James cavanagh

BACKGROUND: Breast cancer results in a 3-4 fold increased risk of venous thromboembolism (VTE) which is associated with reduced patient survival. Despite this, the mechanisms underpinning breast cancer-associated thrombosis remain poorly defined. Tumour cells can trigger endothelial cell (EC) activation resulting in increased von Willebrand Factor (VWF) secretion. Importantly, elevated plasma VWF levels constitute an independent biomarker for VTE risk. Moreover, in a model of melanoma, treatment with low molecular weight heparin (LMWH) negatively regulated VWF secretion and attenuated tumour metastasis...

Antimicrobial resistance (AMR), particularly antibiotic resistance, is one of the most challenging global health threats of our time. Tackling AMR requires a multidisciplinary approach. Whether a clinical team member is a cleaner, nurse, doctor, pharmacist, or other type of health worker, their contribution towards keeping patients safe from infection is crucial to saving lives. Existing literature portrays that games can be a good way to engage communities in joint learning. This manuscript describes an educational antimicrobial stewardship (AMS) game that was co-created by a multidisciplinary team of health professionals spanning across high- and low- to middle-income countries...

BACKGROUND: Delirium is an important risk factor for subsequent dementia. However, the field lacks large studies with long-term follow-up of delirium in subjects initially free of dementia to clearly establish clinical trajectories. METHODS: We undertook a retrospective cohort study of all patients over the age of 65 diagnosed with an episode of delirium who were initially dementia free at onset of delirium within National Health Service Greater Glasgow & Clyde between 1996 and 2020 using the Safe Haven database...

The bench-to-bedside development of pro-cognitive therapeutics for psychiatric disorders has been mired by translational failures. This is, in part, due to the absence of pharmacologically sensitive cognitive biomarkers common to humans and rodents. Here, we describe a cross-species translational marker of reward processing that is sensitive to the aminergic agonist, d-amphetamine. Motivated by human electroencephalographic (EEG) findings, we recently reported that frontal midline delta-band power is an electrophysiological biomarker of reward surprise in humans and in mice...

The poor translatability between preclinical and clinical drug trials has limited pro-cognitive therapeutic development. Future pro-cognitive drug trials should use translatable cross-species cognitive tasks with biomarkers (1) relevant to specific cognitive constructs, and (2) sensitive to drug treatment. Here, we used a difficulty-modulated variant of a cross-species cognitive control task with simultaneous electroencephalography (EEG) to identify neurophysiological biomarkers sensitive to the pro-cognitive effects of dextroamphetamine (d-amp) (10 or 20 mg) in healthy adults (n = 23), in a randomized, placebo-controlled, counterbalanced, double blind, within-subject study, conducted across three test days each separated by one week...

PURPOSE: To quantify total daily energy expenditure (TEE) of international adult female soccer players. METHODS: Twenty-four professional players were studied during a twelve-day period where they participated in an international training camp (also inclusive of two competitive games) representing the English national team. TEE was assessed via the doubly labelled water (DLW) method during the full 12 days as well as the initial 4-day period prior to game one. Energy intake (EI) was also assessed (via weighed food analysis) during the initial 4-day period to permit estimation of energy availability (EA)...

When an object casts a shadow on a background surface, both the offset of the shadow and the blur of its penumbra are potential cues to the distance between the object and the background. However, the shadow offset and blur are also affected by the direction and angular extent of the light source and these are often unknown. This means that the observer must make some assumptions about the illumination, the expected distribution of depth, or the relation between offset and depth in order to use shadows to make distance judgments...

A common feature across neuropsychiatric disorders is inability to discontinue an action or thought once it has become detrimental. Reversal learning, a hallmark of executive control, requires plasticity within cortical, striatal and limbic circuits and is highly sensitive to disruption of N-methyl-d-aspartate receptor (NMDAR) function. In particular, selective deletion or antagonism of GluN2B containing NMDARs in cortical regions including the orbitofrontal cortex (OFC), promotes maladaptive perseveration...

The EEG feature known as the Reward Positivity (RewP) is elicited by reward receipt and appears to reflect sensitively and specifically positive prediction errors during reinforcement learning. Yet, the RewP also is modulated by state and trait affect, suggesting that it has a more complex computational role than simple reinforcement surprise. We conducted a series of experiments aimed to investigate underlying affect processing reflected in the RewP during a reinforcement learning task. In the first experiment (N = 25), we manipulated the type of rewards a person could win (simple points or hedonically-appraised pictures)...

There has been a fundamental failure to translate preclinically supported research into clinically efficacious treatments for psychiatric disorders. One of the greatest impediments toward improving this species gap has been the difficulty of identifying translatable neurophysiological signals that are related to specific behavioral constructs. Here, we present evidence from three paradigms that were completed by humans and mice using analogous procedures, with each task eliciting candidate a priori defined electrophysiological signals underlying effortful motivation, reinforcement learning, and cognitive control...

Background: The humeral head osteotomy during shoulder arthroplasty influences humeral component height, version and possibly neck-shaft angle. These parameters all potentially influence outcomes of anatomic and reverse shoulder replacement to a variable degree. Patient-specific guides and navigation have been studied and utilized clinically for glenoid component placement. Little, however, has been done to evaluate these techniques for humeral head osteotomies. The purpose of this study, therefore, was to evaluate the use of patient-specific guides and surgical navigation for executing a planned humeral head osteotomy...

BACKGROUND: Prior work suggests that event-related potential (ERP) studies in infancy may help predict developmental outcome. METHODS: As part of a longitudinal study of early child development, we used the auditory oddball stimulus paradigm with a portable electroencephalography system to obtain ERP data from two-month-old infants (32 term, six preterm) in Sri Lanka. The mismatch negativity was calculated between 200 and 350 milliseconds after stimulus presentation...

INTRODUCTION: The perinatal-postnatal family environment is associated with childhood outcomes including impacts on physical and mental health and educational attainment. Family longitudinal cohort studies collect in-depth data that can capture the influence of an era on family lifestyle, mental health, chronic disease, education and financial stability to enable identification of gaps in society and provide the evidence for changes in government in policy and practice. METHODS AND ANALYSIS: The Queensland Family Cohort (QFC) is a prospective, observational, longitudinal study that will recruit 12 500 pregnant families across the state of Queensland (QLD), Australia and intends to follow-up families and children for three decades...

We investigated spectral resting-state EEG in persons with chronic stroke-induced aphasia to determine its reliability, sensitivity, and relationship to functional behaviors. Resting-state EEG has not yet been characterized in this population and was selected given the demonstrated potential of resting-state investigations using other neuroimaging techniques to guide clinical decision-making. Controls and persons with chronic stroke-induced aphasia completed two EEG recording sessions, separated by approximately 1 month, as well as behavioral assessments of language, sensorimotor, and cognitive domains...

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining which patients do or do not develop apathy post-TBI. Here we aimed to elucidate the impact of TBI on motivational neural circuits, and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging (rsfMRI) data were collected in patients with subacute mild TBI (N=44), chronic mild-to-moderate TBI (N=26), and non-brain-injured control participants (CTRL; N=28)...

BACKGROUND: The objective was to determine the incidence of, and factors associated with contralateral neck failure (CNF) in oral tongue squamous cell carcinoma (OTSCC). METHODS: Consecutive patients with OTSCC between 2007 and 2016 were included. The predefined policy of the contralateral neck included neck dissection (ND) where the primary tumor extended/crossed midline or the contralateral neck was involved; and elective nodal irradiation (ENI) where the primary tumor was ≤1 cm from midline/2 cm from tip...

OBJECTIVES: Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses. METHODS: In a cohort of 341 delivering HIV- and HIV+ mother from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P...

Deficits in behavioral flexibility are a hallmark of multiple psychiatric, neurological, and substance use disorders. These deficits are often marked by decreased function of the prefrontal cortex (PFC); however, the genesis of such executive deficits remains understudied. Here we report how the most preventable cause of developmental disability, in utero exposure to alcohol, alters cortico-striatal circuit activity leading to impairments in behavioral flexibility in adulthood. We utilized a translational touch-screen task coupled with in vivo electrophysiology in adult mice to examine single unit and coordinated activity of the lateral orbital frontal cortex (OFC) and dorsolateral striatum (DS) during flexible behavior...

Patients with Parkinson's disease (PD) can have significant cognitive dysfunction; however, the mechanisms for these cognitive symptoms are unknown. Here, we used scalp electroencephalography (EEG) to investigate the cortical basis for PD-related cognitive impairments during interval timing, which requires participants to estimate temporal intervals of several seconds. Time estimation is an ideal task demand for investigating cognition in PD because it is simple, requires medial frontal cortical areas, and recruits basic executive processes such as working memory and attention...

The RTS,S/AS01E vaccine has shown consistent but partial vaccine efficacy in a pediatric phase 3 clinical trial using a 3-dose immunization schedule. A fourth-dose 18 months after the primary vaccination was shown to restore the waning efficacy. However, only total IgG against the immunodominant malaria vaccine epitope has been analyzed following the booster. To better characterize the magnitude, nature, and longevity of the immune response to the booster, we measured levels of total IgM, IgG, and IgG1-4 subclasses against three constructs of the circumsporozoite protein (CSP) and the hepatitis B surface antigen (HBsAg, also present in RTS,S) by quantitative suspension array technology in 50 subjects in the phase 3 trial in Manhiça, Mozambique...