mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron.

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.

Wave-like dopamine dynamics as a mechanism for spatiotemporal credit assignment.

Significant evidence supports the view that dopamine shapes learning by encoding reward prediction errors. However, it is unknown whether striatal targets receive tailored dopamine dynamics based on regional functional specialization. Here, we report wave-like spatiotemporal activity patterns in dopamine axons and release across the dorsal striatum. These waves switch between activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. Notably, wave trajectories were tailored to task demands, propagating from dorsomedial to dorsolateral striatum when rewards are contingent on animal behavior and in the opponent direction when rewards are independent of behavioral responses. We propose a computational architecture in which striatal dopamine waves are sculpted by inference about agency and provide a mechanism to direct credit assignment to specialized striatal subregions. Supporting model predictions, dorsomedial dopamine activity during reward-pursuit signaled the extent of instrumental control and interacted with reward waves to predict future behavioral adjustments.

Substrate-dependent effects of quaternary structure on RNase E activity.

RNase E is an essential, multifunctional ribonuclease encoded in E. coli by the rne gene. Structural analysis indicates that the ribonucleolytic activity of this enzyme is conferred by rne-encoded polypeptide chains that (1) dimerize to form a catalytic site at the protein-protein interface, and (2) multimerize further to generate a tetrameric quaternary structure consisting of two dimerized Rne-peptide chains. We identify here a mutation in the Rne protein's catalytic region (E429G), as well as a bacterial cell wall peptidoglycan hydrolase (Amidase C [AmiC]), that selectively affect the specific activity of the RNase E enzyme on long RNA substrates, but not on short synthetic oligonucleotides, by enhancing enzyme multimerization. Unlike the increase in specific activity that accompanies concentration-induced multimerization, enhanced multimerization associated with either the E429G mutation or interaction of the Rne protein with AmiC is independent of the substrate's 5' terminus phosphorylation state. Our findings reveal a previously unsuspected substrate length-dependent regulatory role for RNase E quaternary structure and identify cis-acting and trans-acting factors that mediate such regulation.

A kilonova following a long-duration gamma-ray burst at 350 Mpc.

Gamma-ray bursts (GRBs) are divided into two populations1,2; long GRBs that derive from the core collapse of massive stars (for example, ref. 3) and short GRBs that form in the merger of two compact objects4,5. Although it is common to divide the two populations at a gamma-ray duration of 2 s, classification based on duration does not always map to the progenitor. Notably, GRBs with short (≲2 s) spikes of prompt gamma-ray emission followed by prolonged, spectrally softer extended emission (EE-SGRBs) have been suggested to arise from compact object mergers6-8. Compact object mergers are of great astrophysical importance as the only confirmed site of rapid neutron capture (r-process) nucleosynthesis, observed in the form of so-called kilonovae9-14. Here we report the discovery of a possible kilonova associated with the nearby (350 Mpc), minute-duration GRB 211211A. The kilonova implies that the progenitor is a compact object merger, suggesting that GRBs with long, complex light curves can be spawned from merger events. The kilonova of GRB 211211A has a similar luminosity, duration and colour to that which accompanied the gravitational wave (GW)-detected binary neutron star (BNS) merger GW170817 (ref. 4). Further searches for GW signals coincident with long GRBs are a promising route for future multi-messenger astronomy.

Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL.

The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. Our study implicates five networks of kinases that regulate the switch to polyploidy. Moreover, we find that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. An integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora kinase A (AURKA). We further find that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL activity in vivo. Our findings provide a rationale to support clinical trials of MLN8237 and other inducers of polyploidization and differentiation in AMKL.

Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA.

The immunosuppressive protein PD-L1 is upregulated in many cancers and contributes to evasion of the host immune system. The relative importance of the tumor microenvironment and cancer cell-intrinsic signaling in the regulation of PD-L1 expression remains unclear. We report that oncogenic RAS signaling can upregulate tumor cell PD-L1 expression through a mechanism involving increases in PD-L1 mRNA stability via modulation of the AU-rich element-binding protein tristetraprolin (TTP). TTP negatively regulates PD-L1 expression through AU-rich elements in the 3' UTR of PD-L1 mRNA. MEK signaling downstream of RAS leads to phosphorylation and inhibition of TTP by the kinase MK2. In human lung and colorectal tumors, RAS pathway activation is associated with elevated PD-L1 expression. In vivo, restoration of TTP expression enhances anti-tumor immunity dependent on degradation of PD-L1 mRNA. We demonstrate that RAS can drive cell-intrinsic PD-L1 expression, thus presenting therapeutic opportunities to reverse the innately immunoresistant phenotype of RAS mutant cancers.

Neocortical interneurons: from diversity, strength.

Interneurons in the neocortex of the brain are small, locally projecting inhibitory GABAergic cells with a broad array of anatomical and physiological properties. The diversity of interneurons is believed to be crucial for regulating myriad operations in the neocortex. Here, we describe current theories about how interneuron diversity may support distinct neocortical processes that underlie perception.

Expanded MutaT7 toolkit efficiently and simultaneously accesses all possible transition mutations in bacteria.

Targeted mutagenesis mediated by nucleotide base deaminase-T7 RNA polymerase fusions has recently emerged as a novel and broadly useful strategy to power genetic diversification in the context of in vivo directed evolution campaigns. Here, we expand the utility of this approach by introducing a highly active adenosine deaminase-T7 RNA polymerase fusion protein (eMutaT7A→G), resulting in higher mutation frequencies to enable more rapid directed evolution. We also assess the benefits and potential downsides of using this more active mutator. We go on to show in Escherichia coli that adenosine deaminase-bearing mutators (MutaT7A→G or eMutaT7A→G) can be employed in tandem with a cytidine deaminase-bearing mutator (MutaT7C→T) to introduce all possible transition mutations simultaneously. We illustrate the efficacy of this in vivo mutagenesis approach by exploring mutational routes to antibacterial drug resistance. This work sets the stage for general application of optimized MutaT7 tools able to induce all types of transition mutations during in vivo directed evolution campaigns across diverse organisms.

Pathophysiological Responses to Bloodstream Infection in Critically Ill Transplant Recipients Compared With Non-Transplant Recipients.

BACKGROUND: Identification of bloodstream infection (BSI) in transplant recipients may be difficult due to immunosuppression. Accordingly, we aimed to compare responses to BSI in critically ill transplant and non-transplant recipients and to modify systemic inflammatory response syndrome (SIRS) criteria for transplant recipients. METHODS: We analyzed univariate risks and developed multivariable models of BSI with 27 clinical variables from adult intensive care unit (ICU) patients at the University of Virginia (UVA) and at the University of Pittsburgh (Pitt). We used Bayesian inference to adjust SIRS criteria for transplant recipients. RESULTS: We analyzed 38.7 million hourly measurements from 41 725 patients at UVA, including 1897 transplant recipients with 193 episodes of BSI and 53 608 patients at Pitt, including 1614 transplant recipients with 768 episodes of BSI. The univariate responses to BSI were comparable in transplant and non-transplant recipients. The area under the receiver operating characteristic curve (AUC) was 0.82 (95% confidence interval [CI], .80-.83) for the model using all UVA patient data and 0.80 (95% CI, .76-.83) when using only transplant recipient data. The UVA all-patient model had an AUC of 0.77 (95% CI, .76-.79) in non-transplant recipients and 0.75 (95% CI, .71-.79) in transplant recipients at Pitt. The relative importance of the 27 predictors was similar in transplant and non-transplant models. An upper temperature of 37.5°C in SIRS criteria improved reclassification performance in transplant recipients. CONCLUSIONS: Critically ill transplant and non-transplant recipients had similar responses to BSI. An upper temperature of 37.5°C in SIRS criteria improved BSI screening in transplant recipients.

Antimalarial resistance risk in Mozambique detected by a novel quadruplex droplet digital PCR assay.

While the Plasmodium falciparum malaria parasite continues to cause severe disease globally, Mozambique is disproportionally represented in malaria case totals. Acquisition of copy number variations (CNVs) in the parasite genome contributes to antimalarial drug resistance through overexpression of drug targets. Of interest, piperaquine resistance is associated with plasmepsin 2 and 3 CNVs (pfpmp2 and pfpmp3, respectively), while CNVs in the multidrug efflux pump, multidrug resistance-1 (pfmdr1), increase resistance to amodiaquine and lumefantrine. These antimalarials are partner drugs in artemisinin combination therapies (ACTs) and therefore, CNV detection with accurate and efficient tools is necessary to track ACT resistance risk. Here, we evaluated ~300 clinically derived samples collected from three sites in Mozambique for resistance-associated CNVs. We developed a novel, medium-throughput, quadruplex droplet digital PCR (ddPCR) assay to simultaneously quantify the copy number of pfpmp3, pfpmp2, and pfmdr1 loci in these clinical samples. By using DNA from laboratory parasite lines, we show that this nanodroplet-based method is capable of detecting picogram levels of parasite DNA, which facilitates its application for low yield and human host-contaminated clinical surveillance samples. Following ddPCR and the application of quality control standards, we detected CNVs in 13 of 229 high-quality samples (prevalence of 5.7%). Overall, our study revealed a low number of resistance CNVs present in the parasite population across all three collection sites, including various combinations of pfmdr1, pfpmp2, and pfpmp3 CNVs. The potential for future ACT resistance across Mozambique emphasizes the need for continued molecular surveillance across the region.

Mutualisms in a warming world.

Predicting the impacts of global warming on mutualisms poses a significant challenge given the functional and life history differences that usually exist among interacting species. However, this is a critical endeavour since virtually all species on Earth depend on other species for survival and/or reproduction. The field of thermal ecology can provide physiological and mechanistic insights, as well as quantitative tools, for addressing this challenge. Here, we develop a conceptual and quantitative framework that connects thermal physiology to species' traits, species' traits to interacting mutualists' traits and interacting traits to the mutualism. We first identify the functioning of reciprocal mutualism-relevant traits in diverse systems as the key temperature-dependent mechanisms driving the interaction. We then develop metrics that measure the thermal performance of interacting mutualists' traits and that approximate the thermal performance of the mutualism itself. This integrated approach allows us to additionally examine how warming might interact with resource/nutrient availability and affect mutualistic species' associations across space and time. We offer this framework as a synthesis of convergent and critical issues in mutualism science in a changing world, and as a baseline to which other ecological complexities and scales might be added.

Cadence (steps/min) and relative intensity in 61 to 85-year-olds: the CADENCE-Adults study.

BACKGROUND: We previously demonstrated that a heuristic (i.e., evidence-based, rounded yet practical) cadence threshold of ≥ 100 steps/min was associated with absolutely-defined moderate intensity physical activity (i.e., ≥ 3 metabolic equivalents [METs]) in older adults 61-85 years of age. Although it was difficult to ascertain achievement of absolutely-defined vigorous (6 METs) intensity, ≥ 130 steps/min was identified as a defensible threshold for this population. However, little evidence exists regarding cadence thresholds and relatively-defined moderate intensity indicators, including ≥ 64% heart rate [HR] maximum [HRmax = 220-age], ≥ 40% HR reserve [HRR = HRmax-HRresting], and ≥ 12 Borg Scale Rating of Perceived Exertion [RPE]; or vigorous intensity indicators including ≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE. PURPOSE: To analyze the relationship between cadence and relatively-defined physical activity intensity and identify relatively-defined moderate and vigorous heuristic cadence thresholds for older adults 61-85 years of age. METHODS: Ninety-seven ostensibly healthy adults (72.7 ± 6.9 years; 49.5% women) completed up to nine 5-min treadmill walking bouts beginning at 0.5 mph (0.8 km/h) and progressing by 0.5 mph speed increments (with 2-min rest between bouts). Directly-observed (and video-recorded) steps were hand-counted, HR was measured using a chest-strapped monitor, and in the final minute of each bout, participants self-reported RPE. Segmented mixed model regression and Receiver Operating Characteristic (ROC) curve analyses identified optimal cadence thresholds associated with relatively-defined moderate (≥ 64%HRmax, ≥ 40%HRR, and ≥ 12 RPE) and vigorous (≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE) intensities. A compromise between the two analytical methods, including Youden's Index (a sum of sensitivity and specificity), positive and negative predictive values, and overall accuracy, yielded final heuristic cadences. RESULTS: Across all relatively-defined moderate intensity indicators, segmented regression models and ROC curve analyses identified optimal cadence thresholds ranging from 105.9 to 112.8 steps/min and 102.0-104.3 steps/min, respectively. Comparable values for vigorous intensity indicators ranged between126.1-132.1 steps/min and 106.7-116.0 steps/min, respectively. Regardless of the relatively-defined intensity indicator, the overall best heuristic cadence threshold aligned with moderate intensity was ≥ 105 steps/min. Vigorous intensity varied between ≥ 115 (greater sensitivity) or ≥ 120 (greater specificity) steps/min. CONCLUSIONS: Heuristic cadence thresholds align with relatively-defined intensity indicators and can be useful for studying and prescribing older adults' physiological response to, and/or perceived experience of, ambulatory physical activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

Parasites indicate trophic complexity and faunal succession in restored oyster reefs over a 22-year period.

Foundation species like the eastern oyster (Crassostrea virginica) create complex habitats for organisms across multiple trophic levels. Historic declines in oyster abundance have prompted decades of restoration efforts. However, it remains unclear how long it takes for restored reefs to resemble the trophic complexity of natural reefs. We used a space-for-time approach to examine community succession of restored reefs ranging in age from 3 to 22 years old in coastal North Carolina, surveying both free-living taxa and parasite communities and comparing them to natural reefs that are decades old. Trophically transmitted parasites can serve as valuable biodiversity surrogates, sometimes providing greater information about a system or question than their free-living counterparts. We found that the diversity of free-living taxa was highly variable and did not differ among new (<10 years), old (20 years), and natural reefs. Conversely, parasite diversity increased with elapsed time after restoration, and parasite communities in older restored reefs resembled those found in natural reefs. Our study also revealed that oyster toadfish (Opsanus tau) act as a key host species capable of facilitating parasite transmission and trophic ascent in oyster reef food webs. Overall, our results suggest that trophic complexity in restored oyster reefs requires at least 8 years to resemble that found in natural reefs. This work adds to a growing body of evidence demonstrating how parasites can serve as biodiversity surrogates, proxies for the presence of additional taxa that are often difficult or impractical to sample. Given the multiplicity of links formed with their hosts, parasites offer a powerful tool for quantifying diversity and trophic complexity in environmental monitoring studies.

Tundra uptake of atmospheric elemental mercury drives Arctic mercury pollution.

Anthropogenic activities have led to large-scale mercury (Hg) pollution in the Arctic. It has been suggested that sea-salt-induced chemical cycling of Hg (through 'atmospheric mercury depletion events', or AMDEs) and wet deposition via precipitation are sources of Hg to the Arctic in its oxidized form (Hg(ii)). However, there is little evidence for the occurrence of AMDEs outside of coastal regions, and their importance to net Hg deposition has been questioned. Furthermore, wet-deposition measurements in the Arctic showed some of the lowest levels of Hg deposition via precipitation worldwide, raising questions as to the sources of high Arctic Hg loading. Here we present a comprehensive Hg-deposition mass-balance study, and show that most of the Hg (about 70%) in the interior Arctic tundra is derived from gaseous elemental Hg (Hg(0)) deposition, with only minor contributions from the deposition of Hg(ii) via precipitation or AMDEs. We find that deposition of Hg(0)-the form ubiquitously present in the global atmosphere-occurs throughout the year, and that it is enhanced in summer through the uptake of Hg(0) by vegetation. Tundra uptake of gaseous Hg(0) leads to high soil Hg concentrations, with Hg masses greatly exceeding the levels found in temperate soils. Our concurrent Hg stable isotope measurements in the atmosphere, snowpack, vegetation and soils support our finding that Hg(0) dominates as a source to the tundra. Hg concentration and stable isotope data from an inland-to-coastal transect show high soil Hg concentrations consistently derived from Hg(0), suggesting that the Arctic tundra might be a globally important Hg sink. We suggest that the high tundra soil Hg concentrations might also explain why Arctic rivers annually transport large amounts of Hg to the Arctic Ocean.

Thalamocortical Mechanisms Regulating the Relationship between Transient Beta Events and Human Tactile Perception.

Transient neocortical events with high spectral power in the 15-29 Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100-300 ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, nonlemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300 ms timescale to suppress sensory information. Further analysis showed that the same beta-generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The postevent suppressive mechanism explains an array of studies that associate beta with decreased processing, whereas the during-event facilitatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.

Cadence-based classification of moderate-intensity overground walking in 41- to 85-year-old adults.

BACKGROUND: Walking cadence (steps/min) has emerged as a valid proxy of physical activity intensity, with consensus across numerous laboratory-based treadmill studies that ≥100 steps/min approximates absolutely defined moderate intensity (≥3 metabolic equivalents; METs). We recently reported that this cadence threshold had a classification accuracy of 73.3% for identifying moderate intensity during preferred pace overground walking in young adults. The purpose of this study was to evaluate and compare the performance of a cadence threshold of ≥100 steps/min for correctly classifying moderate intensity during overground walking in middle- and older-aged adults. METHODS: Participants (N = 174, 48.3% female, 41-85 years of age) completed laboratory-based cross-sectional study involving an indoor 5-min overground walking trial at their preferred pace. Steps were manually counted and converted to cadence (total steps/5 min). Intensity was measured using indirect calorimetry and expressed as METs. Classification accuracy (sensitivity, specificity, accuracy) of a cadence threshold of ≥100 steps/min to identify individuals walking at ≥3 METs was calculated. RESULTS: The ≥100 steps/min threshold demonstrated accuracy of 74.7% for classifying moderate intensity. When comparing middle- vs. older-aged adults, similar accuracy (73.4% vs. 75.8%, respectively) and specificity (33.3% vs. 34.5%) were observed. Sensitivity was high, but was lower for middle- vs. older-aged adults (85.2% vs. 93.9%, respectively). CONCLUSION: A cadence threshold of ≥100 steps/min accurately identified moderate-intensity overground walking. Furthermore, accuracy was similar when comparing middle- and older-aged adults. These findings extend our previous analysis in younger adults and confirm the appropriateness of applying this cadence threshold across the adult lifespan.

A scoping review on the impact of the COVID-19 pandemic on physical activity and sedentary behavior in Saudi Arabia.

BACKGROUND: In Saudi Arabia, stay-at-home orders to address the coronavirus disease 2019 (COVID-19) pandemic between March 15 and 23, 2020 and eased on May 28, 2020. We conducted a scoping review to systematically describe physical activity and sedentary behavior in Saudi Arabia associated with the timing of the lockdown. METHODS: We searched six databases on December 13, 2021 for articles published in English or Arabic from 2018 to the search date. Studies must have reported data from Saudi Arabia for any age and measured physical activity or sedentary behavior. RESULTS: Overall, 286 records were found; after excluding duplicates, 209 records were screened, and 19 studies were included in the review. Overall, 15 studies were cross-sectional, and 4 studies were prospective cohorts. Three studies included children and adolescents (age: 2-18 years), and 16 studies included adults (age: 15-99 years). Data collection periods were < = 5 months, with 17 studies collecting data in 2020 only, one study in 2020-2021, and one study in 2021. The median analytic sample size was 363 (interquartile range 262-640). Three studies of children/adolescents collected behaviors online at one time using parental reporting, with one also allowing self-reporting. All three studies found that physical activity was lower during and/or following the lockdown than before the lockdown. Two studies found screen time, television watching, and playing video games were higher during or following the lockdown than before the lockdown. Sixteen adult studies assessed physical activity, with 15 utilizing self-reporting and one using accelerometry. Physical activity, exercise, walking, and park visits were all lower during or following the lockdown than before the lockdown. Six adult studies assessed sedentary behavior using self-report. Sitting time (4 studies) and screen time (2 studies) were higher during or following the lockdown than before the lockdown. CONCLUSIONS: Among children, adolescents, and adults, studies consistently indicated that in the short-term, physical activity decreased and sedentary behavior increased in conjunction with the movement restrictions. Given the widespread impact of the pandemic on other health behaviors, it would be important to continue tracking behaviors post-lockdown and identify subpopulations that may not have returned to their physical activity and sedentary behavior to pre-pandemic levels to focus on intervention efforts.

Emergency Department Point-of-Care Echocardiography and Lung Ultrasound in Predicting COVID-19 Severity.

OBJECTIVES: We sought to determine if point-of-care ultrasound (POCUS) performed on patients with COVID-19 in the emergency department (ED) can help predict disease course, severity, or identify complications. METHODS: This was a retrospective cohort study of adult ED patients who tested positive for COVID-19 at hospital admission or within 2 weeks of presentation and received heart or lung POCUS. Clips were reviewed for presence of decreased left ventricular ejection fraction (LVEF), right ventricular dilation, presence of B-lines, and pleural line abnormalities. Patients with worsening hypoxemic respiratory failure or shock requiring higher level of care and patients who expired were considered to have developed severe COVID-19. Regression analysis was performed to determine if there was a correlation between ED POCUS findings and development of severe COVID-19. RESULTS: A total of 155 patients met study criteria; 148 patients had documented cardiac views and 116 patients had documented lung views (113 with both). Mean age was 66.5 years old (±18.6) and 53% of subjects were female. Subjects with decreased LVEF that was not previously documented had increased odds of having severe COVID during their hospitalization compared to those with old or no dysfunction (OR 5.66, 95% CI: 1.55-19.95, P = .08). The presence of pleural line abnormalities was also predictive for development of severe COVID (OR 2.68, 95% CI: 1.04-6.92, P = .04). CONCLUSION: POCUS findings of previously unidentified decreased LVEF and pleural line abnormalities in patients with COVID-19 evaluated in the ED were correlated to a more severe clinical course and worse prognosis.

Continuous ECG monitoring should be the heart of bedside AI-based predictive analytics monitoring for early detection of clinical deterioration.

The idea that we can detect subacute potentially catastrophic illness earlier by using statistical models trained on clinical data is now well-established. We review evidence that supports the role of continuous cardiorespiratory monitoring in these predictive analytics monitoring tools. In particular, we review how continuous ECG monitoring reflects the patient and not the clinician, is less likely to be biased, is unaffected by changes in practice patterns, captures signatures of illnesses that are interpretable by clinicians, and is an underappreciated and underutilized source of detailed information for new mathematical methods to reveal.

The Impact of Real-Time Whole-Genome Sequencing in Controlling Healthcare-Associated SARS-CoV-2 Outbreaks.

Nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have severely affected bed capacity and patient flow. We utilized whole-genome sequencing (WGS) to identify outbreaks and focus infection control resources and intervention during the United Kingdom's second pandemic wave in late 2020. Phylogenetic analysis of WGS and epidemiological data pinpointed an initial transmission event to an admission ward, with immediate prior community infection linkage documented. High incidence of asymptomatic staff infection with genetically identical viral sequences was also observed, which may have contributed to the propagation of the outbreak. WGS allowed timely nosocomial transmission intervention measures, including admissions ward point-of-care testing and introduction of portable HEPA14 filters. Conversely, WGS excluded nosocomial transmission in 2 instances with temporospatial linkage, conserving time and resources. In summary, WGS significantly enhanced understanding of SARS-CoV-2 clusters in a hospital setting, both identifying high-risk areas and conversely validating existing control measures in other units, maintaining clinical service overall.