Volunteering for Infection: Participant Perspectives on a Hepatitis C Virus Controlled Human Infection Model.

Ethical human subjects research requires participants to be treated safely and respectfully, yet much bioethical debate takes place without participants. We aim to address this gap in the context of controlled human infection model (CHIM) research. Based upon our own experience as study participants, and bolstered by a survey of 117 potential hepatitis C virus CHIM participants, we present ideas to inform efficient, ethical, and scientifically useful study design. We advocate for full protocol transparency, higher compensation, commitment to the rapid dissemination of study results, and proactive efforts to detail risk-minimization efforts as early as possible in the recruitment process, among other measures. We encourage researchers to proactively partner with volunteer advocacy organizations that promote collective representation of volunteers to maximize their agency, and guard against ethical issues arising from healthy human subjects research.

Prevent the Bleed: How Surgeons Can Lead the National Conversation About Firearm Safety Forward.

: In the 5 years since the Sandy Hook elementary school shooting that claimed the lives of 20 children and 6 of their teachers, we have witnessed intolerably more mass shooting events. In the intervening years, over 150,000 Americans have died because of firearm violence, 3 times the number who lost their lives during the Revolutionary war. In the last 2 months, we have been left reflecting on 2 more tragedies. The first came on October 1 in Las Vegas, at the Route 91 music festival where 58 were killed and over 500 injured by a single gunman. The second, on November 5, took place in Sutherland Springs, Texas (population 600) near San Antonio and claimed the lives of 26 men women and children while they prayed. As was witnessed in Orlando and San Bernardino, these most recent mass casualty incidents strained first responders, law enforcement, and the state's trauma systems to their breaking point.Once again, we were left searching for the reasons behind these tragedies asking predictable questions: who did this and why? Was it part of a terrorist plot or a lone psychopath with a grudge? Were the weapons obtained legally, and why would anyone need so many? How can we stop this from happening again?

Breaking boundaries: optimizing reconsolidation-based interventions for strong and old memories.

Recent research has demonstrated that consolidated memories can enter a temporary labile state after reactivation, requiring restabilization in order to persist. This process, known as reconsolidation, potentially allows for the modification and disruption of memory. Much interest in reconsolidation stems from the possibility that maladaptive memory traces-a core feature of several psychiatric conditions-could be tackled by disrupting their reconsolidation. However, research has indicated a range of supposed boundary conditions on the induction of reconsolidation. Stronger memories, often resulting from exposure to stressful conditions, or older memories, appear to be relatively resistant to undergoing reconsolidation. This may be taken as a potential stumbling block for reconsolidation-based interventions: in clinical practice, old and strong maladaptive memories are the norm rather than the exception. Yet, boundary conditions have been derived from limited experimental evidence, are not unique to reconsolidation-based interventions, and do not seem to be absolute. In this paper, we review a range of experimental studies that have aimed to disrupt old memories, or memories that were strengthened by stress manipulations, through reconsolidation. Such research highlights several techniques that could be used to optimize reconsolidation-based approaches and overcome putative boundary conditions. We supplement this review of experimental literature with a case study of a reconsolidation-based treatment of a strong and decades-old phobia for mice, further suggesting that age and strength of memory may not be insurmountable barriers. Translating findings from basic science, to human experiments, to clinical applications and back again, can potentially unlock powerful new treatments for the many people who suffer daily from anxiety disorders.

Tackling maladaptive memories through reconsolidation: From neural to clinical science.

Behavioral neuroscience has greatly informed how we understand the formation, persistence, and plasticity of memory. Research has demonstrated that memory reactivation can induce a labile period, during which previously consolidated memories are sensitive to change, and in need of restabilization. This process is known as reconsolidation. Such findings have advanced not only our basic understanding of memory processes, but also hint at the prospect of harnessing these insights for the development of a new generation of treatments for disorders of emotional memory. However, even in simple experimental models, the conditions for inducing memory reconsolidation are complex: memory labilization appears to result from the interplay of learning history, reactivation, and also individual differences, posing difficulties for the translation of basic experimental research into effective clinical interventions. In this paper, we review a selection of influential animal and human research on memory reconsolidation to illustrate key insights these studies afford. We then consider how these findings can inform the development of new treatment approaches, with a particular focus on the transition of memory from reactivation, to reconsolidation, to new memory formation, as well as highlighting possible limitations of experimental models. If the challenges of translational research can be overcome, and if reconsolidation-based procedures become a viable treatment option, then they would be one of the first mental health treatments to be directly derived from basic neuroscience research. This would surely be a triumph for the scientific study of mind and brain.

Trends in food and beverage television brand appearances viewed by children and adolescents from 2009 to 2014 in the USA.

OBJECTIVE: Public health experts raise concerns about marketing unhealthy products to young people through television (TV) product placements. Coca-Cola brand appearances (product placements) reached a substantial child and adolescent audience in 2008, but additional brands now sponsor popular programming. We aimed to quantify child and adolescent exposure to food and beverage appearances since 2008. DESIGN: In 2015, we purchased Nielsen data on occurrences and child/adolescent exposure to food, beverage and restaurant brand appearances on US prime-time TV from 2009 to 2014, and analysed appearances by product category, company, brand and year. We compared exposure to appearances with exposure to traditional commercials for top brands. SETTING: Nationally representative panel of approximately 20 000 TV-viewing households. SUBJECTS: Children (2-11 years) and adolescents (12-17 years). RESULTS: Exposure to food and beverage brand appearances peaked in 2012 and declined through 2014. Whereas full-calorie soda brands dominated before 2012, other sugary drink and quick-serve restaurant brands contributed over one-third of appearances viewed by children in 2013 and 2014. Nine hundred and fifty-four companies had brand appearances from 2009 to 2014, but just four were responsible for over half of exposures: The Coca-Cola Company, Dr Pepper Snapple Group, PepsiCo and Starbucks. Approximately half were viewed on reality TV programmes and one sitcom. Each year from 2009 to 2013, brand appearance exposure exceeded traditional advertising exposure for at least one brand. CONCLUSIONS: Despite recent reductions in brand appearances viewed by young people, some unhealthy branded products continue to be marketed via this method. We suggest policy options to reduce child and adolescent exposure to such appearances.

A paradigm shift in the treatment of emotional memory disorders: Lessons from basic science.

Experiments demonstrating post-reactivation amnesia for learned fear in animals have generated a novel and influential hypothesis on the plasticity of memory, usually referred to as memory reconsolidation. The clinical potential of pharmacologically disrupting the process of memory reconsolidation has sparked a wave of interest into whether this phenomenon can also be demonstrated in humans, and ultimately harnessed for therapeutic purposes. In this essay we outline how the work of Karim Nader and colleagues has moved the field forward from a focus on extinction learning to the prospect of disrupting memory reconsolidation. We then review some promising findings on the necessary conditions, as well as potential boundary conditions, of pharmacologically disrupting the process of memory reconsolidation obtained in our laboratory. Even though laboratory experiments in animals and humans suggest that we may be at the brink of a breakthrough in fundamentally changing emotional memories, the necessary and sufficient conditions for targeting and disrupting memory reconsolidation in clinical practice are largely unknown. There is likely no universally effective reactivation procedure for triggering the reconsolidation of clinically significant emotional memories, and the impact of subtle boundary conditions observed in basic experiments compounds this issue. Notwithstanding these challenges, the discovery of changing emotional memory through disrupting the process of memory reconsolidation has unquestionably invigorated the field.

Examining the Surgical Life.

Debriefing after a major event is a key component in ongoing improvement in performance. Likewise, reflecting on one's career at the time of leaving the operating room environment is an opportunity to transmit the lessons learned from decades of surgical practice. The authors, recently retired from daily operating and leaders in American surgery, reflect on the impact of surgical life on surgeons and their personal lives. Observations regarding selection of medical students, surgical trainees and practice models are presented from this perspective.

Placebo and Non-specific Effects in Reconsolidation-Based Treatment for Arachnophobia.

The idea that maladaptive memories may be rendered susceptible to interference after reactivation raises the possibility of reactivating and neutralizing clinically-relevant emotional memories. In this study, we sought to investigate the feasibility of such a "reconsolidation-based" intervention for arachnophobia, drawing upon previous research that successfully reduced fear of spiders in a subclinical sample. In Experiment 1, we piloted several reactivation procedures for conducting a reconsolidation-based treatment for arachnophobic individuals. All procedures involved some form of brief exposure to a fear-provoking spider, followed by the administration of 40 mg propranolol. In Experiment 2, we conducted a double-blind, placebo-controlled assessment of one procedure tested in Experiment 1. In Experiment 1, we found that most reactivation procedures produced drops in self-reported fear of spiders from pre- to post-treatment, including fear declines that were apparent up to 6- and even 14-months later. However, in Experiment 2, we found no evidence that the participants receiving propranolol were better off than those who received placebo. While our findings are limited by the small sample sizes used, they nevertheless show a different pattern of responses than was observed in a previous reconsolidation-based intervention for subclinical spider fearful participants. Alterations to the protocol made to accommodate the clinical participants may have led to greater opportunities for non-specific effects (e.g., exposure, placebo effects) to drive change in the participants. Our findings highlight both the challenges of translating reconsolidation-based procedures into clinical interventions, as well as the importance of controls for non-specific effects in reconsolidation-based research.

Expectations of objective threats and aversive feelings in specific fears.

Mistaken beliefs about danger posed by feared stimuli are considered a key factor causing and maintaining fears. Such beliefs are intriguing because many fearful people express them, but acknowledge they are untrue in reality. While previous research indicates fearful individuals may not wholly endorse their beliefs about objective threats (e.g., the spider will bite), expectations of negative subjective consequences (e.g., I will feel terrible) are also likely to be important. We investigated the extent to which participants' expectations of objective and subjective threats were sensitive to manipulations that encouraged them to consider whether their expectations were likely to happen in reality. Across five online experiments (N = 560, or 727 with more liberal inclusion criteria), such manipulations produced lower expectancy ratings for objective but not subjective threats (versus participants who gave ratings without the manipulation). Most participants reported that anticipation of negative feelings was more concerning than actual danger. Hence, numerous fear-relevant expectations about objective threat-considered central in understanding why people are irrationally afraid-respond to small cognitive manipulations. Additionally, expectations of negative subjective experiences during fear-provoking encounters appear to be more consistently endorsed, and feature prominently in fearful individuals' concerns about what will happen in a fear-relevant situation.

Encoding or consolidation? The effects of pre- and post-learning propranolol on the impact of an emotional scene.

BACKGROUND AND OBJECTIVES: Researchers have conceived of post-traumatic stress disorder (PTSD) as a disorder of memory, and proposed that blocking the impact of stress-related noradrenaline release in the aftermath of trauma may be a way of preventing the 'over-consolidation' of trauma-related memories. Experimental research in humans has been limited by typically focusing on declarative memory for emotional stories, and has mainly given propranolol before learning. In contrast, the clinical studies that we comprehensively review are hampered by practical challenges, such as reliably administering propranolol in a time window sufficiently close to the traumatic event. In this study, we aimed to assess the impact of both pre- and post-learning propranolol on emotional and declarative memory for an emotional scene, using the 'trauma film paradigm'. METHODS: To control for drug and timing effects, participants received a pill (40 mg propranolol or placebo) both 60 min before and within 5 min after viewing a 12 min, emotionally arousing trauma film, and were assigned to one of the three conditions: propranolol-placebo (n = 25), placebo-propranolol (n = 25), or placebo-placebo (n = 25). We assessed participants' immediate emotional responses to the scene, as well as delayed impact (intrusions, Impact of Events Scale) and declarative memory. RESULTS: Using Bayesian informative hypothesis testing, we found that pre-learning propranolol reduced the initial emotional impact of the 'trauma film'. However, we did not find strong evidence for an impact of pre- or post-learning propranolol on later consequences of having watched the emotional film (intrusions, Impact of Events, or tests of declarative memory). Exploratorily restricting analyses to women, we did find evidence suggesting that pre-encoding propranolol could reduce the rate of intrusions and self-reported negative impact of the emotional scene one week later. LIMITATIONS: Floor effects in the delayed impact of the emotional scene could preclude observing differences as a function of propranolol, and propranolol dosage may need to be increased. CONCLUSIONS: An impact of propranolol on encoding could raise difficulties in interpretation when only pre-encoding propranolol is used to make inferences about consolidation. We discuss the challenges of elucidating the mechanistic underpinnings of propranolol's reported effects on memory.

Reconsolidation-based treatment for fear of public speaking: a systematic pilot study using propranolol.

Pharmacological manipulation of memory reconsolidation opens up promising new avenues for anxiety disorder treatment. However, few studies have directly investigated reconsolidation-based approaches in subclinical or clinical populations, leaving optimal means of fear memory reactivation unknown. We conducted a systematic pilot study to assess whether a reconsolidation-based treatment could tackle public speaking anxiety in a subclinical sample (N = 60). As lab studies indicate that the duration of reactivation may be important for inducing reconsolidation, we investigated several speech lengths to help inform further translational efforts. Participants underwent a stress-inducing speech task composed of 3-min preparation, and from 0 to 9 min of public speaking, in 1-min increments. They then received either 40 mg of propranolol (n = 40) or placebo (n = 20), double-blind, allocated 4:2 for each speech duration. Participants performed a second speech 1 week post treatment, and were followed up with questionnaires 1- and 3 months later. Both self-reported speech distress and questionnaire measures of public speaking anxiety showed clear reductions following treatment. However, propranolol did not reliably outperform placebo, regardless of speech duration at treatment. Physiological responses (heart rate and salivary cortisol) to the public speaking task remained stable from treatment to test. These findings highlight the challenges facing the translation of laboratory research on memory reconsolidation into clinical interventions. Lack of explicit controls for factors beyond duration, such as 'prediction error', could explain these null findings, but positive results in clinical interventions are needed to demonstrate that taking such factors into account can deliver the promises of reconsolidation-based therapy.

Human memory reconsolidation: A guiding framework and critical review of the evidence.

Research in nonhuman animals suggests that reactivation can induce a transient, unstable state in a previously consolidated memory, during which the memory can be disrupted or modified, necessitating a process of restabilization in order to persist. Such findings have sparked a wave of interest into whether this phenomenon, known as reconsolidation, occurs in humans. Translating research from animal models to human experiments and even to clinical interventions is an exciting prospect, but amid this excitement, relatively little work has critically evaluated and synthesized existing research regarding human memory reconsolidation. In this review, we formalize a framework for evaluating and designing studies aiming to demonstrate human memory reconsolidation. We use this framework to shed light on reconsolidation-based research in human procedural memory, aversive and appetitive memory, and declarative memory, covering a diverse selection of the most prominent examples of this research, including studies of memory updating, retrieval-extinction procedures, and pharmacological interventions such as propranolol. Across different types of memory and procedure, there is a wealth of observations consistent with reconsolidation. Moreover, some experimental findings are already being translated into clinically relevant interventions. However, there are a number of inconsistent findings, and the presence of alternative explanations means that we cannot conclusively infer the presence of reconsolidation at the neurobiological level from current evidence. Reconsolidation remains a viable but hotly contested explanation for some observed changes in memory expression in both humans and animals. Developing effective and efficient new reconsolidation-based treatments can be a goal that unites researchers and guides future experiments. (PsycINFO Database Record

Survey of American College of Surgeons Committee on trauma members on firearm injury: Consensus and opportunities.

BACKGROUND: In the United States, there is a perceived divide regarding the benefits and risks of firearm ownership. The American College of Surgeons Committee on Trauma Injury Prevention and Control Committee designed a survey to evaluate Committee on Trauma (COT) member attitudes about firearm ownership, freedom, responsibility, physician-patient freedom and policy, with the objective of using survey results to inform firearm injury prevention policy development. METHODS: A 32-question survey was sent to 254 current U.S. COT members by email using Qualtrics. SPSS was used for χ exact tests and nonparametric tests, with statistical significance being less than 0.05. RESULTS: Our response rate was 93%, 43% of COT members have firearm(s) in their home, 88% believe that the American College of Surgeons should give the highest or a high priority to reducing firearm-related injuries, 86% believe health care professionals should be allowed to counsel patients on firearms safety, 94% support federal funding for firearms injury prevention research. The COT participants were asked to provide their opinion on the American College of Surgeons initiating advocacy efforts and there was 90% or greater agreement on 7 of 15 and 80% or greater on 10 of 15 initiatives. CONCLUSION: The COT surgeons agree on: (1) the importance of formally addressing firearm injury prevention, (2) allowing federal funds to support research on firearms injury prevention, (3) retaining the ability of health care professionals to counsel patients on firearms-related injury prevention, and (4) the majority of policy initiatives targeted to reduce interpersonal violence and firearm injury. It is incumbent on trauma and injury prevention organizations to leverage these consensus-based results to initiate prevention, advocacy, and other efforts to decrease firearms injury and death. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level I; therapeutic care, level II.

Relationships Between Impulsivity, Anxiety, and Risk-Taking and the Neural Correlates of Attention in Adolescents.

Although impulsivity, anxiety, and risk-taking may relate to attentional processes, little research has directly investigated how each may be associated with specific facets of attentional processes and their underlying neural correlates. Nineteen adolescents performed a functional magnetic resonance imaging task involving simple, selective, and divided attention. Out-of-scanner-assessed impulsivity, anxiety, and risk-taking scores were not correlated with each other and showed task-phase-specific patterns of association. Results are discussed in light of research and theory suggesting a relationship between these domains and attention and may serve to focus future research aiming to understand these relationships.

Childhood trauma and neural responses to personalized stress, favorite-food and neutral-relaxing cues in adolescents.

Previous studies have found childhood trauma to be associated with functional and structural abnormalities in corticostriatal-limbic brain regions, which may explain the associations between trauma and negative mental and physical health outcomes. However, functional neuroimaging of maltreatment-related trauma has been limited by largely using generic and predominantly aversive stimuli. Personalized stress, favorite-food, and neutral/relaxing cues during functional magnetic resonance imaging were used to probe the neural correlates of emotional/motivational states in adolescents with varying exposure to maltreatment-related trauma. Sixty-four adolescents were stratified into high- or low-trauma-exposed groups. Cue-related measures of subjective anxiety and craving were collected. Relative to the low-trauma-exposed group, high-trauma-exposed adolescents displayed an increased activation of insula, anterior cingulate, and prefrontal cortex in response to stress cues. Activation in subcortical structures, including the hippocampus, was inversely correlated with subjective anxiety in the high- but not the low-trauma-exposed group. The high-trauma-exposed group displayed hypoactivity of cerebellar regions in response to neutral/relaxing cues. No group differences were observed in response to favorite-food cues. The relationship between trauma exposure and altered cortico-limbic circuitry may in part explain the association between childhood trauma and heightened vulnerability to emotional disturbances and risky behaviour. This may be particularly pertinent during adolescence when such difficulties often emerge. Further work is needed to elucidate the mechanism linking trauma to obesity.

Initial experience with single-incision laparoscopic cholecystectomy.

BACKGROUND: Single-incision laparoscopic surgery is now increasingly used as an approach for cholecystectomy, based on anecdotal reports of decreased pain, reduced need for hospitalization, and a better cosmetic result. This is a report of a single surgeon's (JKE) initial experience with single-incision laparoscopic cholecystectomy (SILC). STUDY DESIGN: We collected concurrent data on 238 consecutive patients undergoing SILC by 1 surgeon in a community hospital over 12 months. RESULTS: From June 2008 to June 2009, 238 consecutive patients underwent an attempted SILC for biliary colic or dyskinesia (75%) or acute cholecystitis (25%) by a single surgeon. Conversion to a standard laparoscopic cholecystectomy was necessary in 6 patients (2.5%) for inflammation or bleeding (n = 4) or short cystic duct (n = 2). Conversion to an open cholecystectomy was necessary in 1 patient (0.42%) for a short cystic duct. No injuries to the common bile duct occurred, the average operative time was 40 minutes, and 95% of patients (n = 226) were discharged home on the day of operation. Postoperative port site hematomas occurred in 3 patients (1.3%), and dehiscence of the umbilical skin incision in 2 (0.8%). No perioperative deaths occurred. CONCLUSIONS: This initial experience with SILC documents that the results of the procedure are equivalent to those with the standard procedure using 4 widely-spaced ports when performed by an experienced laparoscopic surgeon. Randomized trials will be necessary to document the suggested benefits of decreased pain and shorter hospitalization.