Insular and prelimbic cortices control behavioral accuracy and precision in a temporal decision-making task in rats.

The anterior insular cortex (AIC) comprises a region of sensory integration. It appears to detect salient events in order to guide goal-directed behavior, code tracking errors, and estimate the passage of time. Temporal processing in the AIC may be instantiated by the integration of representations of interoception. Projections between the AIC and the medial prefrontal cortex (mPFC) - found both in rats and humans - also suggest a possible role for these structures in the integration of autonomic responses during ongoing behavior. Few studies, however, have investigated the role of AIC and mPFC in decision-making and time estimation tasks. Moreover, their findings are not consistent, so the relationship between temporal decision-making and those areas remains unclear. The present study employed bilateral inactivations to explore the role of AIC and prelimbic cortex (PL) in rats during a temporal decision-making task. In this task, two levers are available simultaneously (but only one is active), one predicting reinforcement after a short, and the other after a long-fixed interval. Optimal performance requires a switch from the short to the long lever after the short-fixed interval elapsed and no reinforcement was delivered. Switch behavior from the short to the long lever was dependent on AIC and PL. During AIC inactivation, switch latencies became more variable, while during PL inactivation switch latencies became both more variable and less accurate. These findings point to a dissociation between AIC and PL in temporal decision-making, suggesting that the AIC is important for temporal precision, and PL is important for both temporal accuracy and precision.

Early weight gain as a predictor of weight restoration in avoidant/restrictive food intake disorder.

BACKGROUND: Previous research has demonstrated that early weight gain in family-based treatment (FBT) is predictive of remission for adolescents with anorexia nervosa (AN). However, no published data has addressed if early weight gain is also predictive of reaching weight restoration (i.e., 95% EBW) in patients with avoidant/restrictive food intake disorder (ARFID). Furthermore, no studies have evaluated the performance of the statistical models used to predict weight restoration at the end of treatment. This study sought to examine whether early weight gain in ARFID is predictive of weight restoration at 20 weeks using ROC analysis. Additionally, this study assessed how accurately the model classified patients and what types of misclassifications occurred. METHODS: Participants (n = 130, 57.7% cisgender female 70.0% white) received virtual outpatient FBT. Receiver operating characteristics (ROC) were used to predict successful weight restoration at end of treatment, using early weight gain as the predictor. Twenty weeks was considered as the end of treatment, to align with the definition of end of treatment in FBT clinical trials. ROC analyses demonstrated that gaining at least 6.2 pounds by week 5 of treatment was the strongest predictor of achieving 95% EBW at 20 weeks (AUC = 0.72 [0.63, 0.81]). ROC analyses misclassified 35% of patients; the most common misclassification was predicting that a patient would not achieve 95% EBW when they actually did (61.6%). A logistical regression model, which included the patients' %EBW at admission in addition to early weight gain as a predictor, outperformed the ROC analyses (AUC = 0.90 [0.85, 0.95]) and provided additional context by showing the probability that a patient would succeed. CONCLUSION: Taken together, research demonstrates that early weight gain is a useful predictor of 95% EBW at 20 weeks of treatment for patients with ARFID who require weight restoration. Furthermore, results suggest that statistical models need to take into account additional information, such as %EBW at admission, along with early weight gain in order to more accurately predict which patients will reach weight restoration at week 20.

Results from this study indicate that when patients with avoidant/restrictive food intake disorder (ARFID) gain weight steadily at the beginning of treatment, it helps them reach 95% expected body weight (EBW) by week 20 of treatment. The more weight the patients gain each week early on, the better their chances of getting to 95% EBW by week 20. However, there are two important things to consider: how much the patients weigh when they start treatment (starting %EBW) and how much weight they gain each week. Both of these factors affect the chances of reaching 95% EBW by week 20. Thus, this study highlights the goals for gaining weight at the start of treatment need to be different for each person, depending on how much they weigh when they begin. This may help patients with ARFID reach the goal of being at 95% EBW within 20 weeks.

Eating Disorder Clinical Presentation and Treatment Outcomes by Gender Identity Among Children, Adolescents, and Young Adults.

PURPOSE: Current eating disorder treatment approaches for youth were developed for use with cisgender girls, which limits the understanding of effectiveness for cisgender boys and transgender and gender expansive (TGE) youth. Here, we compare treatment outcomes for cisgender boys and TGE youth with cisgender girls receiving family-based treatment for an eating disorder. METHODS: Patients were aged 6-24 and either active in treatment or discharged from September 1, 2020, to November 1, 2022 (N = 1,235). Patient exposure to treatment varied given individualized length of treatment. Outcomes include eating disorder symptoms, depression, anxiety, suicidality, caregiver burden, and parental confidence in supervising treatment. Treatment outcomes for cisgender boys and TGE youth were compared with cisgender girls. RESULTS: Patients included n = 975 cisgender girls, n = 152 cisgender boys, and n = 108 TGE youth. Anorexia nervosa was the most common diagnosis. Cisgender boys reported significantly lower eating disorder (b = -2.7 [-4.1, -1.3]), anxiety (b = -1.6 [-2.2, -0.9]), and depression (b = -1.7 [-2.4, -0.9]) symptoms at admission compared with cisgender girls. TGE patients had significantly higher anxiety (b = 1.08 [0.28, 1.91]) and depression (b = 1.72 [0.78, 2.65]) symptoms compared with cisgender girls. Cisgender boys started with significantly lower suicidal ideation (b = -1.28 [-2.19, -0.43]) and TGE patients with significantly higher suicidal ideation (b = 1.63 [0.76, 2.51]) than cisgender girls. All symptoms improved during treatment and improved at similar rates over time in treatment regardless of gender identity. DISCUSSION: Early evidence from this study supports the use of family-based treatment for cisgender boys and TGE youth with eating disorders. Further research is needed on the long-term outcomes of this approach for youth of all genders.

CD4+ T cell immunity against cutaneous melanoma encompasses multifaceted MHC II-dependent responses.

Whereas CD4+ T cells conventionally mediate antitumor immunity by providing help to CD8+ T cells, recent clinical studies have implied an important role for cytotoxic CD4+ T cells in cancer immunity. Using an orthotopic melanoma model, we provide a detailed account of antitumoral CD4+ T cell responses and their regulation by major histocompatibility complex class II (MHC II) in the skin. Intravital imaging revealed prominent interactions of CD4+ T cells with tumor debris-laden MHC II+ host antigen-presenting cells that accumulated around tumor cell nests, although direct recognition of MHC II+ melanoma cells alone could also promote CD4+ T cell control. CD4+ T cells stably suppressed or eradicated tumors even in the absence of other lymphocytes by using tumor necrosis factor-α and Fas ligand (FasL) but not perforin-mediated cytotoxicity. Interferon-γ was critical for protection, acting both directly on melanoma cells and via induction of nitric oxide synthase in myeloid cells. Our results illustrate multifaceted and context-specific aspects of MHC II-dependent CD4+ T cell immunity against cutaneous melanoma, emphasizing modulation of this axis as a potential avenue for immunotherapies.

The timing database: An open-access, live repository for interval timing studies.

Interval timing refers to the ability to perceive and remember intervals in the seconds to minutes range. Our contemporary understanding of interval timing is derived from relatively small-scale, isolated studies that investigate a limited range of intervals with a small sample size, usually based on a single task. Consequently, the conclusions drawn from individual studies are not readily generalizable to other tasks, conditions, and task parameters. The current paper presents a live database that presents raw data from interval timing studies (currently composed of 68 datasets from eight different tasks incorporating various interval and temporal order judgments) with an online graphical user interface to easily select, compile, and download the data organized in a standard format. The Timing Database aims to promote and cultivate key and novel analyses of our timing ability by making published and future datasets accessible as open-source resources for the entire research community. In the current paper, we showcase the use of the database by testing various core ideas based on data compiled across studies (i.e., temporal accuracy, scalar property, location of the point of subjective equality, malleability of timing precision). The Timing Database will serve as the repository for interval timing studies through the submission of new datasets.

The assessment of caregiver self-efficacy in a virtual eating disorder setting.

BACKGROUND: Caregiver self-efficacy is thought to be a key component for successful family-based treatment (FBT) for individuals with eating disorders. As such, interventions aimed at enhancing caregiver self-efficacy, often measured via the Parents Versus Anorexia scale, have been a focal point of FBT literature. However, studies looking at the relationship between caregiver self-efficacy and treatment outcomes have been mixed. We aimed to better understand the influence of caregiver self-efficacy on eating disorder treatment outcomes during FBT. METHODS: Caregiver self-efficacy was measured using the Parents Versus Eating Disorders (PVED) scale, an adapted version of the Parents Versus Anorexia scale, in a sample of 1051 patients with an eating disorder and 1528 caregivers (patients can have more than one caregiver) receiving virtual FBT. Across two multilevel models, we tested how caregiver self-efficacy changed over time and its association with changes in eating disorder symptoms and weight over the first 16 weeks of treatment. RESULTS: Over treatment, PVED scores increased (b = 0.79, SE = 0.04, CI [0.72, 0.86]) and starting PVED scores were predictive of improved eating disorder symptoms (b = - 0.73, SE = 0.22, CI [- 1.15, - 0.30]), but not weight (b = - 0.96, SE = 0.59, CI [- 2.10, 0.19]). We also found that PVED change-from-baseline scores were predictive of weight (b = - 0.48, SE = 0.03, CI [- 0.53, - 0.43]) such that patient weight was lower when caregiver reports of PVED were higher. Likewise, the association between caregiver change in PVED scores and weight varied as a function of treatment time (b = 0.27, SE = 0.01, CI [0.24, 0.29]). Results were consistent when isolating patients with anorexia nervosa. CONCLUSIONS: Caregiver self-efficacy during FBT improved over time but was not robustly associated with treatment outcomes. This may, in part, be due to psychometric properties of the PVED scale. We describe these issues and illustrate the need for development of a new measure of self-efficacy for caregivers supporting their loved ones through eating disorder treatment.

In family-based treatment (FBT) for eating disorders, caregivers play a central role in helping their child recover. Specifically, a caregiver's self-efficacy, or their confidence in their ability to cope with the challenges their child faces during treatment, is believed to be a key to successful treatment outcomes. However, research on the impact caregiver self-efficacy has on patient treatment outcomes is mixed. Using the Parent vs. Eating Disorder (PVED) scale, we looked at the association between caregiver self-efficacy and eating disorder symptoms and weight changes over time in a sample of 1051 patients receiving virtual FBT. Caregiver self-efficacy had little to no significant impact on treatment outcomes. We offer explanations about why our findings challenge existing research that supports the association between caregiver self-efficacy and outcomes. Namely, the PVED scale appears to measure caregiver perceptions of their role in the treatment process (and not self-efficacy). We believe a new measurement tool must be developed and tested for the field to move forward in its understanding of the role caregiver self-efficacy plays in FBT.

Food insecurity among youth seeking eating disorder treatment.

Food Insecurity (FI) is associated with a myriad of mental health concerns in children and adolescents. Eating disorder (ED) risk is higher in youth experiencing FI, and FI in childhood is associated with ED diagnoses later in life. Although a growing body of research has shown that FI is associated with a heightened risk for ED-related symptoms, little is known about how experiencing FI may impact ED treatment, particularly in youth. In this study, we characterize the treatment characteristics of youth aged 6-24 (N = 729) with FI receiving family-based treatment for an ED. FI was defined as self-reported experience of FI (family-level FI) at treatment admission, and living in a low income, low access area according to USDA census tract data. Seventeen patients (2.3 % of sample) self-reported family-level FI at intake and 24 (3.3 % of sample) were designated as living in a low income/low access location. Descriptive analyses only were used to characterize the sample due to sample sizes. Group means on measures of weight, ED symptomatology, depression, anxiety, and caregiver burden were evaluated at admission and after four, eight, 12, 16, and 20 weeks of treatment. Results characterize how FI may impact ED treatment and showcase variation in changes. ED treatment must be responsive to needs related to FI as access to and consumption of food is the very foundation of ED treatment.

Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer.

CD8+ tumor-infiltrating lymphocytes with a tissue-resident memory T (TRM) cell phenotype are associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, the relative contribution of CD8+ TRM cells to anti-tumor immunity and immune checkpoint blockade efficacy in breast cancer remains unknown. Here, we show that intratumoral CD8+ T cells in murine mammary tumors transcriptionally resemble those from TNBC patients. Phenotypic and transcriptional studies established two intratumoral sub-populations: one more enriched in markers of terminal exhaustion (TEX-like) and the other with a bona fide resident phenotype (TRM-like). Treatment with anti-PD-1 and anti-CTLA-4 therapy resulted in expansion of these intratumoral populations, with the TRM-like subset displaying significantly enhanced cytotoxic capacity. TRM-like CD8+ T cells could also provide local immune protection against tumor rechallenge and a TRM gene signature extracted from tumor-free tissue was significantly associated with improved clinical outcomes in TNBC patients treated with checkpoint inhibitors.

Elevations in End-Tidal CO 2 With CO 2 Use During Pediatric Endoscopy With Airway Protection: Is This Physiologically Significant?

BACKGROUND: Inflation of the gastrointestinal lumen is vital for proper visualization during endoscopy. Air, insufflated via the endoscope, is gradually being replaced with carbon dioxide (CO 2 ) in many centers, with the intention of minimizing post-procedural discomfort due to retained gas. Recent studies suggest that the use of CO 2 during pediatric esophagogastroduodenoscopy (EGD) with an unprotected airway is associated with transient elevations in exhaled CO 2 (end-tidal CO 2 , EtCO 2 ), raising safety concerns. One possible explanation for these events is eructation of insufflation gas from the stomach. OBJECTIVES: To distinguish eructated versus absorbed CO 2 by sampling EtCO 2 from a protected airway with either laryngeal mask airway (LMA) or endotracheal tube (ETT), and to observe for changes in minute ventilation (MV) to exclude hypoventilation events. METHODS: Double-blinded, randomized clinical trial of CO 2 versus air insufflation for EGD with airway protection by either LMA or ETT. Tidal volume, respiratory rate, MV, and EtCO 2 were automatically recorded every minute. Cohort demographics were described with descriptive characteristics. Variables including the percent of children with peak, transient EtCO 2 ≥ 60 mmHg were compared between groups. RESULTS: One hundred ninety-five patients were enrolled for 200 procedures. Transient elevations in EtCO 2 of ≥60 mmHg were more common in the CO 2 group, compared to the air group (16% vs 5%, P = 0.02), but were mostly observed with LMA and less with ETT. Post-procedure pain was not different between groups, but flatulence was reported more with air insufflation ( P = 0.004). CONCLUSION: Transient elevations in EtCO 2 occur more often with CO 2 than with air insufflation during pediatric EGD despite protecting the airway with an LMA or, to a lesser degree, with ETT. These elevations were not associated with changes in MV. Although no adverse clinical effects from CO 2 absorption were observed, these findings suggest that caution should be exercised when considering the use of CO 2 insufflation, especially since the observed benefits of using this gas were minimal.

Effectiveness of delivering evidence-based eating disorder treatment via telemedicine for children, adolescents, and youth.

Barriers limit access to eating disorder treatment. Evidence-based treatment delivered using telemedicine could expand access. This study determined the effectiveness of enhanced Family-Based Treatment (FBT+) delivered using telemedicine for children and adolescents with eating disorders. Participants had a confirmed eating disorder diagnosis, lived in states where treatment was available, and lived with a family member willing to participate. Virtual FBT+ was administered by a five-person team including a therapist, dietitian, medical provider, peer mentor, and family mentor for up to 12 months. Measures were recorded at baseline and varying frequencies throughout treatment. Weight was self-reported. Eating disorder symptoms were assessed with the Eating Disorder Examination-Questionnaire Short Form (EDE-QS) and depression and anxiety were measured using the Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7). Caregiver burden and self-efficacy were measured using the Burden Assessment Scale, and Parent Versus Eating Disorder scale. The majority of patients (N = 210; 6 to 24 years old [mean 16 · 1 years]) were cisgender female (83%) White, (71%), required weight restoration (78%), and had anorexia nervosa, restricting type (63%). After 16 weeks, patients on weight restoration gained on average 11 · 3 [9 · 86, 12 · 8] pounds and the average change in EDE-QS score was -6 · 31 [-8 · 67, -4 · 10] points. Similar reductions were seen for depression (-2 · 62 [-4 · 24, -1 · 04]), anxiety (-1 · 44 [-1 · 12, 0 · 78]), and caregiver burden (-4 · 41 [2 · 45, 6 · 31]). Caregiver self-efficacy increased by 4 · 56 [3 · 53, 5 · 61] points. Patients and caregivers reported satisfaction with treatment. Virtual FBT+ for eating disorders can transcend geographical and psychosocial treatment barriers, expanding access to evidence-based eating disorder treatment.

Evaluating differences in setting expected body weight for children and adolescents in eating disorder treatment.

OBJECTIVE: Weight restoration or weight gain is a common goal in eating disorder treatment. However, approaches to determine expected body weight (EBW) vary. A standardized approach based on normative data for a patient's age and gender uses weight associated with median BMI (mBMI). An individualized approach predicts EBW based on a patient's individual growth trajectory. Little research has examined differences in these approaches. METHOD: Weight and clinical data were collected from patients ages 6-20 enrolled in virtual eating disorder treatment. EBW associated with mBMI was compared with EBW using the individualized approach. Linear mixed effects models examined differences in weight, eating disorder symptoms, depression, and anxiety, and whether EBW approach varied by patient characteristics. RESULTS: Patients (N = 609) were on average age 15.6 (2.29), 85% were cisgender female, and predominantly diagnosed with anorexia nervosa (83.1%). The individualized approach led to significantly higher EBW on average (mean difference = 8.4 lbs [SE: .75]; p < .001) compared to mBMI; 70% of patients had a higher EBW using the individualized approach. Notably, EBW varied based on gender and diagnosis and it took longer on average to achieve individualized EBW. Time was the strongest predictor of changes in psychosocial outcomes and there were no significant differences by EBW approach. DISCUSSION: Results from this study indicate that an individualized approach led to significantly higher EBWs compared with using mBMI. As underestimation of EBW may lead to higher risk of relapse, eating disorder professionals should consider using an individualized approach for setting EBW. PUBLIC SIGNIFICANCE: For eating disorder patients who need to gain weight, accurately estimating target body weight for eating disorder treatment is critical to recovery and preventing relapse. An individualized, patient-centered approach to estimating target body weight more accurately estimated target body weight than the standardized, median body mass index approach. Using an individualized approach to treatment may improve a patient's likelihood of full recovery.

Recurrent Gastrointestinal Bleed Due to Small Bowel Vascular Malformation in a Patient with Turner Syndrome Diagnosed with Surgically Assisted Push Enteroscopy.

BACKGROUND Obscure gastrointestinal bleeding accounts for approximately 5% of all cases of gastrointestinal bleeding and the most frequent site is the small bowel. Turner syndrome (TS) is a genetic disorder of the second X chromosome in females. The association between gastrointestinal vascular malformations and Turner syndrome has been described in some case reports. Vascular malformation in Turner's syndrome can vary from asymptomatic to severe recurrent GI bleeds, but data on diagnosis and management of these patients are lacking. CASE REPORT A 14-year-old girl with TS presented with recurrent symptomatic melena. The initial work-up included a negative upper endoscopy, negative bidirectional endoscopies, and a video capsule endoscopy (VCE) that demonstrated large amount of blood and small erythematous lesion in the small bowel without active bleeding, and a negative Meckel scan. CT angiography was remarkable for prominent left lower mesenteric blood vessels, and a single-balloon enteroscopy demonstrated prominent vasculature throughout the small bowel. A a clip was placed at the site of a questionable bleed. The patient underwent a surgically assisted push enteroscopy due to recurrent bleeding; findings were consistent with diffuse vascular malformations. She was started on tranexamic acid and later transitioned to estrogen therapy without further reports of GI bleeding, anemia, or adverse effects from treatment 6 months after initial presentation. CONCLUSIONS Small bowel bleeding can be life-threating, and evidence-based guidelines in children are needed. Turner syndrome is associated with gastrointestinal vascular malformations, and suspicion for this diagnosis should be high for these patients when presenting with gastrointestinal bleeding. Estrogen might be an effective therapy in TS adolescent patients in the setting of diffuse vascular malformations (DVM).

Balancing the scale.

Traditional discussions involving 'basic' and 'applied' behavioral research often focus on the differences, or gaps, between these areas. They take place in different environments, use different methods, ask different questions, and have different objectives. Applied animal behavior is no exception. Focusing on the differences in these areas is to the detriment of a cohesive and complete understanding of animal behavior. This paper instead focuses on the similarities between these two sides, and presents them as a matter of scale. A series of real-life examples experienced by the authors is used to highlight how the skills and knowledge of both the applied and the basic sides are valuable and necessary to not only further both fields independently, but to develop a comprehensive understanding of animal behavior.

Problematic social media use is associated with the evaluation of both risk and ambiguity during decision making.

BACKGROUND AND AIMS: People can engage in excessive, maladaptive use of social media platforms. This problematic social media use mirrors substance use disorders with regard to symptoms and certain behavioral situations. For example, individuals with substance use disorders demonstrate aberrations in risk evaluations during decision making, and initial research on problematic social media use has revealed similar findings. However, these results concerning problematic social media use have been clouded by tasks that involve learning and that lack a clear demarcation between risky and ambiguous decision making. Therefore, we set out to specifically determine the relationship between problematic social media use and decision making under both risk and ambiguity, in the absence of learning. METHODS: We assessed each participant's (N = 90) self-reported level of problematic social media use. We then had them perform the wheel of fortune task, which has participants make choices between a sure option or either a risky or ambiguous gamble. In this way, the task isolates decisions made under risk and ambiguity, and avoids trial-to-trial learning. Results: We found that the greater an individual's problematic social media use, the more often that individual choses high-risk gambles or ambiguous gambles, regardless of the degree of ambiguity. DISCUSSION AND CONCLUSIONS: Our findings indicate that greater problematic social media use is related to a greater affinity for high-risk situations and overall ambiguity. These findings have implications for the field, specifically clarifying and extending the extant literature, as well as providing future avenues for research.

Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8+ T cells in skin.

Tissue-resident memory T cells (TRM cells) are key elements of tissue immunity. Here, we investigated the role of the regulator of T cell receptor and cytokine signaling, Ptpn2, in the formation and function of TRM cells in skin. Ptpn2-deficient CD8+ T cells displayed a marked defect in generating CD69+ CD103+ TRM cells in response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by a reduction in the proportion of KLRG1- memory precursor cells and a transcriptional bias toward terminal differentiation. Of note, forced expression of KLRG1 was sufficient to impede TRM cell formation. Normalizing memory precursor frequencies by transferring equal numbers of KLRG1- cells restored TRM generation, demonstrating that Ptpn2 impacted skin seeding with precursors rather than downstream TRM cell differentiation. Importantly, Ptpn2-deficient TRM cells augmented skin autoimmunity but also afforded superior protection from HSV-1 infection. Our results emphasize that KLRG1 repression is required for optimal TRM cell formation in skin and reveal an important role of Ptpn2 in regulating TRM cell functionality.

Problematic social media use is associated with increased risk-aversion after negative outcomes in the Balloon Analogue Risk Task.

Around the world, people display maladaptive, problematic use of online social networking sites (SNSs), like Facebook, Snapchat, and Instagram. The symptoms of this problematic SNS use are similar to symptoms of substance use and behavioral addictive disorders, such as relapse when attempting to quit. Individuals with substance use and behavioral addictive disorders also display increased risk-taking when making decisions, but little research has investigated decision making with respect to problematic SNS use. We therefore assessed risky decision making and problematic SNS use by utilizing the Balloon Analogue Risk Task (BART). In line with previous research on behavioral addictive disorders, we hypothesized that greater problematic SNS use would be linked with greater risk-taking. To address our hypothesis, we conducted three studies in which we administered the Bergen Social Media Addiction Scale to assess problematic SNS use and related scores to BART performance. Collectively, and counter to our initial hypothesis, we found a negative association between problematic SNS use and risk-taking. Specifically, the more problematic one's SNS use, the less risk they took, but this risk aversion only occurred after receiving negative feedback on previous decisions and then encountering a situation with less actual risk. Implications of this novel finding are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Peak Interval Procedure in Rodents: A Tool for Studying the Neurobiological Basis of Interval Timing and Its Alterations in Models of Human Disease.

Animals keep track of time intervals in the seconds to minutes range with, on average, high accuracy but substantial trial-to-trial variability. The ability to detect the statistical signatures of such timing behavior is an indispensable feature of a good and theoretically-tractable testing procedure. A widely used interval timing procedure is the peak interval (PI) procedure, where animals learn to anticipate rewards that become available after a fixed delay. After learning, they cluster their responses around that reward-availability time. The in-depth analysis of such timed anticipatory responses leads to the understanding of an internal timing mechanism, that is, the processing dynamics and systematic biases of the brain's clock. This protocol explains in detail how the PI procedure can be implemented in rodents, from training through testing to analysis. We showcase both trial-by-trial and trial-averaged analytical methods as a window into these internal processes. This protocol has the advantages of capturing timing behavior in its full-complexity in a fashion that allows for a theoretical treatment of the data.

The importance of migratory connectivity for global ocean policy.

The distributions of migratory species in the ocean span local, national and international jurisdictions. Across these ecologically interconnected regions, migratory marine species interact with anthropogenic stressors throughout their lives. Migratory connectivity, the geographical linking of individuals and populations throughout their migratory cycles, influences how spatial and temporal dynamics of stressors affect migratory animals and scale up to influence population abundance, distribution and species persistence. Population declines of many migratory marine species have led to calls for connectivity knowledge, especially insights from animal tracking studies, to be more systematically and synthetically incorporated into decision-making. Inclusion of migratory connectivity in the design of conservation and management measures is critical to ensure they are appropriate for the level of risk associated with various degrees of connectivity. Three mechanisms exist to incorporate migratory connectivity into international marine policy which guides conservation implementation: site-selection criteria, network design criteria and policy recommendations. Here, we review the concept of migratory connectivity and its use in international policy, and describe the Migratory Connectivity in the Ocean system, a migratory connectivity evidence-base for the ocean. We propose that without such collaboration focused on migratory connectivity, efforts to effectively conserve these critical species across jurisdictions will have limited effect.

Bayesian Behavioral Systems Theory.

Behavioral Systems Theory suggests that observable behavior is embedded in a hierarchy. A CS elicits behavior because, after learning, it activates a pathway through this hierarchy. Much of Timberlake's body of work on Behavioral Systems Theory focuses on the conditions that support the conditioning of these pathways. Most notably, his work shows that the identity of the CS, US, and the CS-US interval all help support conditioning of the system. Here, we use recent experiments in the interval timing literature to motivate a Bayesian implementation of Behavioral Systems Theory. There is a probability distribution over possible pathways through the hierarchy, and the one that maximizes reinforcement is elicited. This probability distribution is conditioned on background information, like the CS-US interval and the animal's motivational state. Lower level actions of the hierarchy, like tracking prey, are conditioned on higher level goals, like the general search for food. Our implementation of Behavioral Systems Theory captures the essential features of Timberlake's verbal model; it acts as a glue, integrating sensory, timing, and decision mechanisms with observed behavior.

CD8+ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver.

Liver tissue-resident memory T (Trm) cells migrate throughout the sinusoids and are capable of protecting against malaria sporozoite challenge. To gain an understanding of liver Trm cell development, we examined various conditions for their formation. Although liver Trm cells were found in naive mice, their presence was dictated by antigen specificity and required IL-15. Liver Trm cells also formed after adoptive transfer of in vitro-activated but not naive CD8+ T cells, indicating that activation was essential but that antigen presentation within the liver was not obligatory. These Trm cells patrolled the liver sinusoids with a half-life of 36 days and occupied a large niche that could be added to sequentially without effect on subsequent Trm cell cohorts. Together, our findings indicate that liver Trm cells form as a normal consequence of CD8+ T cell activation during essentially any infection but that inflammatory and antigenic signals preferentially tailor their development.