Passive acoustic monitoring (PAM) is a cost-effective method for monitoring cetacean populations compared to techniques such as aerial and ship-based surveys. The C-POD (Cetacean POrpoise Detector) has become an integral tool in monitoring programmes globally for over a decade, providing standardised metrics of occurrence that can be compared across time and space. However, the phasing out of C-PODs following development of the new F-POD (Full waveform capture Pod) with increased sensitivity, improved train detection, and reduced false positive rates, represents an important methodological change in data collection, particularly when being introduced into existing monitoring programmes. Here, we compare the performance of the C-POD with that of its successor, the F-POD, co-deployed in a field setting for 15 months, to monitor harbour porpoise (Phocoena phocoena). While similar temporal trends in detections were found for both devices, the C-POD detected only 58% of the detection positive minutes (DPM), recorded by the F-POD. Differences in detection rates were not consistent through time making it difficult to apply a correction factor or directly compare results obtained from the two PODs. To test whether these differences in detection rates would have an effect on analyses of temporal patterns and environmental drivers of occurrence, generalised additive models (GAMs) were applied. No differences were found in seasonal patterns or the environmental correlates of porpoise occurrence (month, diel period, temperature, environmental noise, and tide). However, the C-POD failed to detect sufficient foraging buzzes to identify temporal patterns in foraging behaviour that were clearly shown by the F-POD. Our results suggest that the switch to F-PODs will have little effect on determining broad-scale seasonal patterns of occurrence, but may improve our understanding of fine-scale behaviours such as foraging. We highlight how care must be taken interpreting F-POD results as indicative of increased occurrence when used in time-series analysis.

Background: Prolonged endurance exercise is associated with an increased risk of atrial fibrillation (AF) in men. Left atrial (LA) dilation is a marker of pathological atrial remodeling and associated with AF in the general population. In athletes, however, atrial dilation is part of a physiological response to exercise, and functional parameters may help separate physiological from pathological atrial remodeling in this group. LA mechanical dispersion (LA MD) is a novel marker of LA mechanical dyssynchrony associated with AF in the general population. The associations between prolonged endurance exercise, LA MD and AF are yet to be investigated. Purpose: To investigate LA MD in male veteran athletes who had regularly participated in an annual 54-kilometer cross-country (XC) ski race in Norway with and without paroxysmal AF and to investigate the ability of LA MD to identify veteran athletes with paroxysmal AF. Methods: Two hundred and ninety-three men from four groups, veteran XC skiers with (n=57) and without (n=87) AF, and men from a non-athletic population with (n=61) and without AF (n=88) underwent an echocardiographic exam while in sinus rhythm. Using speckle-tracking echocardiography, LA strain was measured in each of the six atrial segments in an atrial-focused apical four-chamber view. We defined LA MD as the standard deviation of time-to-peak strain (SD-TPS) and report the average from three consecutive loops. Results: XC-skiers (mean age 70.9 ± 5.7 years) reported an average of 40-50 years of regular endurance exercise and an average of 16 completed annual Birkebeiner XC ski races. LA volumes were associated with both AF and athletic status (p<0.001). SD-TPS was associated with AF (p<0.001), but not with athletic status (p=0.173). We found no significant trend between years of endurance exercise and SD-TPS in individuals without AF (p=0.846). SD-TPS did not add incremental value in identifying athletes with AF in addition to clinical markers, QRS width, LA volume, and LA reservoir strain (p=0.056). Conclusion: LA MD was associated with paroxysmal AF regardless of athletic status. However, it was not associated with years of performing endurance exercise, suggesting LA MD could be a promising marker of pathological atrial remodeling in endurance athletes, less affected by physiological exercise-induced atrial remodeling than absolute volumetric measurements. We found no incremental value of LA MD in identifying veteran athletes with paroxysmal AF when LA reservoir strain was included in the model.

Working memory (WM) impairment has been well characterized in normal ageing. Various studies have explored changes in either the regional activity or the interregional connectivity underlying the WM ageing process. We proposed that brain activity and connectivity would independently alter with ageing and affect WM performance. WM was assessed with a classical N-back task during functional magnetic resonance imaging in a community-based sample comprising 168 elderly subjects (aged 55 to 86 years old). Following the rationale of background functional connectivity, we assessed age-related alterations in brain activity and seed-based interregional connectivity independently. Analyses revealed age-related decrease in the activity of the inferior parietal lobule (IPL) and an increase in the activity of the ventral anterior cingulate cortex (ACC), and the local functional dysfunctions were accompanied by alterations in their connectivity to other cortical regions. Importantly, regional activity impairments in the IPL and ACC could mediate age-related effects on accuracy rate and reaction time, respectively, and those effects were further counterbalanced by enhancement of their background functional connectivity. We thus claimed that age-induced alterations in regional activity and interregional connectivity occurred independently and contributed to WM changes in ageing. Our findings presented the way brain activity and functional connectivity interact in the late adulthood, thus providing a new perspective for understanding WM and cognitive ageing.

Disturbance and environmental change may cause communities to converge on a steady state, diverge towards multiple alternative states, or remain in long-term transience. Yet, empirical investigations of successional trajectories are rare, especially in systems experiencing multiple concurrent anthropogenic drivers of change. We examined succession in old field grassland communities subjected to disturbance and nitrogen fertilization using data from a long-term (22-year) experiment. Regardless of initial disturbance, after a decade communities converged on steady states largely determined by resource availability, where species turnover declined as communities approached dynamic equilibria. Species favored by the disturbance were those that eventually came to dominate the highly fertilized plots. Furthermore, disturbance made successional pathways more direct under low nutrients, revealing an important interaction effect between nutrients and disturbance as drivers of community change. Our results underscore the dynamical nature of grassland and old field succession, demonstrating how community properties such as beta-diversity change through transient and equilibrium states.

Background: Deprescribing is a complex process requiring a patient-centred approach. One frequently expressed deprescribing barrier is patients’ attitudes and beliefs toward reducing or stopping a medication. This study aims to identify the willingness to deprescribe predictors in a sample of Portuguese older patients. Methods: Cross-sectional study with community-dwelling patients aged ≥ 65 and taking at least one regular medication. Data collection included patients’ demographic and clinical characteristics and the Portuguese Revised Patients’ Attitudes Towards Deprescribing (rPATD) Questionnaire. Descriptive statistics were used to present patients’ characteristics and attitudes towards deprescribing. A multiple binary logistic regression analysis was performed to identify willingness to desprescribe predictors. Results: 192 participants (median age 72 years; 65.6% female) were included. A large majority (83.33%) were willing to deprescribe if recommended by their doctor. The willingness to desprescribe predictors were age (adjusted odds ratio (aOR)= 1.136), female sex (aOR= 3.036), and the rPATD concerns about stopping (aOR= 0.391). Conclusions: Most patients were willing to deprescribe if recommended by their doctor. Older age and female sex increase the odds of willingness to deprescribe; conversely, higher concerns about stopping medications decrease the odds. These findings suggest that addressing patients’ concerns about stopping their medicines may contribute to deprescribing success.

The purpose of this paper is to utilize adaptive dynamic programming to solve an optimal consensus problem for double-integrator multi-agent systems with completely unknown dynamics. In double-integrator multi-agent systems, flocking algorithms that neglect agents' inertial effect can cause unstable group behavior. Despite the fact that an inertias-independent protocol exists, the design of its control law is decided by dynamics and inertia. However, inertia in reality is difficult to measure accurately, therefore, the control gain in the consensus protocol was solved by developing adaptive dynamic programming to enable the double-integrator systems to ensure the consensus of the agents in the presence of entirely unknown dynamics. Firstly, we demonstrate in a typical example how flocking algorithms that ignore the inertial effect of agents can lead to unstable group behavior. And even though the protocol is independent of inertia, the control gain depends quite strongly on the inertia and dynamic of the agent. Then, to address these shortcomings, an online policy iteration-based adaptive dynamic programming is designed to tackle the challenge of double-integrator multi-agent systems without dynamics. Finally, simulation results are shown to prove how effective the proposed approach is.

Rotavirus A (RVA) is an important cause of acute gastroenteritis (AGE) in children. This study aims to investigate the molecular epidemiology of RVA children hospitalized with AGE in Chiang Rai, Thailand in 2018-2020 by RT-PCR. Of 302 samples, RVA was detected in 11.6% (35 samples): 11.3% (19/168) in 2018-2019 and 11.9% (16/134) in 2019-2020. Surprisingly, G8P[8] was detected as the predominant genotype at 68.4% in 2018-2019 and 81.2% in 2019-2020. In addition, other genotypes were also detected, including G1P[8] (15.8%), G2P[4] (5.3%), G3P[8] (10.5%) in 2018-2019 and G9P[8] (18.8%) in 2019-2020. Analysis of genomic constellation of G8P[8] strains, represented by RVA/Human-wt/ THA/5CR11/2019/G8P[8], revealed a DS-1-like genetic backbone: G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis of the VP7 gene showed that the DS-1-like G8P[8] strains clustered in a distinct sublineage A together with 13 G8P[8] strains reported from Thailand and China, and these sublineage A G8P[8] strains contained unique amino acid substitutions in two positions (A125S and N147D) on the VP7 antigenic epitopes. Homology modeling of the VP7 capsid protein confirmed that these two amino acid changes were located on the surface exposed area of the virion. Phylogenetic trees of the VP1, VP6, NSP2, NSP3, and NSP4 genes have demonstrated that DS-1-like G8P[8] strains in the present study and 51 DS-1-like G8P[8] reference strains published formerly clustered in separate lineages. To the best of our knowledge, this is the first report of the emergence of novel DS-1-like G8P[8] strains that might have evolved genetically through reassortment events with locally or globally circulating genotypes.

Inserts of DNA from extranuclear sources, such as organelles and microbes, are common in eukaryote nuclear genomes. However, sequence similarity between the nuclear and extranuclear DNA, and a history of multiple insertions, make the assembly of these regions challenging. Consequently, the number, sequence, and location of these vagrant DNAs cannot be reliably inferred from the genome assemblies of most organisms. We introduce two statistical methods to estimate the abundance of nuclear inserts even in the absence of a nuclear genome assembly. The first (intercept method) only requires low-coverage (<1x) sequencing data, as commonly generated for population studies of organellar and ribosomal DNAs. The second method additionally requires that a subset of the individuals carry extra-nuclear DNA with diverged genotypes. We validated our intercept method using simulations and by re-estimating the frequency of human NUMTs (nuclear mitochondrial inserts). We then applied it to the grasshopper Podisma pedestris, exceptional for both its large genome size and reports of numerous NUMT inserts, estimating that NUMTs make up 0.056% of the nuclear genome, equivalent to >500 times the mitochondrial genome size. We also re-analysed a museomics dataset of the parrot Psephotellus varius, obtaining an estimate of only 0.0043%, in line with reports from other species of bird. Our study demonstrates the utility of low-coverage high-throughput sequencing data for the quantification of nuclear vagrant DNAs. Beyond quantifying organellar inserts, these methods could also be used on endosymbiont-derived sequences. We provide an R implementation of our methods called “vagrantDNA” and code to simulate test datasets.

Background: At least 5-10% of malignancies occur secondary to an underlying cancer predisposition syndrome (CPS). For patients with a CPS, cancer surveillance is recommended with the goal of identifying malignancy earlier, in a presumably more curable form. Surveillance protocols, including imaging studies, lab work, and procedures, can be complex, differing based on age, gender, and syndrome, which may adversely affect adherence. Mobile health (mHealth) applications have been utilized in the oncology field and could help to facilitate adherence to cancer surveillance protocols. Methods: Applying a user-centered mobile app design approach, patients with a CPS and/or primary caregivers were interviewed to identify current methods for care management and barriers to compliance with recommended surveillance protocols. Broad themes from these interviews informed the design of the mobile app, HomeTown, subsequently evaluated by usability experts. The design was then converted into software code in phases, evaluated by patients and caregivers in an iterative fashion. User population growth and app usage data were assessed. Results: Common themes identified include general distress surrounding surveillance protocol scheduling and results, difficulty remembering medical history, assembling a care team, and seeking resources for self-education. These themes were translated into specific functional app features including push reminders, syndrome-specific surveillance recommendations, ability to annotate visits and results, storage of medical histories, and links to reliable educational resources. Conclusions: Families with CPS demonstrate a desire for mHealth tools to facilitate adherence to cancer surveillance protocols, reduce related distress, relay medical information, and provide educational resources. HomeTown may be a useful tool for engaging this patient population.

Splenic hematoma following an acute pancreatitis is a rare complication which is thought to be due to the distribution of pancreatic exudates to the spleen. We presented a case of a 44-year-old patient with acute pancreatitis who developed splenic hematoma. He responded well to conservative management and the hematoma resolved.

We carried out 3-D simulations of monodisperse particle suspensions subjected to a constant shear rate with the view to investigate the effect of electrical double layers around the particles on apparent suspension viscosities. To this end, expressions for Debye length, zeta potential and ionic strength (pH) of the liquid were incorporated into our in-house lattice Boltzmann code that uses the Immersed Boundary method and includes sub-grid lubrication models. We varied the solids concentration and particle radius, keeping the particle Reynolds number equal to 0.1. We report on results with respect to the effect of pH (in the range 9 through 12) and Debye length on apparent viscosity and spatial suspension structures, particularly at higher solids volume fractions, and on the effect of flow reversals.

The use of endocardial pacing in patients with univentricular hearts is limited. However, it may be the better option when the risk of surgery is high. We report a case of complete heart block who underwent left ventricular endocardial pacing due to the high risk of epicardial lead placement.

I am not sure this editorial comment deserves an abstract. Plesae advise.

Left anterior descending (LAD) coronary arterial injury is an underappreciated and rare consequence of ablation in the right ventricular outflow tract (RVOT). The authors present five cases of acute or subacute LAD injury after RVOT ablation. Most patients had fairly extensive ablation and two had coincident cardiac perforation. The patients reported also had a strikingly similar ECG morphology of their spontaneous ventricular arrhythmias. The authors’ report serves an important cautionary tale regarding ablation of intramural septal VAs.

Predictive Modeling of Lead Durability, An Important Step ForwardGeorge H. Crossley MD, FHRS, FACCVanderbilt Heart and Vascular Institute, Nashville, TN; and Cardiovascular Diseases Section, Vanderbilt University School of MedicineRWI: Dr. Crossley consults for Medtronic, Boston Scientific, and Phillips.Running Title: Lead Durability AnalysisWord Count: 893

Radiofrequency (RF) ablation for the treatment of atrial fibrillation has gained widespread acceptance since the concept was introduced by Haissaguerre et al a quarter of a century ago. High power short duration ablation has been widely adopted in the management of atrial fibrillation. Evidence for combining lesion size index and high power short duration ablation is lacking. In this issue of the journal, Cai et al evaluated the combination of HPSD with LSI with a focus on long-term efficacy.

Transoral robotic surgery (TORS) has evolved into a common surgical modality used to treat primarily oropharyngeal malignant and benign pathologies. The single port Intuitive Surgical da Vinci surgical robotics system facilitates access to the hypopharynx and cervical esophagus. We aim to describe our approach and advantages of the technique.

Viral vectors for gene therapy, such as recombinant Adeno-Associated Viruses (rAAV), are produced in Human Embryonic Kidney (HEK) 293 cells. However, the presence of the SV40 T-antigen-encoding CDS SV40GP6 and SV40GP7 in the HEK293T genome raises safety issues when these cells are used in manufacturing for clinical purposes. We developed a new T-antigen-negative HEK cell line from ExcellGene’s proprietary HEKExpress®, using the CRISPR-Cas9 strategy. We obtained a high number of clonally-derived cell populations and all of them were demonstrated T-antigen negative. Stability study and AAV production evaluation showed that the deletion of the T-antigen-encoding locus did not impact neither cell growth nor viability nor productivity. The resulting CMC-compliant cell line, named HEKzeroT®, is able to produce high AAV titers, from small to large scale.