Did COVID-19 ICU patient mortality risk increase as Colorado hospitals filled? A retrospective cohort study.

OBJECTIVES: To assess whether increasing levels of hospital stress-measured by intensive care unit (ICU) bed occupancy (primary), ventilators in use and emergency department (ED) overflow-were associated with decreasing COVID-19 ICU patient survival in Colorado ICUs during the pre-Delta, Delta and Omicron variant eras. DESIGN: A retrospective cohort study using discrete-time survival models, fit with generalised estimating equations. SETTING: 34 hospital systems in Colorado, USA, with the highest patient volume ICUs during the COVID-19 pandemic. PARTICIPANTS: 9196 non-paediatric SARS-CoV-2 patients in Colorado hospitals admitted once to an ICU between 1 August 2020 and 1 March 2022 and followed for 28 days. OUTCOME MEASURES: Death or discharge to hospice. RESULTS: For Delta-era COVID-19 ICU patients in Colorado, the odds of death were estimated to be 26% greater for patients exposed every day of their ICU admission to a facility experiencing its all-era 75th percentile ICU fullness or above, versus patients exposed for none of their days (OR: 1.26; 95% CI: 1.04 to 1.54; p=0.0102), adjusting for age, sex, length of ICU stay, vaccination status and hospital quality rating. For both Delta-era and Omicron-era patients, we also detected significantly increased mortality hazard associated with high ventilator utilisation rates and (in a subset of facilities) states of ED overflow. For pre-Delta-era patients, we estimated relatively null or even protective effects for the same fullness exposures, something which provides a meaningful contrast to previous studies that found increased hazards but were limited to pre-Delta study windows. CONCLUSIONS: Overall, and especially during the Delta era (when most Colorado facilities were at their fullest), increasing exposure to a fuller hospital was associated with an increasing mortality hazard for COVID-19 ICU patients.

Comparing the compensatory reserve metric obtained from invasive arterial measurements and photoplethysmographic volume-clamp during simulated hemorrhage.

PURPOSE: The compensatory reserve metric (CRM) is a novel tool to predict cardiovascular decompensation during hemorrhage. The CRM is traditionally computed using waveforms obtained from photoplethysmographic volume-clamp (PPGVC), yet invasive arterial pressures may be uniquely available. We aimed to examine the level of agreement of CRM values computed from invasive arterial-derived waveforms and values computed from PPGVC-derived waveforms. METHODS: Sixty-nine participants underwent graded lower body negative pressure to simulate hemorrhage. Waveform measurements from a brachial arterial catheter and PPGVC finger-cuff were collected. A PPGVC brachial waveform was reconstructed from the PPGVC finger waveform. Thereafter, CRM values were computed using a deep one-dimensional convolutional neural network for each of the following source waveforms; (1) invasive arterial, (2) PPGVC brachial, and (3) PPGVC finger. Bland-Altman analyses were used to determine the level of agreement between invasive arterial CRM values and PPGVC CRM values, with results presented as the Mean Bias [95% Limits of Agreement]. RESULTS: The mean bias between invasive arterial- and PPGVC brachial CRM values at rest, an applied pressure of -45mmHg, and at tolerance was 6% [-17%, 29%], 1% [-28%, 30%], and 0% [-25%, 25%], respectively. Additionally, the mean bias between invasive arterial- and PPGVC finger CRM values at rest, applied pressure of -45mmHg, and tolerance was 2% [-22%, 26%], 8% [-19%, 35%], and 5% [-15%, 25%], respectively. CONCLUSION: There is generally good agreement between CRM values obtained from invasive arterial waveforms and values obtained from PPGVC waveforms. Invasive arterial waveforms may serve as an alternative for computation of the CRM.

Lactate transport inhibition therapeutically reprograms fibroblast metabolism in experimental pulmonary fibrosis.

Myofibroblast differentiation, essential for driving extracellular matrix synthesis in pulmonary fibrosis, requires increased glycolysis. While glycolytic cells must export lactate, the contributions of lactate transporters to myofibroblast differentiation are unknown. In this study, we investigated how MCT1 and MCT4, key lactate transporters, influence myofibroblast differentiation and experimental pulmonary fibrosis. Our findings reveal that inhibiting MCT1 or MCT4 reduces TGFß-stimulated pulmonary myofibroblast differentiation in vitro and decreases bleomycin-induced pulmonary fibrosis in vivo. Through comprehensive metabolic analyses, including bioenergetics, stable isotope tracing, metabolomics, and imaging mass spectrometry in both cells and mice, we demonstrate that inhibiting lactate transport enhances oxidative phosphorylation, reduces reactive oxygen species production, and diminishes glucose metabolite incorporation into fibrotic lung regions. Furthermore, we introduce VB253, a novel MCT4 inhibitor, which ameliorates pulmonary fibrosis in both young and aged mice, with comparable efficacy to established antifibrotic therapies. These results underscore the necessity of lactate transport for myofibroblast differentiation, identify MCT1 and MCT4 as promising pharmacologic targets in pulmonary fibrosis, and support further evaluation of lactate transport inhibitors for patients for whom limited therapeutic options currently exist.

Effects of Eucalyptus wood and leaf litter on saproxylic insects in the southeastern United States.

Although Eucalyptus is widely planted outside its native range for timber and pulp production, the effects of these exotic plantations on biodiversity relative to native semi-natural forests or plantations of native tree species remain incompletely understood. Here, we compare the diversity of saproxylic beetles (Coleoptera) and true bugs (Hemiptera) between non-native Eucalyptus benthamii Maiden and Cambage (Camden white gum) and native Pinus taeda L. (loblolly pine) stands on the upper Coastal Plain of South Carolina, U.S.A. We sampled insects emerging from logs of both species placed in both stand types after 1, 2, 6, and 12 months in the field. Beetle and true bug richness and diversity were both significantly lower from eucalypt than from pine wood. Moreover, the two communities were compositionally distinct. Whereas pine supported many species of host-specific phloeoxylophagous beetles, most species collected from eucalypts were mycophagous or predatory taxa capable of utilizing a wide range of hosts. Species richness did not differ between logs placed in eucalypt vs. pine stands but Shannon's diversity was significantly higher in the eucalypt stands, possibly due to greater sun exposure in the latter. Contrary to a previous study, we found no support for the idea that eucalypt litter reduces the diversity of saproxylic insects. Our findings add to the growing body of evidence that non-native plantations are less favorable to biodiversity than those consisting of native tree species.

Consensus practice recommendations for management of gastrointestinal dysfunction in Parkinson disease.

BACKGROUND: Gastrointestinal (GI) dysfunction is a common non-motor feature of Parkinson disease (PD). GI symptoms may start years before the onset of motor symptoms and impair quality of life. Robust clinical trial data is lacking to guide screening, diagnosis and treatment of GI dysfunction in PD. OBJECTIVE: To develop consensus statements on screening, diagnosis, and treatment of GI dysfunction in PD. METHODS: The application of a modified Delphi panel allowed for the synthesis of expert opinions into clinical statements. Consensus was predefined as a level of agreement of 100 % for each item. Five virtual Delphi rounds were held. Two movement disorders neurologists reviewed the literature on GI dysfunction in PD and developed draft statements based on the literature review. Draft statements were distributed among the panel that included five movement disorder neurologists and two gastroenterologists, both experts in GI dysmotility and its impact on PD symptoms. All members reviewed the statements and references in advance of the virtual meetings. In the virtual meetings, each statement was discussed, edited, and a vote was conducted. If there was not 100 % consensus, further discussions and modifications ensued until there was consensus. RESULTS: Statements were developed for screening, diagnosis, and treatment of common GI symptoms in PD and were organized by anatomic segments: oral cavity and esophagus, stomach, small intestine, and colon and anorectum. CONCLUSIONS: These consensus recommendations offer a practical framework for the diagnosis and treatment of GI dysfunction in PD.

Spatial organisation of fungi in soil biocrusts of the Kalahari is related to bacterial community structure and may indicate ecological functions of fungi in drylands.

Biological soil crusts, or biocrusts, are microbial communities found in soil surfaces in drylands and in other locations where vascular plant cover is incomplete. They are functionally significant for numerous ecosystem services, most notably in the C fixation and storage due to the ubiquity of photosynthetic microbes. Whereas carbon fixation and storage have been well studied in biocrusts, the composition, function and characteristics of other organisms in the biocrust such as heterotrophic bacteria and especially fungi are considerably less studied and this limits our ability to gain a holistic understanding of biocrust ecology and function. In this research we characterised the fungal community in biocrusts developed on Kalahari Sand soils from a site in southwest Botswana, and combined these data with previously published bacterial community data from the same site. By identifying organisational patterns in the community structure of fungi and bacteria, we found fungi that were either significantly associated with biocrust or the soil beneath biocrusts, leading to the conclusion that they likely perform functions related to the spatial organisation observed. Furthermore, we showed that within biocrusts bacterial and fungal community structures are correlated with each other i.e., a change in the bacterial community is reflected by a corresponding change in the fungal community. Importantly, this correlation but that this correlation does not occur in nearby soils. We propose that different fungi engage in short-range and long-range interactions with dryland soil surface bacteria. We have identified fungi which are candidates for further studies into their potential roles in biocrust ecology at short ranges (e.g., processing of complex compounds for waste management and resource provisioning) and longer ranges (e.g., translocation of resources such as water and the fungal loop model). This research shows that fungi are likely to have a greater contribution to biocrust function and dryland ecology than has generally been recognised.

Physiologic validation of the compensatory reserve metric obtained from pulse oximetry: A step towards advanced medical monitoring on the battlefield.

BACKGROUND: The Compensatory Reserve Metric (CRM) provides a time sensitive indicator of hemodynamic decompensation. However, its in-field utility is limited due to the size and cost-intensive nature of standard vital sign monitors or photoplethysmographic volume-clamp (PPGVC) devices used to measure arterial waveforms. In this regard, photoplethysmographic measurements obtained from pulse oximetry (PPGPO) may serve as a useful, portable alternative. This study aimed to validate CRM values obtained using PPGPO. METHODS: Forty-nine healthy adults (25 females) underwent a graded lower body negative pressure (LBNP) protocol to simulate hemorrhage. Arterial waveforms were sampled using PPGPO and PPGVC. The CRM was calculated using a one-dimensional convolutional neural network. Cardiac output and stroke volume were measured using PPGVC. A brachial artery catheter was used to measure intraarterial pressure. A 3-lead ECG was used to measure heart rate. Fixed-effect linear mixed models with repeated measures were used to examine the association between CRM values and physiologic variables. Log-rank analyses were used to examine differences in shock determination during LBNP between monitored hemodynamic parameters. RESULTS: The median LBNP stage reached was 70 mmHg (Range: 45-100 mmHg). Relative to baseline, at tolerance there was a 47±12% reduction in stroke volume, 64±27% increase in heart rate, and 21±7% reduction in systolic blood pressure (P<0.001 for all). CRM values obtained with both PPGPO and PPGVC were associated with changes in heart rate (P<0.001), stroke volume (P<0.001), and pulse pressure (P<0.001). Furthermore, they provided an earlier detection of hemodynamic shock relative to the traditional metrics of shock index (P<0.001 for both), systolic blood pressure (P<0.001 for both), and heart rate (P=0.001 for both). CONCLUSION: The CRM obtained from PPGPO provides a valid, time-sensitized prediction of hemodynamic decompensation, opening the door to provide military medical personnel noninvasive in-field advanced capability for early detection of hemorrhage and imminent onset of shock. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria, Level IV.

Mass Spectrometry-Based Assessment of M-protein in Peripheral Blood During Maintenance Therapy in Multiple Myeloma.

Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during post-transplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of post-transplant maintenance with either carfilzomib, lenalidomide, dexamethasone or lenalidomide alone were analyzed using EXENT MS methodology. We established feasibility of measuring MRD by MS in PB in the post-transplant setting, despite unavailability of pre-treatment calibration samples. There was high agreement between MRD by MS in PB and paired BM MRD results at the 10-5 threshold, assessed by either next generation sequencing (NGS) or multiparameter flow cytometry (MFC) (70% and 67%, respectively). Agreement between PB MS and both BM MRD methods was lowest early after transplant and increased with time. MS negativity was associated with improved progression-free survival (PFS), which in landmark analysis reached statistical significance after 18 cycles post-transplant. Combined PB/BM MRD negativity by MFC or NGS was associated with superior PFS compared to MRD negativity by only one modality. Sustained MS negativity carried similar prognostic performance to sustained BM MRD negativity at the 10-5 threshold. Overall, post-transplant MS assessment was feasible and provided additional prognostic information to BM MRD negativity. Further studies are needed to confirm the role and optimal timing of MS in disease evaluation algorithms. The ATLAS trial is registered at www.clinicaltrials.gov as #NCT02659293.

A de novo germline RUNX1 variant preceding development of concurrent T-lymphoblastic leukemia and myelodysplastic syndrome.

Germline variants of the RUNX1 gene are associated with RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies (RUNX1-FPDMM), which is characterized by an increased risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. Patients with FPDMM have also been described to develop B- or T-cell acute lymphoblastic leukemia. We present a pediatric patient with RUNX1-FPDMM that evolved into concurrent MDS and T-cell acute lymphoblastic leukemia after a decade of monitoring with serial blood counts. We aim to highlight the treatment challenges and clinical decision-making that may be anticipated in this unique disorder, as well as the potentially curative role for allogenic hematopoietic stem cell transplant in the first complete remission.

A New Functional Threshold for Minimally Invasive Lobectomy.

OBJECTIVE: To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV1/ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy. SUMMARY BACKGROUND DATA: Although MIS is associated with better postoperative outcomes than open surgery, MIS uses risk-assessment algorithms developed for open surgery. Moreover, several different definitions of cardiopulmonary complications are used for assessment. METHODS: All patients who underwent MIS lobectomy for clinical stage I-II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV1/ppoDLCO threshold of <45% was compared against that of the current guideline threshold of <60%. Three different definitions of cardiopulmonary complications were compared: Society of Thoracic Surgeons (STS), European Society of Thoracic Surgeons (ESTS), and Berry et al. RESULTS: In 946 patients, the ppoFEV1/ppoDLCO threshold of <45% was associated with a higher proportion correctly classified (79% [95% CI, 76%-81%] vs. 65% [95% CI, 62%-68%]; P<0.001). The complication with the biggest difference in incidence between ppoFEV1/ppoDLCO of 45%-60% and >60% was prolonged air leak (33 [13%] vs. 34 [6%]; P<0.001). The predicted probability curves for cardiopulmonary complications were higher for the STS definition than for the ESTS or Berry definitions across ppoFEV1 and ppoDLCO values. CONCLUSIONS: The ppoFEV1/ppoDLCO threshold of <45% more accurately classified patients for cardiopulmonary complications after MIS lobectomy, emphasizing the need for updated risk-assessment guidelines for MIS lobectomy to optimize additional cardiopulmonary function evaluation.

No evidence that averaging voices influences attractiveness.

Vocal attractiveness influences important social outcomes. While most research on the acoustic parameters that influence vocal attractiveness has focused on the possible roles of sexually dimorphic characteristics of voices, such as fundamental frequency (i.e., pitch) and formant frequencies (i.e., a correlate of body size), other work has reported that increasing vocal averageness increases attractiveness. Here we investigated the roles these three characteristics play in judgments of the attractiveness of male and female voices. In Study 1, we found that increasing vocal averageness significantly decreased distinctiveness ratings, demonstrating that participants could detect manipulations of vocal averageness in this stimulus set and using this testing paradigm. However, in Study 2, we found no evidence that increasing averageness significantly increased attractiveness ratings of voices. In Study 3, we found that fundamental frequency was negatively correlated with male vocal attractiveness and positively correlated with female vocal attractiveness. By contrast with these results for fundamental frequency, vocal attractiveness and formant frequencies were not significantly correlated. Collectively, our results suggest that averageness may not necessarily significantly increase attractiveness judgments of voices and are consistent with previous work reporting significant associations between attractiveness and voice pitch.

Favorable Antiviral Effect of Metformin on Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of Coronavirus Disease 2019.

BACKGROUND: Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%. METHODS: COVID-OUT was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction. RESULTS: The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95% confidence interval [CI], -1.05 to -.06; P = .027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo. CONCLUSIONS: In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology. CLINICAL TRIALS REGISTRATION: NCT04510194.

Sliding Window INteraction Grammar (SWING): a generalized interaction language model for peptide and protein interactions.

The explosion of sequence data has allowed the rapid growth of protein language models (pLMs). pLMs have now been employed in many frameworks including variant-effect and peptide-specificity prediction. Traditionally, for protein-protein or peptide-protein interactions (PPIs), corresponding sequences are either co-embedded followed by post-hoc integration or the sequences are concatenated prior to embedding. Interestingly, no method utilizes a language representation of the interaction itself. We developed an interaction LM (iLM), which uses a novel language to represent interactions between protein/peptide sequences. S liding W indow In teraction G rammar (SWING) leverages differences in amino acid properties to generate an interaction vocabulary. This vocabulary is the input into a LM followed by a supervised prediction step where the LM's representations are used as features. SWING was first applied to predicting peptide:MHC (pMHC) interactions. SWING was not only successful at generating Class I and Class II models that have comparable prediction to state-of-the-art approaches, but the unique Mixed Class model was also successful at jointly predicting both classes. Further, the SWING model trained only on Class I alleles was predictive for Class II, a complex prediction task not attempted by any existing approach. For de novo data, using only Class I or Class II data, SWING also accurately predicted Class II pMHC interactions in murine models of SLE (MRL/lpr model) and T1D (NOD model), that were validated experimentally. To further evaluate SWING's generalizability, we tested its ability to predict the disruption of specific protein-protein interactions by missense mutations. Although modern methods like AlphaMissense and ESM1b can predict interfaces and variant effects/pathogenicity per mutation, they are unable to predict interaction-specific disruptions. SWING was successful at accurately predicting the impact of both Mendelian mutations and population variants on PPIs. This is the first generalizable approach that can accurately predict interaction-specific disruptions by missense mutations with only sequence information. Overall, SWING is a first-in-class generalizable zero-shot iLM that learns the language of PPIs.

Single-cell transcriptomics reveals evolutionary reconfiguration of embryonic cell fate specification in the sea urchin Heliocidaris erythrogramma.

Altered regulatory interactions during development likely underlie a large fraction of phenotypic diversity within and between species, yet identifying specific evolutionary changes remains challenging. Analysis of single-cell developmental transcriptomes from multiple species provides a powerful framework for unbiased identification of evolutionary changes in developmental mechanisms. Here, we leverage a "natural experiment" in developmental evolution in sea urchins, where a major life history switch recently evolved in the lineage leading to Heliocidaris erythrogramma , precipitating extensive changes in early development. Comparative analyses of scRNA-seq developmental time courses from H. erythrogramma and Lytechinus variegatus (representing the derived and ancestral states respectively) reveals numerous evolutionary changes in embryonic patterning. The earliest cell fate specification events, and the primary signaling center are co-localized in the ancestral dGRN but remarkably, in H. erythrogramma they are spatially and temporally separate. Fate specification and differentiation are delayed in most embryonic cell lineages, although in some cases, these processes are conserved or even accelerated. Comparative analysis of regulator-target gene co-expression is consistent with many specific interactions being preserved but delayed in H. erythrogramma , while some otherwise widely conserved interactions have likely been lost. Finally, specific patterning events are directly correlated with evolutionary changes in larval morphology, suggesting that they are directly tied to the life history shift. Together, these findings demonstrate that comparative scRNA-seq developmental time courses can reveal a diverse set of evolutionary changes in embryonic patterning and provide an efficient way to identify likely candidate regulatory interactions for subsequent experimental validation.

Heart failure in nursing homes: A scoping review of educational interventions for optimising care provision.

Background: Heart failure has an estimated global prevalence of 64.3 million cases, with an average age of a person living with heart failure at 75.2 years. Approximately 20% of residents living in nursing homes (a long-term residential care environment for some individuals) report living with heart failure. Residents living with heart failure in nursing home environments are often frail, have reduced quality of life, higher rates of rehospitalisation and mortality, and greater complications in heart failure management. Further, nursing home staff often lack the knowledge and skills required to provide the necessary care for those living with heart failure. Interventions for improving heart failure management in nursing homes have proven effective, yet there is a lack of understanding regarding interventions for optimising care provision. The aim of this review was to synthesise the current evidence on educational interventions to optimise care provided to people with heart failure in nursing homes. Methods: A scoping review with four databases searched: Medline, CINAHL, Web of Science, and EMBASE. Relevant reference lists were searched manually for additional records. Studies of nursing home staff or resident outcomes associated with changes in care provision (i.e., resident quality of life, staff knowledge of heart failure) were included. Results from the charting data process were collated into themes: intervention outcomes, changes to practice, and implementation and process evaluation. Results: Seven papers were deemed eligible for inclusion. Most studies (n=6) were comprised of nursing home staff only, with one comprised only of residents. Study aims were to improve heart failure knowledge, interprofessional communication, heart failure assessment and management. Positive changes in staff outcomes were observed, with improvements in knowledge, self-efficacy, and confidence in providing care reported. No difference was reported concerning nursing home resident outcomes. Interprofessional communication and staff ability to conduct heart failure assessments improved post-intervention. Changes to practice were mixed, with issues around sustainability reported. Nursing home staff highlighted their appreciation towards receiving education, recommending that videos, images, and humour could improve the intervention content. Conclusions: There is a paucity of evidence around educational interventions to support residents living with heart failure in nursing homes. However, available evidence suggests that educational interventions in nursing homes may improve care through improving staff self-efficacy and confidence in providing care, heart failure knowledge and interprofessional communication. The complexity of implementing educational interventions in the nursing home setting must be considered during the development process to improve implementation, effectiveness, and sustainability.

On the equivalence of scalar-pressure and vector-based acoustic dosage measures as derived from time-limited signal waveformsa).

The dynamic (acoustic pressure) and kinematic (acoustic acceleration and velocity) properties of time-limited signals are studied in terms of acoustic dose metrics as might be used to assess the impact of underwater noise on marine life. The work is relevant for the study of anthropogenic transient acoustic signals, such as airguns, pile driving, and underwater explosive sources, as well as more generic transient signals from sonar systems. Dose metrics are first derived from numerical simulations of sound propagation from a seismic airgun source as specified in a Joint Industry Programme benchmark problem. Similar analyses are carried out based on at-sea acoustic measurements on the continental shelf, made with a vector sensor positioned 1.45 m off the seabed. These measurements are on transient time-limited signals from multiple underwater explosive sources at differing ranges, and from a towed, sonar source. The study demonstrates, both numerically and experimentally, that under many realistic scenarios, kinematic based acoustic dosage metrics within the water column can be evaluated using acoustic pressure measurements.

A step-by-step guide to fragmenting bundled actin filaments.

There has long been conflicting evidence as to how bundled actin filaments, found in cellular structures such as filopodia, are disassembled. In this issue, Chikireddy et al. (https://doi.org/10.1083/jcb.202312106) provide a detailed in vitro analysis of the steps involved in fragmentation of fascin-bundled actin filaments and propose a novel mechanism for severing two-filament bundles.