when exposure lasted 2 days, but not when exposure lasted 10 or more days43. J. Med. Effect of the ubiquitous transcription factors, SP1 and MAZ, on NMDA receptor subunit type 1 (NR1) expression during neuronal differentiation. J. Med. Rev. Vzquez, D. M., Eskandari, R., Zimmer, C. A., Levine, S. & Lpez, J. F. Brain 5-HT receptor system in the stressed infant rat: implications for vulnerability to substance abuse. J. Trauma Stress 13, 651660 (2000). Psychiatry 45, 934937 (1999). These 2 courses equip staff, volunteers and community members to provide practical and emotional support, as well as recognising people at risk of distress: Staff members should consider their own wellbeing and need for support, including accessing supervision where available. Individuals will process traumatic events in different ways as a result of the interaction between their own neurobiology, previous experiences of trauma and the type of support available to them, as well as the broader social context in which they live. Yau, J. L., Noble, J. The 5-HT1A receptor is one of seven inhibitory G protein-coupled serotonin receptors and is encoded by the HTR1A gene44. ISSN 2158-3188 (online), Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT1A expression, https://doi.org/10.1038/s41398-020-00915-1, https://doi.org/10.1016/j.celrep.2020.107716, http://creativecommons.org/licenses/by/4.0/, Cancel gren, S. O. et al. The committee was supported by College of Policing specialist staff. A multitude of preclinical and human studies have linked 5-HT1A expression and activation to a number of well-known trauma sequalae; examples include depression (for reviews, see Refs. As health and care professionals, having an awareness that this impact is not always visible and understanding how best to support individuals accessing services who may be vulnerable, will enable care to be provided that is accessible, appropriate and effective. This guide is part of All Our Health, a resource which helps health professionals provide better access to health and care, and promote wellbeing as part of their everyday practice. Article & Schmidt, M. V. Animal models of PTSD: a challenge to be met. For example, in one study, exposure to 30min of FS led to an increase in 5-HT1A agonist binding and 5-HT1A antagonist binding in the hippocampus and cortex124. Notably, the results of some PET studies have been shown to vary as a function of which outcome measure researchers employ.

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