Several leading therapies for anxiety-related disorders rely on the principles of extinction learning. However, despite decades of development and research, many of these treatments remain only moderately effective. Developing techniques to improve extinction learning is an important step towards developing improved and mechanistically-informed exposure-based therapies.
View Article and Find Full Text PDFEvent boundaries help structure the content of episodic memories by segmenting continuous experiences into discrete events. Event boundaries may also serve to preserve meaningful information within an event, thereby actively separating important memories from interfering representations imposed by past and future events. Here, we tested the hypothesis that event boundaries organize emotional memory based on changing dynamics as events unfold.
View Article and Find Full Text PDFSafety learning involves associating stimuli with the absence of threats, enabling the inhibition of fear and anxiety. Despite growing interest in psychology, psychiatry, and neuroscience, safety learning lacks a formal consensus definition, leading to inconsistent methodologies and varied results. Conceptualized as a form of inhibitory learning (conditioned inhibition), safety learning can be understood through formal learning theories, such as the Rescorla-Wagner and Pearce-Hall models.
View Article and Find Full Text PDFWhile fear generalizes widely, extinction is stimulus-specific. Using a hybrid conditioning/episodic memory paradigm, subjects encoded nonrepeating category exemplars during fear conditioning and extinction. Twenty-four hours later, a surprise memory test included old, similar, and novel category exemplars.
View Article and Find Full Text PDFCatalysts can undergo structural changes during the reaction, affecting the number and/or the shape of active sites. For example, Rh can undergo interconversion between nanoparticles and single atoms when CO is present in the reaction mixture. Therefore, calculating a turnover frequency in such cases can be challenging as the number of active sites can change depending on the reaction conditions.
View Article and Find Full Text PDFSafety learning creates associations between conditional stimuli and the absence of threat. Studies of human fear conditioning have accumulated evidence for the neural signatures of safety over various paradigms, aligning on several common brain systems. While these systems are often interpreted as underlying safety learning in a generic sense, they may instead reflect the expression of learned safety, pertaining to processes of fear inhibition, positive affect, and memory.
View Article and Find Full Text PDFFear conditioning paradigms are critical to understanding anxiety-related disorders, but studies use an inconsistent array of methods to quantify the same underlying learning process. We previously demonstrated that selection of trials from different stages of experimental phases and inconsistent use of average compared to trial-by-trial analysis can deliver significantly divergent outcomes, regardless of whether the data is analysed with extinction as a single effect, as a learning process over the course of the experiment, or in relation to acquisition learning. Since small sample sizes are attributed as sources of poor replicability in psychological science, in this study we aimed to investigate if changes in sample size influences the divergences that occur when different kinds of fear conditioning analyses are used.
View Article and Find Full Text PDFSafety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviors. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task with ultra-high field (7 Tesla) fMRI to examine the neural basis of safety learning in 49 healthy participants.
View Article and Find Full Text PDFClin Endocrinol (Oxf)
March 2022
Obesity is becoming increasingly prevalent in paediatric populations worldwide. In addition to increasing prevalence, the severity of obesity is also continuing to rise. Taken together, these findings demonstrate a worrying trend and highlight one of the most significant challenges to public health.
View Article and Find Full Text PDFThe only licensed dengue vaccine, Dengvaxia, increases risk of severe dengue when given to individuals without prior dengue virus (DENV) infection but is protective against future disease in those with prior DENV immunity. The World Health Organization has recommended using rapid diagnostic tests (RDT) to determine history of prior DENV infection and suitability for vaccination. Dengue experts recommend that these assays be highly specific (≥98%) to avoid erroneously vaccinating individuals without prior DENV infection, as well as be sensitive enough (≥95%) to detect individuals with a single prior DENV infection.
View Article and Find Full Text PDFSafety learning occurs when an otherwise neutral stimulus comes to signal the absence of threat, allowing organisms to use safety information to inhibit fear and anxiety in nonthreatening environments. Although it continues to emerge as a topic of relevance in biological and clinical psychology, safety learning remains inconsistently defined and under-researched. Here, we analyse the Pavlovian conditioned inhibition paradigm and its application to the study of safety learning in humans.
View Article and Find Full Text PDFObjectives: Childhood obesity is a public health concern worldwide, with rates continuing to rise, despite preventive measures. Lifestyle modification remains the mainstay in the treatment of patients with excessive weight, but unfortunately, this is not always successful. Options for medical management of obesity in the paediatric population are limited.
View Article and Find Full Text PDFDeficient safety learning has been implicated in the pathogenesis of anxiety disorders. Despite increased translational interest, there has been limited research on the basis of safety learning in humans. Here, we examined safety learning in seventy-three healthy participants via a modified Pavlovian conditioned inhibition paradigm, featuring a conditioned threat stimulus that was reinforced alone (A+), but not when combined with a second stimulus (the conditioned inhibitor, AX-).
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
March 2021
There currently exist few frameworks for common neurobiology between reexperiencing and negative cognitions and mood symptoms of PTSD. Adopting a dopaminergic framework for PTSD unites many aspects of unique symptom clusters, and this approach also links PTSD symptomology to common comorbidities with a common neurobiological deficiency. Here we review the dopamine literature and incorporate it with a growing field of research that describes both the contribution of endocannabinoids to fear extinction and PTSD, as well as the interactions between dopaminergic and endocannabinoid systems underlying this disorder.
View Article and Find Full Text PDFRobustness of fear conditioning and extinction paradigms has become increasingly important for many researchers interested in improving the study of anxiety and trauma disorders. We recently illustrated the wide variability in data analysis techniques in this paradigm, which we argued may result in a lack of robustness. In the current study, we resampled data from six of our own fear acquisition and extinction data sets, with skin conductance as the outcome.
View Article and Find Full Text PDFActa Psychol (Amst)
February 2019
Anxiety disorders are characterised by the perception of fear and threat in the presence of stimuli that are neutral or ambiguous. Attempts in previous research to explain the relationship between anxiety and fear learning have been inconsistent, possibly due to the influence of an unmeasured mechanism that mediates the relationship between them. Working memory capacity has been suggested as one such mechanism.
View Article and Find Full Text PDFTo determine trends in the diagnostic distribution of esophageal motility disorders after implementation of the Chicago Classification Version 3.0 (CC V3.0) for interpretation of high-resolution manometry (HRM) studies compared to non-Chicago Classification criteria.
View Article and Find Full Text PDFBackground: Total joint replacement of the 1st metatarso-phalangeal Joint (MTPJ) has been controversial as arthrodesis remains a good option for patients with end stage 1st MTPJ arthritis. We present a multi centre service evaluation of the ROTO-glide device METHODS: 33 ROTO-glide procedures were carried out in 30 patients across 7 sites within the UK. Exclusion criteria - hallux valgus and arthritis, age below 45 years and over 80 years, inflammatory joint disease.
View Article and Find Full Text PDFEndoscopic bariatric therapies are predicted to become much more widely used in North America for obese patients who are not candidates for bariatric surgery. Of all the endoscopic bariatric therapies, intragastric balloons (IGBs) have the greatest amount of clinical experience and published data supporting their use. Three IGBs are FDA approved and are now commercially available in the USA (Orbera, ReShape Duo, and Obalon) with others likely soon to follow.
View Article and Find Full Text PDFBackground: Proximal osteotomy of the first metatarsal is often indicated for Hallux Valgus correction. Previously recognised complications however, include transfer metatarsalgia, first metatarsophalangeal joint stiffness, problems with fixation and prominence of metalware.
Methods: We report on one year follow up of an international prospective series between June 2009 and October 2012 involving three centres, including 91 feet (58 patients) that underwent proximal osteotomy, using a new locking plate applied to the plantar surface of the metatarsal.
It is unclear whether recombinant human growth hormone (rhGH) in inflammatory bowel disease (IBD) alters cytokine profile. The objective of this study is to evaluate changes in cytokines and systemic markers of the insulin growth factor axis following 6 months of rhGH treatment in children with IBD. In a six-month randomised control trial in children with IBD treated with rhGH at 0.
View Article and Find Full Text PDFOne of the causes of growth failure is growth hormone deficiency. The outcome of growth hormone therapy to treat this depends on a number of multifaceted issues, including the child, the family and the choice of medication device. Providing support and promoting adherence--key nurse roles--are essential for success
View Article and Find Full Text PDFClin Gastroenterol Hepatol
September 2013
Background & Aims: Most patients with hilar cholangiocarcinomas present with unresectable tumors, so only palliative biliary drainage with self-expanding metal stents (SEMS) is possible. Stents eventually cease to function because of tumor overgrowth and/or other causes, so it is important to identify factors that affect stent patency and failure. We examined the patency of endoscopically placed SEMS in patients with hilar cholangiocarcinoma and factors associated with patency.
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