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Investigating Neurometabolite Changes in Response to Median Nerve Stimulation
Get PDFBackground: Rhythmic median nerve stimulation (MNS) at 10Hz has been shown to cause a substantial reduction in tic frequency in individuals with Tourette syndrome. The mechanism of action is currently unknown but is hypothesized to involve entrainment of oscillations within the sensorimotor cortex. Objective: We used functional magnetic resonance spectroscopy (fMRS) to explore the dynamic effects of MNS on neurometabolite concentrations. Methods: Here, we investigated the effects of rhythmic and arrhythmic 10Hz MNS on glutamate (Glu) and GABA concentrations in the contralateral sensorimotor cortex in 15 healthy controls, using a blocked fMRS design. We used a Mescher–Garwood-semi-localized by adiabatic selective refocusing (MEGA-sLASER) sequence at 7 T. Results: Our results show no difference in the difference-from-baseline measures between the two stimulation conditions. Looking at the effect of MNS over both conditions there is a trend for an initial increase in Glu/tCr (total creatine) followed by a decrease over time, whereas GABA/tCr decreased during each stimulation block. Conclusions: These results suggest that despite entrainment of oscillations during rhythmic MNS, there are no significant differences in the tonic neuromodulatory effects of rhythmic and arrhythmic stimulation. The reduction in Glu over the course of stimulation may reflect a decrease in the glutamatergic firing due to adaptation. This may make it less likely that an involuntary movement is generated during continuous stimulation
Real-time monitoring procedures for early detection of bubbles
Get PDFAsset price bubbles and crashes can have severe consequences for the stability of financial and economic systems. Policymakers require timely identification of such bubbles in order to respond to their emergence. In this paper we propose new econometric procedures that improve the speed of detection for an emerging asset price bubble in real time. Our new monitoring procedures make use of alternative variance standardisations that are better able to capture the behaviour of the underlying process during a bubble phase. We derive asymptotic results to show that using these alternative variance standardisations does not increase the probability of false detection under the no-bubble (unit root) null hypothesis relative to existing procedures. However, Monte Carlo simulations demonstrate that much earlier detection becomes possible with our new procedures under the bubble (explosive autoregressive) alternative. Empirical applications to OECD housing markets and bitcoin prices show the value in terms of earlier detection of bubbles that our new procedures can achieve. In particular, we show that the United States housing bubble that preceded the global financial crisis could have been detected as early as 1999:Q1 by our new procedures
Chronic pancreatitis: a case ascertainment study
Get PDFBackground Chronic pancreatitis (CP) is a debilitating condition, characterised by chronic inflammation and fibrosis of the pancreas. The population frequency of CP is poorly understood. Therefore, we used a broad pragmatic approach to estimate the frequency of CP among a patient population undergoing investigations at a UK tertiary university hospital.Method All adult patients who, during 2006–2014, underwent abdominal CT MRI, abdominal X-ray, endoscopic ultrasonography (EUS), faecal elastase testing, received a pancreatin prescription or a recorded primary/comorbid ICD diagnosis of CP were screened (screening cohort) for inclusion. By applying the well-recognised CT, MRI and EUS criteria to the screening cohort, patients with CP were identified (study cohort). The incidence and point prevalence of CP were calculated, and changes in incidence were modelled using Poisson regression.Results Screening cohort included 24 271 cases, and 1003 patients who met the diagnostic criteria for CP were included in the study cohort. The median age of diagnosis was 65 (IQR 50–76); the majority were males (n=656, 65.4%) and of European ancestry (n=884, 88.1%). The annual incidence of diagnosis increased by a mean of 4.1% per year (95% CI 0.5% to 7.8%; p=0.03) over the study period ranging from 8.5 to 13.8 per 100 000 general population. The point prevalence also increased reaching 53.6 (95% CI 48.3 to 59.4) per 100 000 population at the end of the study period.Conclusion This study provides a clear method of pragmatically identifying patients with CP in a clinical setting. The incidence of CP diagnosis in patients undergoing investigations in hospital increased gradually in Greater Nottingham
The impact of life story work during peer worker training: Identity reconstruction, social connection, and recovery
No full textObjective: Personal recovery has become a guiding vision in mental health care, and peer workers play a key role in assisting individuals on their recovery journey. As a component of training to prepare for this role, peer workers need to engage with their own life story, in order to support recovery in both them and in the service users they will assist. The purpose of the present study was to explore the impact of life story work on peer workers. Method: Fifteen individuals training to be peer workers were interviewed to explore the impact of telling and listening to life stories. Reflexive thematic analysis involving two analysts was conducted. Results: Three main themes were identified: (a) life story work as identity reconstruction, (b) social connection through life story sharing, and (c) negative impacts of engaging with life stories in peer worker training. Each theme was connected to a number of subthemes. Conclusions and Implications for Practice: Life story work can both facilitate personal recovery in peer workers during their training and aid them in utilizing their stories in their future peer worker roles. Training needs to prepare peer workers to deal with the future role-related challenges of life story work
Implications of Large Language Models for Clinical Practice: Ethical Analysis Through the Principlism Framework
Get PDFIntroduction: The potential applications of large language models (LLMs)—a form of generative artificial intelligence (AI)—in medicine and health care are being increasingly explored by medical practitioners and health care researchers. Methods: This paper considers the ethical implications of LLMs for medical practitioners in their delivery of clinical care through the ethical framework of principlism. Findings: It finds that, regarding beneficence, LLMs can improve patient outcomes through supporting administrative tasks that surround patient care, and by directly informing clinical care. Simultaneously, LLMs can cause patient harm through various mechanisms, meaning non-maleficence would prevent their deployment in the absence of sufficient risk mitigation. Regarding autonomy, medical practitioners must inform patients if their medical care will be influenced by LLMs for their consent to be informed, and alternative care uninfluenced by LLMs must be available for patients who withhold such consent. Finally, regarding justice, LLMs could promote the standardisation of care within individual medical practitioners by mitigating any biases harboured by those practitioners and by protecting against human factors, while also up-skilling existing medical practitioners in low-resource settings to reduce global health disparities. Discussion: Accordingly, this paper finds a strong case for the incorporation of LLMs into clinical practice and, if their risk of patient harm is sufficiently mitigated, this incorporation might be ethically required, at least according to principlism
In vivo calcium imaging reveals directional sensitivity of C-low threshold mechanoreceptors
Get PDFC-low threshold mechanoreceptors (C-LTMRs) in animals (termed C-tactile (CT) fibres in humans) are a subgroup of C-fibre primary afferents, which innervate hairy skin and respond to low-threshold punctate indentations and brush stimuli. These afferents respond to gentle touch stimuli and are implicated in mediating pleasant/affective touch. These afferents have traditionally been studied using low-throughput, technically challenging approaches, including microneurography in humans and teased fibre electrophysiology in other mammals. Here we suggest a new approach to studying genetically labelled C-LTMRs using in vivo calcium imaging. We used an automated rotating brush stimulus and von Frey filaments, applied to the hairy skin of anaesthetized mice to mirror light and affective touch. Simultaneously we visualized changes in C-LTMR activity and confirmed that these neurons are sensitive to low-threshold punctate mechanical stimuli and brush stimuli with a strong preference for slow brushing speeds. We also reveal that C-LMTRs are directionally sensitive, showing more activity when brushed against the natural orientation of the hair. We present in vivo calcium imaging of genetically labelled C-LTMRs as a useful approach that can reveal new aspects of C-LTMR physiology
An indirect data-driven model-updating framework to estimate soil–pile interaction parameters using output-only data
Get PDFThis paper presents a data-driven model updating framework to estimate the operational parameters of a laterally-impacted pile. The goal is to facilitate the estimation of soil–pile interaction parameters such as the mobilized mass and stiffness, as well as geometrical data such as embedded pile length, using output-only information. Accurate knowledge of mass, stiffness, and pile embedded length is essential for understanding foundation behavior when developing digital-twin models of structures for the purpose of damage detection. The method first employs subspace identification to determine modal parameters and quantifies their uncertainties using output-only data. The covariance matrix adaptation evolution strategy (CMA-ES), a stochastic evolutionary algorithm, is subsequently used to update the model. The effectiveness of the approach is demonstrated through its application to numerical models in this paper, to quantify errors, and subsequently to data from a documented full-scale field test of a pile subjected to an impact load. The work underscores the potential of statistical updating in advancing the accuracy and reliability of soil–structure interaction parameter estimation for systems where only output data might exist
Elective peri-operative management of adults taking glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic peptide agonists andsodium-glucose cotransporter-2 inhibitors: a multidisciplinary consensus statement: A consensus statement from the Association of Anaesthetists, Association of BritishClinical Diabetologists, British Obesity and Metabolic Surgery Society, Centrefor Perioperative Care, Joint British Diabetes Societies for Inpatient Care, RoyalCollege of Anaesthetists, Society for Obesity and Bariatric Anaesthesia and UK Clinical Pharmacy Association
Get PDFIntroduction: Glucagon-like peptide-1 receptor agonists, dual glucose-dependent insulinotropic peptide receptor agonists and sodium-glucose cotransporter-2 inhibitors are used increasingly in patients receiving peri-operative care. These drugs may be associated with risks of peri-operative pulmonary aspiration or euglycaemic ketoacidosis. We produced a consensus statement for the peri-operative management of adults taking these drugs. Methods: This multidisciplinary consensus statement included surgeons, anaesthetists, physicians, pharmacists and people with lived experience relevant to these guidelines. Following the directed literature review, a three-round modified Delphi process was conducted to generate and ratify recommendations. Results: Patients taking glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic peptide receptor agonists should: continue these drugs before surgery; have full risk assessment and stratification; and receive peri-operative techniques that may mitigate risk of pulmonary aspiration before, during and after sedation or general anaesthesia. Patients taking sodium-glucose cotransporter-2 inhibitors should omit them the day before and the day of a procedure. All patients should have risks and mitigation strategies discussed with a shared decision-making approach. Discussion: Until more evidence becomes available, this pragmatic, multidisciplinary consensus statement aims to support shared decision-making and improve safety for patients taking glucagon-like peptide-1 receptor agonists, dual glucose-dependent insulinotropic peptide receptor agonists and sodium-glucose cotransporter-2 inhibitors during the peri-operative period
Where Do Children Look When Watching Videos With Same-Language Subtitles?
Get PDFInfluential campaigns in the United Kingdom and the United States have argued that same-language television subtitles may help children learn to read. In this study, we investigated the extent to which primary-school children pay attention to and read subtitles and whether this is related to their reading proficiency. We tracked the eye movements of 180 British children in Years 1 to 6 who watched videos with and without subtitles. Results showed that attention to subtitles was associated with reading proficiency: Superior readers were more likely to look at subtitles than less proficient readers and spent more time on them. When children looked at words in the subtitles, they showed evidence of reading them. We conclude that some degree of reading fluency may be necessary before children pay attention to subtitles. However, by the third or fourth year of reading instruction, most children read sufficiently quickly to follow same-language subtitles and potentially learn from them
Understanding the Molecular Interactions Between Influenza A Virus and Streptococcus Proteins in Co-Infection: A Scoping Review
Get PDFInfluenza A virus infections are known to predispose infected individuals to bacterial infections of the respiratory tract that result in co-infection with severe disease outcomes. Co-infections involving influenza A viruses and streptococcus bacteria result in protein–protein interactions that can alter disease outcomes, promoting bacterial colonisation, immune evasion, and tissue damage. Focusing on the synergistic effects of proteins from different pathogens during co-infection, this scoping review evaluated evidence for protein–protein interactions between influenza A virus proteins and streptococcus bacterial proteins. Of the 2366 studies initially identified, only 32 satisfied all the inclusion criteria. Analysis of the 32 studies showed that viral and bacterial neuraminidases (including NanA, NanB and NanC) are key players in desialylating host cell receptors, promoting bacterial adherence and colonisation of the respiratory tract. Virus hemagglutinin modulates bacterial virulence factors, hence aiding bacterial internalisation. Pneumococcal surface proteins (PspA and PspK), bacterial M protein, and pneumolysin (PLY) enhance immune evasion during influenza co-infections thus altering disease severity. This review highlights the importance of understanding the interaction of viral and bacterial proteins during influenza virus infection, which could provide opportunities to mitigate the severity of secondary bacterial infections through synergistic mechanisms
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