Search

Inclusion body myositis (IBM) is an inflammatory myopathy, characterised by slow progression of weakness, skeletal muscle atrophy, and heterogeneous clinical presentation. This variability in disease progression and presentation complicates tracking of clinical progress and intervention response in clinical trials, presenting challenges in identifying reliable outcome measures. We aimed to identify the most useful suite of clinician-assessed and patient-reported outcome measures (PROMs) for use in clinical practice and trials from a selection of the most commonly used outcome measures in IBM. We retrospectively analysed clinician-assessed outcome measures (manual muscle testing (MMT8, MMT12)), right- and left-handed grip strength, modified timed up and go (mTUG), two-minute walk test (2MWT); a clinician-administered patient-reported tool (IBM Functional Rating Scale (IBMFRS)); and PROMs including the eating assessment tool (EAT-10), and neuromuscular symptom score (NSS) from 20 participants attending a single specialist myositis clinic in Perth, Australia. Correlation analysis revealed significant correlations between the IBMFRS, MMT8, MMT12, mTUG and 2MWT (p < 0.05). The NSS strongly correlated with the MMT8, MMT12 and 2MWT (p < 0.05). Univariate regression analyses revealed that 2MWT, MMT12 and mTUG were significant predictors of the IBMFRS and NSS, and backward stepwise linear regression highlighted that the 2MWT was a significant positive predictor for the IBMFRS (p < 0.001). Overall, we concluded that the IBMFRS, NSS, 2MWT and mTUG models were the best predictors of patient-perceived physical function in IBM., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose of Review: This review offers a contemporary clinical approach to the recognition, prevention and management of sarcopenia, and discusses recent clinically relevant advances in the aetiopathogenesis of muscle ageing that may lead to future therapeutic targets., Recent Findings: The key recent directions for sarcopenia are in the diagnosis, understanding molecular mechanisms and management. Regarding the recognition of the condition, it has become increasingly clear that different definitions hamper progress in understanding. Therefore, the Global Leadership in Sarcopenia has been established in 2022 to develop a universally accepted definition. Moreover, substantial work is occurring to understand the various roles and contribution of inflammation, oxidative stress, mitochondrial dysfunction and metabolic dysregulation on skeletal muscle function and ageing. Finally, the role of resistance-based exercise regimes has been continually emphasised. However, the role of protein supplementation and hormone replacement therapy (HRT) are still under debate, and current clinical trials are underway., Summary: With the global ageing of our population, there is increasing emphasis on maintaining good health. Maintenance of skeletal muscle strength and function are key to preventing frailty, morbidity and death., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Atrial and ventricular fibrillation (AF/VF) are characterized by the repetitive regeneration of topological defects known as phase singularities (PSs). The effect of PS interactions has not been previously studied in human AF and VF. We hypothesized that PS population size would influence the rate of PS formation and destruction in human AF and VF, due to increased inter-defect interaction. PS population statistics were studied in computational simulations (Aliev-Panfilov), human AF and human VF. The influence of inter-PS interactions was evaluated by comparison between directly modeled discrete-time Markov chain (DTMC) transition matrices of the PS population changes, and M/M/∞ birth-death transition matrices of PS dynamics, which assumes that PS formations and destructions are effectively statistically independent events. Across all systems examined, PS population changes differed from those expected with M/M/∞. In human AF and VF, the formation rates decreased slightly with PS population when modeled with the DTMC, compared with the static formation rate expected through M/M/∞, suggesting new formations were being inhibited. In human AF and VF, the destruction rates increased with PS population for both models, with the DTMC rate increase exceeding the M/M/∞ estimates, indicating that PS were being destroyed faster as the PS population grew. In human AF and VF, the change in PS formation and destruction rates as the population increased differed between the two models. This indicates that the presence of additional PS influenced the likelihood of new PS formation and destruction, consistent with the notion of self-inhibitory inter-PS interactions., (© 2023 Crown.)

Background and Objective: Renewal theory is a statistical approach to model the formation and destruction of phase singularities (PS), which occur at the pivots of spiral waves. A common issue arising during observation of renewal processes is an inspection paradox, due to oversampling of longer events. The objective of this study was to characterise the effect of a potential inspection paradox on the perception of PS lifetimes in cardiac fibrillation. Methods: A multisystem, multi-modality study was performed, examining computational simulations (Aliev-Panfilov (APV) model, Courtmanche-Nattel model), experimentally acquired optical mapping Atrial and Ventricular Fibrillation (AF/VF) data, and clinically acquired human AF and VF. Distributions of all PS lifetimes across full epochs of AF, VF, or computational simulations, were compared with distributions formed from lifetimes of PS existing at 10,000 simulated commencement timepoints. Results: In all systems, an inspection paradox led towards oversampling of PS with longer lifetimes. In APV computational simulations there was a mean PS lifetime shift of +84.9% (95% CI, ± 0.3%) ( p < 0.001 for observed vs overall), in Courtmanche-Nattel simulations of AF +692.9% (95% CI, ±57.7%) ( p < 0.001), in optically mapped rat AF +374.6% (95% CI, ± 88.5%) ( p = 0.052), in human AF mapped with basket catheters +129.2% (95% CI, ±4.1%) ( p < 0.05), human AF-HD grid catheters 150.8% (95% CI, ± 9.0%) ( p < 0.001), in optically mapped rat VF +171.3% (95% CI, ±15.6%) ( p < 0.001), in human epicardial VF 153.5% (95% CI, ±15.7%) ( p < 0.001). Conclusion: Visual inspection of phase movies has the potential to systematically oversample longer lasting PS, due to an inspection paradox. An inspection paradox is minimised by consideration of the overall distribution of PS lifetimes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jenkins, Dharmaprani, Schopp, Quah, Tiver, Mitchell, Xiong, Aguilar, Pope, Akar, Roney, Niederer, Nattel, Nash, Clayton and Ganesan.)

During the ongoing COVID-19 pandemic, PCR testing and antigen tests have proven critical for helping to stem the spread of its causative agent, SARS-CoV-2. However, these methods suffer from either general applicability and/or sensitivity. Moreover, the emergence of variant strains creates the need for flexibility to correctly and efficiently diagnose the presence of substrains. To address these needs we developed the diagnostic test ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) Optimization) which employs Cas13 to diagnose patients in 1 h without sophisticated equipment. Using an extensive panel of clinical samples, we demonstrate that ADESSO correctly identifies infected individuals at a sensitivity and specificity comparable to RT-qPCR on extracted RNA and higher than antigen tests for unextracted samples. Altogether, ADESSO is a fast, sensitive and cheap method that can be applied in a point of care setting to diagnose COVID-19 and can be quickly adjusted to detect new variants., (© 2022. The Author(s).)

The mechanisms governing cardiac fibrillation remain unclear; however, it most likely represents a form of spatiotemporal chaos with conservative system dynamics. Renewal theory has recently been suggested as a statistical formulation with governing equations to quantify the formation and destruction of wavelets and rotors in fibrillatory dynamics. In this perspective Review, we aim to explain the origin of the renewal theory paradigm in spatiotemporal chaos. The ergodic nature of pattern formation in spatiotemporal chaos is demonstrated through the use of three chaotic systems: two classical systems and a simulation of cardiac fibrillation. The logistic map and the baker's transformation are used to demonstrate how the apparently random appearance of patterns in classical chaotic systems has macroscopic parameters that are predictable in a statistical sense. We demonstrate that the renewal theory approach developed for cardiac fibrillation statistically predicts pattern formation in these classical chaotic systems. Renewal theory provides governing equations to describe the apparently random formation and destruction of wavelets and rotors in atrial fibrillation (AF) and ventricular fibrillation (VF). This statistical framework for fibrillatory dynamics provides a holistic understanding of observed rotor and wavelet dynamics and is of conceptual significance in informing the clinical and mechanistic research of the rotor and multiple-wavelet mechanisms of AF and VF.

Background: Atrial fibrillation (AF) is characterized by the repetitive regeneration of unstable rotational events, the pivot of which are known as phase singularities (PSs). The spatial concentration and distribution of PSs have not been systematically investigated using quantitative statistical approaches., Objectives: We utilized a geospatial statistical approach to determine the presence of local spatial concentration and global clustering of PSs in biatrial human AF recordings., Methods: 64-electrode conventional basket (~5 min, n = 18 patients, persistent AF) recordings were studied. Phase maps were produced using a Hilbert-transform based approach. PSs were characterized spatially using the following approaches: (i) local "hotspots" of high phase singularity (PS) concentration using Getis-Ord Gi* ( Z  ≥ 1.96, P  ≤ .05) and (ii) global spatial clustering using Moran's I (inverse distance matrix)., Results: Episodes of AF were analyzed from basket catheter recordings (H: 41 epochs, 120 000 s, n = 18 patients). The Getis-Ord Gi* statistic showed local PS hotspots in 12/41 basket recordings. As a metric of spatial clustering, Moran's I showed an overall mean of 0.033 (95% CI: 0.0003-0.065), consistent with the notion of complete spatial randomness., Conclusion: Using a systematic, quantitative geospatial statistical approach, evidence for the existence of spatial concentrations ("hotspots") of PSs were detectable in human AF, along with evidence of spatial clustering. Geospatial statistical approaches offer a new approach to map and ablate PS clusters using substrate-based approaches., Competing Interests: Authors declare no conflict of interests for this article., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Unstable functional reentrant circuits known as rotors have been consistently observed in atrial fibrillation and are mechanistically believed critical to the maintenance of the arrhythmia. Recently, using a Poisson renewal theory-based quantitative framework, we have demonstrated that rotor formation (λ f ) and destruction rates (λ d ) can be measured using in vivo electrophysiologic data. However, the association of λ f and λ d with clinical, electrical, and structural markers of atrial fibrillation phenotype is unknown., Methods: RENEWAL-AF is a multicenter prospective cross-sectional study recruiting adult patients with paroxysmal or persistent atrial fibrillation undergoing clinically indicated catheter ablation. Patients will undergo intraprocedural electrophysiologic atrial fibrillation mapping, with λ f and λ d to be determined from 2-minute unipolar electrogram recordings acquired before ablation. The primary objective will be to determine the association of λ f and λ d as markers of fibrillatory dynamics with clinical, electrical, and structural markers of atrial fibrillation clinical phenotype, measured by preablation transthoracic echocardiogram and cardiac magnetic resonance imaging. An exploratory objective is the noninvasive assessment of λ f and λ d using surface ECG characteristics via a machine learning approach., Results: Not applicable., Conclusion: This pilot study will provide insight into the correlation between λ f /λ d with clinical, electrophysiological, and structural markers of atrial fibrillation phenotype and provide a foundation for the development of noninvasive assessment of λ f /λ d using surface ECG characteristics will help expand the use of λ f /λ d in clinical practice., Competing Interests: Authors declare no conflict of interests for this article, (© 2020 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Background: Despite a century of research, no clear quantitative framework exists to model the fundamental processes responsible for the continuous formation and destruction of phase singularities (PS) in cardiac fibrillation. We hypothesized PS formation/destruction in fibrillation could be modeled as self-regenerating Poisson renewal processes, producing exponential distributions of interevent times governed by constant rate parameters defined by the prevailing properties of each system., Methods: PS formation/destruction were studied in 5 systems: (1) human persistent atrial fibrillation (n=20), (2) tachypaced sheep atrial fibrillation (n=5), (3) rat atrial fibrillation (n=4), (5) rat ventricular fibrillation (n=11), and (5) computer-simulated fibrillation. PS time-to-event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of PS formation and destruction (λ f /λ d ) determined. A systematic review was conducted to cross-validate with source data from literature., Results: In all systems, PS lifetime and interformation times were consistent with underlying Poisson renewal processes (human: λ f , 4.2%/ms±1.1 [95% CI, 4.0-5.0], λ d , 4.6%/ms±1.5 [95% CI, 4.3-4.9]; sheep: λ f , 4.4%/ms [95% CI, 4.1-4.7], λ d , 4.6%/ms±1.4 [95% CI, 4.3-4.8]; rat atrial fibrillation: λ f , 33%/ms±8.8 [95% CI, 11-55], λ d , 38%/ms [95% CI, 22-55]; rat ventricular fibrillation: λ f , 38%/ms±24 [95% CI, 22-55], λ f , 46%/ms±21 [95% CI, 31-60]; simulated fibrillation λ d , 6.6-8.97%/ms [95% CI, 4.1-6.7]; R 2 ≥0.90 in all cases). All PS distributions identified through systematic review were also consistent with an underlying Poisson renewal process., Conclusions: Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation.

Posttraumatic stress disorder (PTSD) is a global public health problem. Unfortunately, many individuals with PTSD do not receive professional care due to a lack of available providers, stigma about mental illness, and other concerns. Technology-based interventions, including mobile phone applications (apps) may be a viable means of surmounting such barriers and reaching and helping those in need. Given this potential, in 2011 the U.S Veterans Affairs National Center for PTSD released PTSD Coach, a mobile app intended to provide psycho-education and self-management tools for trauma survivors with PTSD symptoms. Emerging research on PTSD Coach demonstrates high user satisfaction, feasibility, and improvement in PTSD symptoms and other psychosocial outcomes. A model of openly sharing the app's source code and content has resulted in versions being created by individuals in six other countries: Australia, Canada, The Netherlands, Germany, Sweden, and Denmark. These versions are described, highlighting their significant adaptations, enhancements, and expansions to the original PTSD Coach app as well as emerging research on them. It is clear that the sharing of app source code and content has benefited this emerging PTSD Coach community, as well as the populations they are targeting. Despite this success, challenges remain especially reaching trauma survivors in areas where few or no other mental health resources exist., Competing Interests: Conflicts of Interest: This manuscript is partially based on: PTSD Coach around the World: A Global Perspective on a Smartphone App Designed for Self-management of PTSD Symptoms. Symposium presented at the annual meeting of the International Society for Traumatic Stress Studies, Dallas, TX, November, 2016. Chair: Christianne van der Meer.

Background: Endocannabinoids (ECs) are rapidly acting immune-modulatory lipid-signaling molecules that are important for adaptation to stressful and aversive situations.They are known to interact with glucocorticoids and other stress-responsive systems. Maladaptation to acute or chronic stress represents a major risk factor for the development of psychiatric disorders. In the present study, we administered stress doses of hydrocortisone ina prospective, randomized, placebo-controlled double blind study in patients undergoing cardiac surgery (CS) to examine the relationship between the use of glucocorticoids, plasma EC levels, and the occurrence of early postoperative cognitive dysfunction (delirium) and of later development of depression., Methods: We determined plasma levels of the ECs anandamide and 2-arachidonoylglycerol (2-AG) in CS patients of the hydrocortisone (n=56) and the placebo group(n=55) preoperatively, at postoperative day (POD) 1, at intensive care unit discharge, and at 6 months after CS(n=68). Postoperative delirium was diagnosed according to Diagnostic and Statistical Manual of the American Psychiatric Association IVth Edition (DSM-IV) criteria, and depression was determined by validated questionnaires and a standardized psychological interview (Structured Clinical Interview for DSM-IV)., Results: Stress doses of hydrocortisone did not affect plasma EC levels and the occurrence of delirium or depression. However, patients who developed deliriumon POD 1 had significantly lower preoperative 2-AG levels of the neuroprotective EC 2-AG (median values, 3.8 vs. 11.3ng/ml; p=0.03). Preoperative 2-AG concentrations were predictive of postoperative delirium (sensitivity=0.70;specificity=0.69; cutoff value=4.9 ng/ml; receiver operating characteristic curve area=0.70; 95 o/o confidence interval=0.54-0.85). Patients with depression at 6 months after CS (n=16) had significantly lower anandamide and 2-AG levels during the perioperative period., Conclusions: A low perioperative EC response may indicate an increased risk for early cognitive dysfunction and long-term depression in patients after CS. Glucocorticoids do not seem to influence this relationship.

This paper describes and analyzes agricultural water demands for Benin, West Africa. Official statistical data regarding water quantities as well as knowledge on factors influencing the demand for water are extremely rare and often reveal national trends without considering regional or local differences. Thus policy makers usually work with this estimated and aggregated data, which make it very difficult to adequately address regional and local development goals. In the framework of an interdisciplinary analysis the following paper provides insight into water quantification and detects water problems under seasonal aspects for agriculture according to regional differences. Following the definition of the Food and Agriculture Organization [FAO, 1995. Water Report 7. Irrigation in Africa in Figures. Rome] agriculture is divided into irrigation and livestock watering, which were analyzed using different field methods. The study reveals that although water supply in absolute terms seems to be sufficient in Benin, seasonal water problems occur both in irrigation and in livestock management. Thus arising seasonal water problems are not the consequence of general water scarcity but more linked to three major problems. These problems emerge from difficulties in technical equipment and financial means of farmers, from the specific local conditions influencing the access to water sources and the extraction of groundwater, and third from the overall low organizational structure of water management. Therefore regional differences as well as a general improvement of knowledge on better management structures, technical know how, and access to credits for farmers need to be considered in national strategies in order to improve the agricultural water usage in Benin.