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Neuroscience Apr 2021Perceiving the temporal regularity in a sequence of repetitive sensory events facilitates the preparation and execution of relevant behaviors with tight temporal...
Perceiving the temporal regularity in a sequence of repetitive sensory events facilitates the preparation and execution of relevant behaviors with tight temporal constraints. How we estimate temporal regularity from repeating patterns of sensory stimuli is not completely understood. We developed a decision-making task in which participants had to decide whether a train of visual, auditory, or tactile pulses, had a regular or an irregular temporal pattern. We tested the hypothesis that subjects categorize stimuli as irregular by accumulating the time differences between the predicted and observed times of sensory pulses defining a temporal rhythm. Results suggest that instead of waiting for a single large temporal deviation, participants accumulate timing-error signals and judge a pattern as irregular when the amount of evidence reaches a decision threshold. Model fits of bounded integration showed that this accumulation occurs with negligible leak of evidence. Consistent with previous findings, we show that participants perform better when evaluating the regularity of auditory pulses, as compared with visual or tactile stimuli. Our results suggest that temporal regularity is estimated by comparing expected and measured pulse onset times, and that each prediction error is accumulated towards a threshold to generate a behavioral choice.
Topics: Auditory Perception; Humans; Touch
PubMed: 33549694
DOI: 10.1016/j.neuroscience.2021.01.035 -
PloS One 2021Identifying coordinated activity within complex systems is essential to linking their structure and function. We study collective activity in networks of pulse-coupled...
Identifying coordinated activity within complex systems is essential to linking their structure and function. We study collective activity in networks of pulse-coupled oscillators that have variable network connectivity and integrate-and-fire dynamics. Starting from random initial conditions, we see the emergence of three broad classes of behaviors that differ in their collective spiking statistics. In the first class ("temporally-irregular"), all nodes have variable inter-spike intervals, and the resulting firing patterns are irregular. In the second ("temporally-regular"), the network generates a coherent, repeating pattern of activity in which all nodes fire with the same constant inter-spike interval. In the third ("chimeric"), subgroups of coherently-firing nodes coexist with temporally-irregular nodes. Chimera states have previously been observed in networks of oscillators; here, we find that the notions of temporally-regular and chimeric states encompass a much richer set of dynamical patterns than has yet been described. We also find that degree heterogeneity and connection density have a strong effect on the resulting state: in binomial random networks, high degree variance and intermediate connection density tend to produce temporally-irregular dynamics, while low degree variance and high connection density tend to produce temporally-regular dynamics. Chimera states arise with more frequency in networks with intermediate degree variance and either high or low connection densities. Finally, we demonstrate that a normalized compression distance, computed via the Lempel-Ziv complexity of nodal spike trains, can be used to distinguish these three classes of behavior even when the phase relationship between nodes is arbitrary.
Topics: Computer Simulation; Humans; Models, Neurological; Nerve Net; Neural Networks, Computer; Neural Pathways
PubMed: 34379694
DOI: 10.1371/journal.pone.0256034 -
Cardiovascular Pathology : the Official... May 2024Constrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related...
AIM
Constrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related disease (IgG4-RD) is a systemic fibro-inflammatory disease characterised by the infiltration of IgG4-immunopositive plasmacytes and high serum IgG4 levels that frequently shape tumorous lesions. Although pericardial involvement of IgG4-RD is rare, with indications of CP, pericardial effusion and irregular masses, the clinical and pathological features remain unclear. In this study, we examined the relationship between CP and IgG4-RD.
METHODS
Among 35 thick-walled CP cases (histologically pericardial thickening ≥2 mm), eight cases were aetiology identified. Using the diagnostic criteria for IgG4-RD, 11 cases were classified as IgG4-CP, whereas the remainder were considered true idiopathic CP (16 cases) and the clinical pathological features were evaluated.
RESULTS
Compared with the other groups, the IgG4-CP group was more common in men and associated with low-grade fever and massive pericardial effusion with frequent recurrence. Deaths resulting from heart failure occurred in a few cases of the IgG4-CP group, but not in other groups. An increase in C-reactive protein and a high positivity rate of anti-nuclear antibodies frequently occurred in the IgG4-CP group. Histologically, the IgG4-CP group included lymphoid follicle, eosinophil infiltration and few calcifications.
CONCLUSIONS
Pericardial IgG4-RD occurs not only as nodular lesions, but also as thick-walled CP, and accounts for approximately 40% of thick-walled CP cases of unknown cause. The predominant clinical characteristic was refractory and recurrent pericardial effusion. Recognising IgG4-RD as a cause of CP is important to initiate appropriate therapy.
PubMed: 38825060
DOI: 10.1016/j.carpath.2024.107665 -
Biomedical Reports Nov 2020Thalassemia is a genetic haematological disorder that arises due to defects in the α and β-globin genes. Worldwide, 0.3-0.4 million children are born with... (Review)
Review
Thalassemia is a genetic haematological disorder that arises due to defects in the α and β-globin genes. Worldwide, 0.3-0.4 million children are born with haemoglobinopathies per year. Thalassemic patients, as well as their families, face various serious clinical, socio-economic, and psychosocial challenges throughout their life. Different therapies are available in clinical practice to minimize the suffering of thalassemic patients to some extent and potentially cure the disease. Predominantly, patients undergo transfusion therapy to maintain their haemoglobin levels. Due to multiple transfusions, the iron levels in their bodies are elevated. Iron overload results in damage to body organs, resulting in heart failure, liver function failure or endocrine failure, all of which are commonly observed. Certain drugs have been developed to enhance the expression of the γ-gene, which ultimately results in augmentation of fetal haemoglobin (HbF) levels and total haemoglobin levels in the body. However, its effectiveness is dependent on the genetic makeup of the individual patient. At present, allogeneic haematopoietic Stem Cell Transplantation (HSCT) is the only practically available option with a high curative rate. However, the outcome of HSCT is strongly influenced by factors such as age at transplantation, irregular iron chelation history before transplantation, histocompatibility, and source of stem cells. Gene therapy using the lentiglobin vector is the most recent method for cure without any mortality, graft rejection and clonal dominance issues. However, delayed platelet engraftment is being reported in some patients. Genome editing is a novel approach which may be used to treat patients with thalassemia; it makes use of targeted nucleases to correct the mutations in specific DNA sequences and modify the sequence to the normal wild-type sequence. To edit the genome at the required sites, CRISPR/Cas9 is an efficient and accurate tool that is used in various genetic engineering programs. Genome editing mediated by CRISPR/Cas9 has the ability to restore the normal β-globin function with minimal side effects. Using CRISPR/Cas9, expression of can be downregulated along with increased production of HbF. However, these genome editing tools are still under trials. CRISPR/Cas9 has can be used for precise transcriptional regulation, genome modification and epigenetic editing. Additional research is required in this regard, as CRISPR/Cas9 may potentially exhibit off-target activity and there are legal and ethical considerations regarding its use.
PubMed: 32953110
DOI: 10.3892/br.2020.1355 -
Heart Failure Reviews Nov 2022Many patients with persistent, chronic, or frequently recurring paroxysmal atrial fibrillation (AF) may develop a tachycardiomyopathy (TCM) with left ventricular (LV)...
Many patients with persistent, chronic, or frequently recurring paroxysmal atrial fibrillation (AF) may develop a tachycardiomyopathy (TCM) with left ventricular (LV) dysfunction and heart failure (HF), which is reversible upon restoration and maintenance of sinus rhythm, when feasible, or via better and tighter ventricular rate (VR) control. Mechanisms involved in producing this leading cause of TCM (AF-TCM) include loss of atrial contraction, irregular heart rate, fast VR, neurohumoral activation, and structural myocardial changes. The most important of all mechanisms relates to optimal VR control, which seems to be an elusive target. Uncontrolled AF may also worsen preexisting LV dysfunction and exacerbate HF symptoms. Data, albeit less robust, also point to deleterious effects of slow VRs on LV function. Thus, a J-shaped relationship between VR and clinical outcome has been suggested, with the optimal VR control hovering at ~ 65 bpm, ranging between 60 and 80 bpm; VRs above and below this range may confer higher morbidity and mortality rates. A convergence of recent guidelines is noted towards a stricter rather than a more lenient VR control with target heart rate < 80 bpm at rest and < 110 bpm during moderate exercise which seems to prevent TCM or improve LV function and exercise capacity and relieve TCM-related symptoms and signs. Of course, restoring and maintaining sinus rhythm is always a most desirable target, when feasible, either with drugs or more likely with ablation. All these issues are herein reviewed, current guidelines are discussed and relevant data are tabulated and pictorially illustrated.
Topics: Atrial Fibrillation; Catheter Ablation; Heart Atria; Heart Failure; Humans; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 35318562
DOI: 10.1007/s10741-022-10221-1 -
IEEE Transactions on Neural Systems and... 2021Retinal prostheses must be able to activate cells in a selective way in order to restore high-fidelity vision. However, inadvertent activation of far-away retinal...
OBJECTIVE
Retinal prostheses must be able to activate cells in a selective way in order to restore high-fidelity vision. However, inadvertent activation of far-away retinal ganglion cells (RGCs) through electrical stimulation of axon bundles can produce irregular and poorly controlled percepts, limiting artificial vision. In this work, we aim to provide an algorithmic solution to the problem of detecting axon bundle activation with a bi-directional epiretinal prostheses.
METHODS
The algorithm utilizes electrical recordings to determine the stimulation current amplitudes above which axon bundle activation occurs. Bundle activation is defined as the axonal stimulation of RGCs with unknown soma and receptive field locations, typically beyond the electrode array. The method exploits spatiotemporal characteristics of electrically-evoked spikes to overcome the challenge of detecting small axonal spikes.
RESULTS
The algorithm was validated using large-scale, single-electrode and short pulse, ex vivo stimulation and recording experiments in macaque retina, by comparing algorithmically and manually identified bundle activation thresholds. For 88% of the electrodes analyzed, the threshold identified by the algorithm was within ±10% of the manually identified threshold, with a correlation coefficient of 0.95.
CONCLUSION
This works presents a simple, accurate and efficient algorithm to detect axon bundle activation in epiretinal prostheses.
SIGNIFICANCE
The algorithm could be used in a closed-loop manner by a future epiretinal prosthesis to reduce poorly controlled visual percepts associated with bundle activation. Activation of distant cells via axonal stimulation will likely occur in other types of retinal implants and cortical implants, and the method may therefore be broadly applicable.
Topics: Axons; Electric Stimulation; Retina; Retinal Ganglion Cells; Visual Prosthesis
PubMed: 34784278
DOI: 10.1109/TNSRE.2021.3128486 -
PloS One 2019Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with increased risk of stroke and congestive heart failure. Lead-I...
Lead-I ECG for detecting atrial fibrillation in patients attending primary care with an irregular pulse using single-time point testing: A systematic review and economic evaluation.
BACKGROUND
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with increased risk of stroke and congestive heart failure. Lead-I electrocardiogram (ECG) devices are handheld instruments that can detect AF at a single-time point.
PURPOSE
To assess the diagnostic test accuracy, clinical impact and cost effectiveness of single-time point lead-I ECG devices compared with manual pulse palpation (MPP) followed by a 12-lead ECG for the detection of AF in symptomatic primary care patients with an irregular pulse.
METHODS
Electronic databases (MEDLINE, MEDLINE Epub Ahead of Print and MEDLINE In-Process, EMBASE, PubMed and Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database) were searched to March 2018. Two reviewers screened the search results, extracted data and assessed study quality. Summary estimates of diagnostic accuracy were calculated using bivariate models. Cost-effectiveness was evaluated using an economic model consisting of a decision tree and two cohort Markov models.
RESULTS
Diagnostic accuracy The diagnostic accuracy (13 publications reporting on nine studies) and clinical impact (24 publications reporting on 19 studies) results are derived from an asymptomatic population (used as a proxy for people with signs or symptoms of AF). The summary sensitivity of lead-I ECG devices was 93.9% (95% confidence interval [CI]: 86.2% to 97.4%) and summary specificity was 96.5% (95% CI: 90.4% to 98.8%). Cost effectiveness The de novo economic model yielded incremental cost effectiveness ratios (ICERs) per quality adjusted life year (QALY) gained. The results of the pairwise analysis show that all lead-I ECG devices generate ICERs per QALY gained below the £20,000-£30,000 threshold. Kardia Mobile is the most cost effective option in a full incremental analysis. Lead-I ECG tests may identify more AF cases than the standard diagnostic pathway. This comes at a higher cost but with greater patient benefit in terms of mortality and quality of life.
LIMITATIONS
No published data evaluating the diagnostic accuracy, clinical impact or cost effectiveness of lead-I ECG devices for the target population are available.
CONCLUSIONS
The use of single-time point lead-I ECG devices in primary care for the detection of AF in people with signs or symptoms of AF and an irregular pulse appears to be a cost effective use of NHS resources compared with MPP followed by a 12-lead ECG, given the assumptions used in the base case model.
REGISTRATION
The protocol for this review is registered on PROSPERO as CRD42018090375.
Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cost-Benefit Analysis; Electrocardiography; Female; Humans; Male; Markov Chains; Middle Aged; Primary Health Care; Pulse
PubMed: 31869370
DOI: 10.1371/journal.pone.0226671 -
PloS One 2022Atrial fibrillation (AF) remain a prevalent undiagnosed condition frequently encountered in primary care.
BACKGROUND
Atrial fibrillation (AF) remain a prevalent undiagnosed condition frequently encountered in primary care.
OBJECTIVE
We aimed to find the parameters that optimize the diagnostic accuracy of pulse palpation to detect AF. We also aimed to create a simple algorithm for selecting which individuals would benefit from pulse palpation and, if positive, receive an ECG to detect AF.
METHODS
Nurses from four Cardiology outpatient clinics palpated 7,844 pulses according to a randomized list of arterial territories and durations of measure and immediately followed by a 12-lead ECG, which we used as the reference standard. We calculated the sensitivity and specificity of the palpation parameters. We also assessed whether diagnostic accuracy depended on the nurse's experience or on a list of clinical factors of the patients. With this information, we estimated the positive predictive values and false omission rates according to very few clinical factors readily available in primary care (age, sex, and diagnosis of heart failure) and used them to create the algorithm.
RESULTS
The parameters associated with the highest diagnostic accuracy were palpation of the radial artery and classifying as irregular those palpations in which the nurse was uncertain about pulse regularity or unable to palpate pulse (sensitivity = 79%; specificity = 86%). Specificity decreased with age. Neither the nurse's experience nor any investigated clinical factor influenced diagnostic accuracy. We provide the algorithm to select the ≥40 years old individuals that would benefit from a pulse palpation screening: a) do nothing in <60 years old individuals without heart failure; b) do ECG in ≥70 years old individuals with heart failure; c) do radial pulse palpation in the remaining individuals and do ECG if the pulse is irregular or you are uncertain about its regularity or unable to palpate it.
CONCLUSIONS
Opportunistic screening for AF using optimal pulse palpation in candidate individuals according to a simple algorithm may have high effectiveness in detecting AF in primary care.
Topics: Adult; Aged; Ambulatory Care Facilities; Atrial Fibrillation; Cardiology; Electrocardiography; Heart Failure; Humans; Mass Screening; Middle Aged; Palpation; Pulse
PubMed: 35446875
DOI: 10.1371/journal.pone.0266955 -
Journal of Speech, Language, and... Jan 2023Vocal fold asymmetry creates irregular entrainments and modulations in voice, which may lead to rough perceptual quality. The presence of asymmetry can also cause...
PURPOSE
Vocal fold asymmetry creates irregular entrainments and modulations in voice, which may lead to rough perceptual quality. The presence of asymmetry can also cause mid-phonation bifurcations where a small change in the phonatory system causes a drastic change in vibration pattern, resulting in transitions in and out of rough voice. This study surveys sustained phonation recordings of speakers with the diagnoses of vocal fold polyp or unilateral vocal fold paralysis to investigate the resulting voice patterns.
METHOD
This retrospective study observed 71 sustained phonation recordings from 48 patients. Segments with distinctive signal patterns were identified within each recording with narrowband spectrogram and computer-assisted analysis of spectral peaks.
RESULTS
Phonation segmentation yielded 240 segments across all the recordings. Five voice patterns were recognized: (regularly or irregularly) entrained, modulated, uncoupled, unstable, and pulsed. Thirty-six patients (75%) exhibited irregular patterns. No single irregular pattern lasted for the entire phonation and was always accompanied by at least one mid-phonation bifurcation. Durations of the irregular segments ( = 0.4 s) were significantly shorter than the segments with the regular pattern ( = 1.4 s).
CONCLUSIONS
The results suggest that vocal fold pathology frequently introduces dynamic vibratory patterns that affect both the acoustic signals and perceptions. Due to these abnormalities, it is important for clinical voice assessment protocols, both perceptual and acoustic, to account for these possible bifurcations, irregular signal patterns, and their tendencies.
Topics: Humans; Vocal Cords; Retrospective Studies; Voice; Phonation; Acoustics; Vibration
PubMed: 36472934
DOI: 10.1044/2022_JSLHR-21-00499 -
Frontiers in Physiology 2022The response to atrial fibrillation (AF) treatment is differing widely among patients, and a better understanding of the factors that contribute to these differences is...
The response to atrial fibrillation (AF) treatment is differing widely among patients, and a better understanding of the factors that contribute to these differences is needed. One important factor may be differences in the autonomic nervous system (ANS) activity. The atrioventricular (AV) node plays an important role during AF in modulating heart rate. To study the effect of the ANS-induced activity on the AV nodal function in AF, mathematical modelling is a valuable tool. In this study, we present an extended AV node model that incorporates changes in autonomic tone. The extension was guided by a distribution-based sensitivity analysis and incorporates the ANS-induced changes in the refractoriness and conduction delay. Simulated RR series from the extended model driven by atrial impulse series obtained from clinical tilt test data were qualitatively evaluated against clinical RR series in terms of heart rate, RR series variability and RR series irregularity. The changes to the RR series characteristics during head-down tilt were replicated by a 10% decrease in conduction delay, while the changes during head-up tilt were replicated by a 5% decrease in the refractory period and a 10% decrease in the conduction delay. We demonstrate that the model extension is needed to replicate ANS-induced changes during tilt, indicating that the changes in RR series characteristics could not be explained by changes in atrial activity alone.
PubMed: 36187793
DOI: 10.3389/fphys.2022.976468