Reducing meat consumption may improve human health, curb environmental damage, and limit the large-scale suffering of animals reared in factory farms. Most attention to reducing consumption has focused on restructuring environments where foods are chosen or making health or environmental appeals. However, psychological theory suggests that interventions appealing to animal welfare might operate on distinct, potent pathways. We conducted a systematic review and meta-analysis evaluating the effectiveness of these interventions. We searched eight academic databases and extensively searched grey literature. We meta-analyzed 100 studies assessing interventions designed to reduce meat consumption or purchase by mentioning or portraying farm animals, that measured behavioral or self-reported outcomes related to meat consumption, purchase, or related intentions, and that had a control condition. The interventions consistently reduced meat consumption, purchase, or related intentions at least in the short term with meaningfully large effects (meta-analytic average risk ratio [RR] = 1.22; 95% CI: [1.13, 1.33]). We estimated that a large majority of true population effects (71%; [95% CI: 58%, 80%]) were stronger than RR=1.1 and that few were in the unintended direction. Via meta-regression, we identified some study and intervention characteristics that were associated with effect size. Risk-of-bias assessments identified both methodological strengths and limitations of this literature; however, results did not differ meaningfully in sensitivity analyses retaining only studies at the lowest risk of bias. Evidence of publication bias was not apparent. In conclusion, animal welfare interventions preliminarily appear effective in these typically short-term studies of primarily self-reported outcomes. Future research should use direct behavioral outcomes that minimize the potential for social desirability bias and are measured over long-term follow-up.

Android robots that are close, but imperfect, likenesses of humans can provoke negative feelings of dislike and eeriness in humans (“Uncanny Valley” effect). We investigated whether category confusion between the perceptual categories of “robot” and “human” contributes to Uncanny Valley aversion. Using a novel, validated corpus of 182 images of real robot and human faces, we precisely estimated the shape of the Uncanny Valley and the location of the perceived robot/human boundary. To implicitly measure confusion, we tracked 358 subjects’ mouse trajectories as they categorized the faces. We observed a clear Uncanny Valley and a pattern of categorization supporting a perceived categorical boundary. Yet, in contrast to predictions of the category confusion mechanism hypothesis, the Uncanny Valley and category boundary locations did not coincide, and mediation analyses further failed to support a causal role of category confusion. These results suggest category confusion does not explain the Uncanny Valley effect.

BACKGROUND:Reducing meat consumption may improve human health, curb environmental damage and greenhouse gas emissions, and limit the large-scale suffering of animals raised in factory farms. Previous work has begun to develop interventions to reduce individual meat consumption, often by appealing directly to individual health motivations. However, research on nutritional behavior change suggests that interventions additionally linking behavior to ethical values, identity formation, and existing social movements may be particularly effective and longer-lasting. Regarding meat consumption, preliminary evidence and psychological theory suggest that appeals related to animal welfare may have considerable potential to effectively leverage these elements of human psychology. We aim to conduct a systematic review and quantitative meta-analysis evaluating the effectiveness of animal welfare-related appeals on actual or intended meat consumption or purchasing. Our investigation will critically synthesize the current state of knowledge regarding psychological mechanisms of intervening on individual meat consumption and empirically identify the psychological characteristics underlying the most effective animal welfare-based interventions. METHODS:We will systematically search eight academic databases and extensively search unpublished grey literature. We will include studies that assess interventions intended to reduce meat consumption or purchase through the mention or portrayal of animal welfare, that measure outcomes related to meat consumption or purchase, and that have a control condition. Eligible studies may recruit from any human population, be written in any language, and be published or released any time. We will meta-analyze the studies, reporting the pooled point estimate and additional metrics that describe the distribution of potentially heterogeneous effects. We will assess studies' risk of bias and conduct sensitivity analyses for publication bias. We describe possible follow-up analyses to investigate hypothesized moderators of intervention effectiveness. DISCUSSION:The findings of the proposed systematic review and meta-analysis, including any identified methodological limitations of the existing literature, could inform the design of successful evidence-based interventions with broad potential to improve human, animal, and environmental well-being. SYSTEMATIC REVIEW REGISTRATION:The protocol was preregistered via the Open Science Framework (https://osf.io/d3y56/registrations).

Mouse-tracking is a sophisticated tool for measuring rapid, dynamic cognitive processes in real time, particularly in experiments investigating competition between perceptual or cognitive categories. We provide user-friendly, open-source software ( https://osf.io/st2ef/ ) for designing and analyzing such experiments online using the Qualtrics survey platform. The software consists of a Qualtrics template with embedded JavaScript and CSS along with R code to clean, parse, and analyze the data. No special programming skills are required to use this software. As we discuss, this software could be readily modified for use with other online survey platforms that allow the addition of custom JavaScript. We empirically validate the provided software by benchmarking its performance on previously tested stimuli (android robot faces) in a category-competition experiment with realistic crowdsourced data collection.

Android robots are entering human social life. However, human-robot interactions may be complicated by a hypothetical Uncanny Valley (UV) in which imperfect human-likeness provokes dislike. Previous investigations using unnaturally blended images reported inconsistent UV effects. We demonstrate an UV in subjects' explicit ratings of likability for a large, objectively chosen sample of 80 real-world robot faces and a complementary controlled set of edited faces. An "investment game" showed that the UV penetrated even more deeply to influence subjects' implicit decisions concerning robots' social trustworthiness, and that these fundamental social decisions depend on subtle cues of facial expression that are also used to judge humans. Preliminary evidence suggests category confusion may occur in the UV but does not mediate the likability effect. These findings suggest that while classic elements of human social psychology govern human-robot social interaction, robust UV effects pose a formidable android-specific problem.

Acute insults produce hyperalgesic priming, a neuroplastic change in nociceptors that markedly prolongs inflammatory mediator-induced hyperalgesia. After an acute initiating insult, there is a 72 h delay to the onset of priming, for which the underlying mechanism is unknown. We hypothesized that the delay is due to the time required for a signal to travel from the peripheral terminal to the cell body followed by a return signal to the peripheral terminal. We report that when an inducer of hyperalgesic priming (monocyte chemotactic protein 1) is administered at the spinal cord of Sprague Dawley rats, priming is detected at the peripheral terminal with a delay significantly shorter than when applied peripherally. Spinally induced priming is detected not only when prostaglandin E-2 (PGE(2)) is presented to the peripheral nociceptor terminals, but also when it is presented intrathecally to the central terminals in the spinal cord. Furthermore, when an inducer of priming is administered in the paw, priming can be detected in spinal cord (as prolonged hyperalgesia induced by intrathecal PGE(2)), but only when the mechanical stimulus is presented to the paw on the side where the priming inducer was administered. Both spinally and peripherally induced priming is prevented by intrathecal oligodeoxynucleotide antisense to the nuclear transcription factor CREB mRNA. Finally, the inhibitor of protein translation reversed hyperalgesic priming only when injected at the site where PGE(2) was administered, suggesting that the signal transmitted from the cell body to the peripheral terminal is not a newly translated protein, but possibly a newly expressed mRNA.

The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment. Inevitably, transformative progress in this field will require a better understanding of the functional links among the ever-growing ranks of "pain molecules," as well as their links with an even larger number of molecules with which they interact. Importantly, all of these molecules exist side-by-side, within a functional unit, the cell, and its adjacent matrix of extracellular molecules. To paraphrase a recent editorial in Science magazine [223], although we live in the Golden age of Genetics, the fundamental unit of biology is still arguably the cell, and the cell is the critical structural and functional setting in which the function of pain-related molecules must be understood. This review summarizes our current understanding of the nociceptor as a cell-biological unit that responds to a variety of extracellular inputs with a complex and highly organized interaction of signaling molecules. We also discuss the insights that this approach is providing into peripheral mechanisms of chronic pain and sex dependence in pain.

Chronic peripheral neuropathic pain is the result of abnormal activity in sensory nerves. It is well recognized that this sensory nerve dysfunction can be caused by traumatic, toxic, or metabolic insult to the nerve. In addition, there is growing recognition that neuropathic pain is a frequent manifestation of neurodegenerative diseases. In this regard, important clues to the cellular mechanisms of neuropathic pain may be found by close examination of neurodegenerative diseases (including Parkinson's disease) in which neuropathic pain is often an underappreciated but important clinical manifestation. This approach identifies specific mitochondrial and cytoskeletal mechanisms, previously implicated in the pathophysiology of neurodegenerative diseases in the central nervous system, that might contribute to neuropathic dysfunction in peripheral sensory nerve fibers. Investigations in preclinical models of common peripheral neuropathic pain conditions have supported the idea that a subset of these cellular mechanisms of neurodegeneration can produce painful hyperactivity in primary afferent nociceptors. Importantly, this emerging concept of neurodegenerative disease mechanisms in the primary afferent nociceptor identifies novel molecular targets for the treatment neuropathic pain. Ann Neurol 2011;69:13–21

While oxidative stress has been implicated in small-fiber painful peripheral neuropathies, antioxidants are only partially effective to treat patients. We have tested the hypothesis that Drp1 (dynamin-related protein 1), a GTPase that catalyzes the process of mitochondrial fission, which is a mechanism central for the effect and production of reactive oxygen species (ROS), plays a central role in these neuropathic pain syndromes. Intrathecal administration of oligodeoxynucleotide antisense against Drp1 produced a decrease in its expression in peripheral nerve and markedly attenuated neuropathic mechanical hyperalgesia caused by HIV/AIDS antiretroviral [ddC (2′,3′-dideoxycytidine)] and anticancer (oxaliplatin) chemotherapy in male Sprague Dawley rats. To confirm the role of Drp1 in these models of neuropathic pain, as well as to demonstrate its contribution at the site of sensory transduction, we injected a highly selective Drp1 inhibitor, mdivi-1, at the site of nociceptive testing on the dorsum of the rat's hindpaw. mdivi-1 attenuated both forms of neuropathic pain. To evaluate the role of Drp1 in hyperalgesia induced by ROS, we demonstrated that intradermal hydrogen peroxide produced dose-dependent hyperalgesia that was inhibited by mdivi-1. Finally, mechanical hyperalgesia induced by diverse pronociceptive mediators involved in inflammatory and neuropathic pain—tumor necrosis factor α, glial-derived neurotrophic factor, and nitric oxide—was also inhibited by mdivi-1. These studies provide support for a substantial role of mitochondrial fission in preclinical models of inflammatory and neuropathic pain.

Clinical pain conditions may remain responsive to opiate analgesics for extended periods, but such persistent acute pain can undergo a transition to an opiate-resistant chronic pain state that becomes a much more serious clinical problem. To test the hypothesis that cellular mechanisms of chronic pain in the primary afferent also contribute to the development of opiate resistance, we used a recently developed model of the transition of from acute to chronic pain, hyperalgesic priming. Repeated intradermal administration of the potent and highly selective mu-opioid agonist, [d-Ala(2),N-MePhe(4),gly-ol]-enkephalin (DAMGO), to produce tolerance for its inhibition of prostaglandin E(2) hyperalgesia, simultaneously produced hyperalgesic priming. Conversely, injection of an inflammogen, carrageenan, used to produce priming produced DAMGO tolerance. Both effects were prevented by inhibition of protein kinase Cepsilon (PKCepsilon). Carrageenan also induced opioid dependence, manifest as mu-opioid receptor antagonist (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2))-induced hyperalgesia that, like priming, was PKCepsilon and G(i) dependent. These findings suggest that the transition from acute to chronic pain, and development of mu-opioid receptor tolerance and dependence may be linked by common cellular mechanisms in the primary afferent.

Background: State and national policymakers are actively debating the merits of legally mandating the human papillomavirus (HPV) vaccine.Methods: This was a cross-sectional pilot study designed to identify factors associated with HPV vaccination in 170 high school girls and the decision making by girls about vaccination.Results: Overall, 48.4% participated in the vaccination decision making and 37.8% were vaccinated, but there were significant vaccine-related knowledge gaps. Girls often lacked basic knowledge necessary to make vaccine decisions. Vaccination was significantly associated with older age, vaccine information sources, and higher vaccine-related knowledge, but not with estimates of risk of HPV-related diseases, religion, or frequency of health care visits.Conclusions: This paper describes the first study to have identified factors associated with HPV vaccination among California high school girls and to have documented that a high percentage are participating in the vaccination decision making. These findings have implications for adolescent health education and nursing practice and provide new information relevant to the current public policy debates about mandatory vaccination. J Pediatr Health Care. (2010) 24, 14-24.

The transition from acute to chronic pain states might be the most important challenge in research to improve clinical treatment of debilitating pain. We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines. This phenomenon, "hyperalgesic priming," depends on the epsilon isoform of protein kinase C (PKCepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability. We discuss the impact of this discovery on our understanding of, and ultimately our ability to treat, a variety of enigmatic and debilitating pain conditions, including those associated with repetitive injury, and generalized pain conditions, such as fibromyalgia.

Purpose: To identify factors associated with receipt of the human papilloma virus (HPV) vaccine by high school girls and the decision-making by girls about vaccination. Methods: This was a two-part cross-sectional study in which high school girls completed a single 62-item survey. The main study (n = 95) and follow-up pilot expansion study (n = 75) were conducted at a private all-girls school and a public co-educational high school, respectively. Predictor variables included sources of vaccine information, vaccine-related knowledge (VRK), socio-demographic and attitudinal factors. Outcome variables were vaccination against the HPV and participation by the subject in decision-making about the vaccine. For the main study, a random sample of girls were selected, stratified by grade (25/grade). Questions were ordered and worded so as to avoid “stereotype threat” and other forms of bias and pilot tested.

Modern android robots have begun to penetrate the social realm of humans. This study quantitatively probed the impact of anthropomorphic robot appearance on human social interpretation of robot facial expression. The Uncanny Valley"theory describing the disturbing effect of imperfect human likenesses has been a dominant influence in discussions of human-robot social interaction, but measuring its effect on human social interactions with robots has been problematic. The present study addresses this issue by examining social responses of human participants to a series of digitally composed pictures of realistic robot faces that span a range from mechanical to human in appearance. Our first experiment provides evidence that an Uncanny Valley effect on social attractiveness is indeed a practical concern in the design of robots meant to interact socially with the lay public. In the second experiment, we employed game-theory research methods to measure the effect of subtle facial expressions in robots on human judgments of their trustworthiness as social counterparts. Our application of game-theory research methods to the study of human-robot interactions provides a model for such empirical measurement of human's social responses to android robots.

Stress dramatically exacerbates pain in diseases such as fibromyalgia and rheumatoid arthritis, but the underlying mechanisms are unknown. We tested the hypothesis that stress causes generalized hyperalgesia by enhancing pronociceptive effects of immune mediators. Rats exposed to nonhabituating sound stress exhibited no change in mechanical nociceptive threshold, but showed a marked increase in hyperalgesia evoked by local injections of prostaglandin E2 or epinephrine. This enhancement, which developed more than a week after exposure to stress, required concerted action of glucocorticoids and catecholamines at receptors located in the periphery on sensory afferents. The altered response to pronociceptive mediators involved a switch in coupling of their receptors from predominantly stimulatory to inhibitory G-proteins (Gs to Gi), and for prostaglandin E2, emergence of novel dependence on protein kinase Cε. Thus, an important mechanism in generalized pain syndromes may be stress-induced coactivation of the hypothalamo-pituitary-adrenal and sympathoadrenal axes, causing a long-lasting alteration in intracellular signaling pathways, enabling normally innocuous levels of immune mediators to produce chronic hyperalgesia.

The neurotoxic effects of catecholamine metabolites have been implicated in neurodegenerative diseases. As some sensory neurons express tyrosine hydroxylase and monoamine oxidase (MAO), we investigated the potential contribution of catecholamine metabolites to neuropathic pain in a model of alcoholic neuropathy. The presence of catecholamines in sensory neurons is supported by capsaicin‐stimulated epinephrine release, an effect enhanced in ethanol‐fed rats. mRNA for enzymes in dorsal root ganglia involved in catecholamine uptake and metabolism, dopamine β‐hydroxylase and MAO‐A, were decreased by neonatal administration of capsaicin. Ethanol‐induced hyperalgesia was attenuated by systemic and local peripheral administration of inhibitors of MAO‐A, reduction of norepinephrine transporter (NET) in sensory neurons and a NET inhibitor. Finally, intradermal injection of 3,4‐dihydroxyphenylglycolaldehyde (DOPEGAL), a neurotoxic MAO‐A catecholamine metabolite, produced robust mechanical hyperalgesia. These observations suggest that catecholamines in nociceptors are metabolized to neurotoxic products by MAO‐A, which can cause neuronal dysfunction underlying neuropathic pain.

Although the transient receptor potential vanilloid 4 (TRPV4) has been implicated in the process of osmomechanical transduction, it appears to make little contribution to the normal somatosensory detection of mechanical stimuli. However, evidence suggests that it may play an important role in mechanical hyperalgesia. In the present study, we examined the common requirement for TRPV4 in mechanical hyperalgesia associated with diverse pain models and investigated whether the very close association observed between TRPV4 and mechanical hyperalgesia, regardless of etiology, reflects a close functional connection of TRPV4 with other molecules implicated in mechanical transduction. In models of painful peripheral neuropathy associated with vincristine chemotherapy, alcoholism, diabetes, and human immunodeficiency virus/acquired immune deficiency syndrome therapy, mechanical hyperalgesia was markedly reduced by spinal intrathecal administration of oligodeoxynucleotides antisense to TRPV4. Similarly, mechanical hyperalgesia induced by paclitaxel, vincristine, or diabetes was strongly reduced in TRPV4 knock-out mice. We also show that α2β1 integrin and Src tyrosine kinase, which have been implicated in mechanical transduction, are important for the development of mechanical hyperalgesia, and that their contribution requires TRPV4. Furthermore, we establish a direct interaction between TRPV4, α2 integrin, and the Src tyrosine kinase Lyn in sensory neurons. We suggest that TRPV4 plays a role in mechanotransduction, as a component of a molecular complex that functions only in the setting of inflammation or nerve injury.