'One of the greatest injustices of our time': The impact of social representations of modern slavery in the UK-A mixed methods approach.

This study aimed to examine how social representations of modern slavery and immigration become entangled in newspaper media. 2672 UK newspaper articles were collated from 2013 to 2022 and analysed using Content Analysis (Descendant Hierarchical Classification) and Critical Discourse Analysis (CDA). Two themes and corresponding extracts were identified from the content analysis output and analysed using CDA allowing for the exploration of the role of the hegemonic social representations to understanding how discourses of modern slavery are reproduced through the othering in relation to ethnicity and migration.

GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents.

The NMDA receptor (NMDAR) antagonist ketamine has shown great potential as a rapid-acting antidepressant; however, its use is limited by poor oral bioavailability and a side effect profile that necessitates in-clinic dosing. GM-1020 is a novel NMDAR antagonist that was developed to address these limitations of ketamine as a treatment for depression. Here, we present the preclinical characterization of GM-1020 alongside ketamine, for comparison.

Understanding the evolution of trust in a participatory health research partnership: A qualitative study.

Introduction: Advancements in evaluating the impact of participatory health research (PHR) have been made through comprehensive models like the community-based participatory research (CBPR) conceptual model, which provides a useful framework for exploring how context and partnership processes can influence health research design and interventions. However, challenges in operationalising aspects of the model limit our understanding and evaluation of the PHR process. Trust is frequently identified as an important component of the CBPR model, which supports the development of key partnership outcomes, such as partnership synergy.

Long-term sea level rise modeling of a basin-tidal inlet system reveals sediment sinks.

Much of the world's population lives close to coastlines and this proximity is becoming increasingly impactful because of sea-level rise (SLR). Barrier islands and backbarrier saltmarshes, which comprise >10% of these coasts, are particularly susceptible. To better understand this risk, we model backbarrier morphologic and hydrodynamic evolution over a 200-year period of SLR, incorporating an erodible bed and a range of grain sizes.

A meta-analytical review of the impact of mindfulness on creativity: Framing current lines of research and defining moderator variables.

Findings relating to the impact of mindfulness interventions on creative performance remain inconsistent, perhaps because of discrepancies between study designs, including variability in the length of mindfulness interventions, the absence of control groups or the tendencies to explore creativity as one unitary construct. To derive a clearer understanding of the impact that mindfulness interventions may exert on creative performance, two meta-analytical reviews were conducted, drawing respectively on studies using a control group design (n = 20) and studies using a pretest-posttest design (n = 17). A positive effect was identified between mindfulness and creativity, both for control group designs (d = 0.

With equity in mind: Evaluating an interactive hybrid global surgery course for cross-site interdisciplinary learners.

There is limited understanding of the role of transcultural, cross-site educational partnerships for global surgery training between high- and low- or middle-income country (LMIC) institutions. We describe the development, delivery, and appraisal of a hybrid, synchronous, semester-long Global Surgical Care course by global health collaborators from widely different contexts, and evaluate the equity of the collaboration. The course was collaboratively modified by surgical educators and public health professionals with emphasis on collaboration ethics.

The public and patient involvement imperative in Ireland: Building on policy drivers.

What can we learn from the history of Public and Patient Involvement (PPI) in healthcare and research across global jurisdictions? Depending on region and context, the terminology and heritage of involvement in research vary. In this paper, we draw on global traditions to explore dominant themes and key considerations and critiques pertaining to PPI in order to inform a PPI culture shift in Ireland. We then describe the heritage of PPI in Ireland and present the case for combining methodological imperatives with policy drivers to support and encourage involvement.

First-in-Human Evaluation of F-PF-06445974, a PET Radioligand That Preferentially Labels Phosphodiesterase-4B.

Phosphodiesterase-4 (PDE4), which metabolizes the second messenger cyclic adenosine monophosphate (cAMP), has 4 isozymes: PDE4A, PDE4B, PDE4C, and PDE4D. PDE4B and PDE4D have the highest expression in the brain and may play a role in the pathophysiology and treatment of depression and dementia. This study evaluated the properties of the newly developed PDE4B-selective radioligand F-PF-06445974 in the brains of rodents, monkeys, and humans.

Translational Pharmacology of PRAX-944, a Novel T-Type Calcium Channel Blocker in Development for the Treatment of Essential Tremor.

Background: Essential tremor is the most common movement disorder with clear unmet need. Mounting evidence indicates tremor is caused by increased neuronal burst firing and oscillations in cerebello-thalamo-cortical circuitry and may be dependent on T-type calcium channel activity. T-type calcium channels regulate sigma band electroencephalogram (EEG) power during non-rapid eye movement sleep, representing a potential biomarker of channel activity.

The novel persistent sodium current inhibitor PRAX-562 has potent anticonvulsant activity with improved protective index relative to standard of care sodium channel blockers.

Objective: This study investigates the effects of PRAX-562 on sodium current (I ), intrinsic neuronal excitability, and protection from evoked seizures to determine whether a preferential persistent I inhibitor would exhibit improved preclinical efficacy and tolerability compared to two standard voltage-gated sodium channel (Na ) blockers.

Methods: Inhibition of I  was characterized using patch clamp analysis. The effect on intrinsic excitability was measured using evoked action potentials recorded from hippocampal CA1 pyramidal neurons in mouse brain slices.

Discovery of the First Orally Available, Selective K1.1 Inhibitor: and Activity of an Oxadiazole Series.

The gene encodes the sodium-activated potassium channel K1.1 (Slack, Slo2.2).

Effects of mangrove cover on coastal erosion during a hurricane in Texas, USA.

We tested the hypothesis that mangroves provide better coastal protection than salt marsh vegetation using 10 1,008-m plots in which we manipulated mangrove cover from 0 to 100%. Hurricane Harvey passed over the plots in 2017. Data from erosion stakes indicated up to 26 cm of vertical and 970 cm of horizontal erosion over 70 months in the plot with 0% mangrove cover, but relatively little erosion in other plots.

Building Resources in Caregivers: Feasibility of a Brief Writing Intervention to Increase Benefit Finding in Caregivers.

The Building Resources in Caregivers (BRiC) is a pilot feasibility trial that compared the effects of a 2-week benefit finding writing expressive intervention to a control intervention, who wrote about the weather. Caregivers completed primary (benefit finding) and secondary (quality of life, depression and anxiety) outcome measures at pre (t1), immediately post-test (t2) and 1 month later (t3). They also completed measures relating to trial feasibility, difficulty, and acceptance.

Helping parents to help children overcome fear: The influence of a short video tutorial.

Objectives: Anxiety runs in families, and its transmission is largely environmental. However, studies rarely explore this process in clinically anxious parents or ask participants to face a genuine fear. We also do not know whether this process is modifiable.

The location discrimination reversal task in mice is sensitive to deficits in performance caused by aging, pharmacological and other challenges.

Deficits in hippocampal-mediated pattern separation are one aspect of cognitive function affected in schizophrenia (SZ) or Alzheimer's disease (AD). To develop novel therapies, it is beneficial to explore this specific aspect of cognition preclinically. The location discrimination reversal (LDR) task is a hippocampal-dependent operant paradigm that evaluates spatial learning and cognitive flexibility using touchscreens.

Preventing family transmission of anxiety: Feasibility RCT of a brief intervention for parents.

Objectives: Children of anxious parents are at high risk of anxiety disorders themselves. The evidence suggests that this is due to environmental rather than genetic factors. However, we currently do little to reduce this risk of transmission.

Verbal working memory and functional large-scale networks in schizophrenia.

The aim of this study was to test whether bilinear and nonlinear effective connectivity (EC) measures of working memory fMRI data can differentiate between patients with schizophrenia (SZ) and healthy controls (HC). We applied bilinear and nonlinear Dynamic Causal Modeling (DCM) for the analysis of verbal working memory in 16 SZ and 21 HC. The connection strengths with nonlinear modulation between the dorsolateral prefrontal cortex (DLPFC) and the ventral tegmental area/substantia nigra (VTA/SN) were evaluated.

The Discovery of a Novel Phosphodiesterase (PDE) 4B-Preferring Radioligand for Positron Emission Tomography (PET) Imaging.

As part of our effort in identifying phosphodiesterase (PDE) 4B-preferring inhibitors for the treatment of central nervous system (CNS) disorders, we sought to identify a positron emission tomography (PET) ligand to enable target occupancy measurement in vivo. Through a systematic and cost-effective PET discovery process, involving expression level (B) and biodistribution determination, a PET-specific structure-activity relationship (SAR) effort, and specific binding assessment using a LC-MS/MS "cold tracer" method, we have identified 8 (PF-06445974) as a promising PET lead. Compound 8 has exquisite potency at PDE4B, good selectivity over PDE4D, excellent brain permeability, and a high level of specific binding in the "cold tracer" study.

The isozyme selective phosphodiesterase-4 inhibitor, ABI-4, attenuates the effects of lipopolysaccharide in human cells and rodent models of peripheral and CNS inflammation.

Inhibitors of phosphodiesterase-4 (PDE4) have been approved for the treatment of inflammatory disorders, but are associated with dose-limiting nausea and vomiting. These side effects are hypothesized to be mediated by inhibition of the PDE4D isozyme. Here we demonstrate the anti-inflammatory effects of the novel brain penetrant PDE4D-sparing PDE4 inhibitor, ABI-4.

Defining the brain circuits involved in psychiatric disorders: IMI-NEWMEDS.

Despite the vast amount of research on schizophrenia and depression in the past two decades, there have been few innovative drugs to treat these disorders. Precompetitive research collaborations between companies and academic groups can help tackle this innovation deficit, as illustrated by the achievements of the IMI-NEWMEDS consortium.

Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function.

Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions.

The effect of targeting tolerance of children's negative emotions among anxious parents of children with anxiety disorders: A pilot randomised controlled trial.

Following cognitive behavioural therapy for child anxiety a significant minority of children fail to lose their diagnosis status. One potential barrier is high parental anxiety. We designed a pilot RCT to test claims that parental intolerance of the child's negative emotions may impact treatment outcomes.

Substance misuse: can midwives really make a difference?

Substance misuse makes a woman vulnerable. During pregnancy, in particular, the issues surrounding Substance misuse and its treatment are very emotive. Pregnancy often prompts women who substance misuse to seek help for their addiction for the first time, but for some it is part of a cycle of failure and loss: failure at rehabilitation and facing the loss of yet another child, be it through child protection issues or from the medical complications of addiction.