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Our bringing the heart into balance with the brain in how we choose to treat people at work will lead us to have happier, much more engaged, and productive employees.

American business is losing its war on engagement. As a quick reminder on why we took up arms in the first place, it was June 2013 when Gallup first released its State of The American Workplace study that revealed only 30 percent of the nation's workers were fully engaged in their jobs.

Poly(ethylene terephthalate) (PET) is one of the most abundantly produced synthetic polymers and is accumulating in the environment at a staggering rate as discarded packaging and textiles. The properties that make PET so useful also endow it with an alarming resistance to biodegradation, likely lasting centuries in the environment. Our collective reliance on PET and other plastics means that this buildup will continue unless solutions are found. Recently, a newly discovered bacterium, Ideonella sakaiensis 201-F6, was shown to exhibit the rare ability to grow on PET as a major carbon and energy source. Central to its PET biodegradation capability is a secreted PETase (PET-digesting enzyme). Here, we present a 0.92 Å resolution X-ray crystal structure of PETase, which reveals features common to both cutinases and lipases. PETase retains the ancestral α/β-hydrolase fold but exhibits a more open active-site cleft than homologous cutinases. By narrowing the binding cleft via mutation of two active-site residues to conserved amino acids in cutinases, we surprisingly observe improved PET degradation, suggesting that PETase is not fully optimized for crystalline PET degradation, despite presumably evolving in a PET-rich environment. Additionally, we show that PETase degrades another semiaromatic polyester, polyethylene-2,5-furandicarboxylate (PEF), which is an emerging, bioderived PET replacement with improved barrier properties. In contrast, PETase does not degrade aliphatic polyesters, suggesting that it is generally an aromatic polyesterase. These findings suggest that additional protein engineering to increase PETase performance is realistic and highlight the need for further developments of structure/activity relationships for biodegradation of synthetic polyesters.

Artificial intelligence has been applied in wildfire science and management since the 1990s, with early applications including neural networks and expert systems. Since then, the field has rapidly progressed congruently with the wide adoption of machine learning (ML) methods in the environmental sciences. Here, we present a scoping review of ML applications in wildfire science and management. Our overall objective is to improve awareness of ML methods among wildfire researchers and managers, as well as illustrate the diverse and challenging range of problems in wildfire science available to ML data scientists. To that end, we first present an overview of popular ML approaches used in wildfire science to date and then review the use of ML in wildfire science as broadly categorized into six problem domains, including (i) fuels characterization, fire detection, and mapping; (ii) fire weather and climate change; (iii) fire occurrence, susceptibility, and risk; (iv) fire behavior prediction; (v) fire effects; and (vi) fire management. Furthermore, we discuss the advantages and limitations of various ML approaches relating to data size, computational requirements, generalizability, and interpretability, as well as identify opportunities for future advances in the science and management of wildfires within a data science context. In total, to the end of 2019, we identified 300 relevant publications in which the most frequently used ML methods across problem domains included random forests, MaxEnt, artificial neural networks, decision trees, support vector machines, and genetic algorithms. As such, there exists opportunities to apply more current ML methods — including deep learning and agent-based learning — in the wildfire sciences, especially in instances involving very large multivariate datasets. We must recognize, however, that despite the ability of ML models to learn on their own, expertise in wildfire science is necessary to ensure realistic modelling of fire processes across multiple scales, while the complexity of some ML methods such as deep learning requires a dedicated and sophisticated knowledge of their application. Finally, we stress that the wildfire research and management communities play an active role in providing relevant, high-quality, and freely available wildfire data for use by practitioners of ML methods.

Bats are reservoirs of many zoonotic viruses that are fatal in humans but do not cause disease in bats. Moreover, bats generate low neutralizing antibody titers in response to experimental viral infection, although more robust antibody responses have been observed in wild-caught bats during times of food stress. Here, we compared the antibody titers and B cell receptor (BCR) diversity of Jamaican fruit bats ( Artibeus jamaicensis ; JFBs) and BALB/c mice generated in response to T-dependent and T-independent antigens. We then manipulated the diet of JFBs and challenged them with H18N11 influenza A-like virus or a replication incompetent Nipah virus VSV (Nipah-riVSV). Under standard housing conditions, JFBs generated a lower avidity antibody response and possessed more BCR mRNA diversity compared to BALB/c mice. However, withholding protein from JFBs improved serum neutralization in response to Nipah-riVSV and improved serum antibody titers specific to H18 but reduced BCR mRNA diversity.

The Neoproterozoic was an era of great environmental and biological change, but a paucity of direct and precise age constraints on strata from this time has prevented the complete integration of these records. We present four high-precision U-Pb ages for Neoproterozoic rocks in northwestern Canada that constrain large perturbations in the carbon cycle, a major diversification and depletion in the microfossil record, and the onset of the Sturtian glaciation. A volcanic tuff interbedded with Sturtian glacial deposits, dated at 716.5 million years ago, is synchronous with the age of the Franklin large igneous province and paleomagnetic poles that pin Laurentia to an equatorial position. Ice was therefore grounded below sea level at very low paleolatitudes, which implies that the Sturtian glaciation was global in extent.

In a randomized trial, 1905 patients with left main coronary artery disease were assigned to either percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG). At 5 years, the rates of the composite of death, stroke, or myocardial infarction were not significantly different between the two groups.

ObjectivesSince the onset of the COVID-19 pandemic in 2020, there have been plausible suggestions about the need to augment vitamin D intake by supplementation in order to prevent SARS-CoV2 infection and reduce mortality. Some groups have advocated supplementation for all adults, but governmental agencies have advocated targeted supplementation. We sought to explore the effect of the COVID-19 pandemic on both vitamin D status and on the dose of new-to-market vitamin D supplements.SettingUniversity hospital, Dublin, Ireland.ParticipantsLaboratory-based samples of circulating 25-hydroxyvitamin D (25OHD) (n=100 505).Primary and secondary outcome measuresPrimary outcomes: comparing yearly average 25OHD prior to the pandemic (April 2019 to March 2020) with during the pandemic (April 2020 to March 2021) and comparing the dose of new-to-market vitamin D supplements between 2017 and 2021 (n=2689). Secondary outcome: comparing prevalence of vitamin D deficiency and vitamin D excess during the two time periods.ResultsThe average yearly serum 25OHD measurement increased by 2.8 nmol/L (61.4, 95% CI 61.5 to 61.7 vs 58.6, 95% CI 58.4 to 58.9, p<0.001), which was almost threefold higher than two similar trend analyses that we conducted between 1993 and 2016. There was a lower prevalence of low 25OHD and a higher prevalence of high 25OHD. The dose of new-to-market vitamin D supplements was higher in the years 2020–2021 compared with the years 2017–2019 (p<0.001).ConclusionsWe showed significant increases in serum 25OHD and in the dose of new-to-market vitamin D supplements. The frequency of low vitamin D status reduced indicating benefit, but the frequency of vitamin D excess increased indicating risk of harm. Rather than a blanket recommendation about vitamin D supplementation for all adults, we recommend a targeted approach of supplementation within current governmental guidelines to at-risk groups and cautioning consumers about adverse effects of high dose supplements on the market.

Neoadjuvant use of immune checkpoint inhibitors (ICIs) before liver resection results in pathological tumour regression in patients with hepatocellular carcinoma. We aimed to describe the characteristics of pathological responses after preoperative ICI therapy for hepatocellular carcinoma and to evaluate the association between the depth of tumour regression and relapse-free survival. In this cross-trial, patient-level analysis, we performed a pooled analysis of data from patients with hepatocellular carcinoma receiving ICI therapy before liver resection as part of a global collaborative consortium (NeoHCC) of five phase 1 and 2 clinical trials and standardised observational protocols conducted in 12 tertiary referral centres across the USA, UK, and Taiwan. Eligible patients were adults (aged ≥18 years) diagnosed with hepatocellular carcinoma by tissue core biopsy before treatment initiation, a Liver Imaging Reporting and Data System score of 5 on imaging, or both, with an Eastern Cooperative Oncology Group performance status score of 0–1, and no extrahepatic spread or previous ICI treatment. Pathological response was measured as the percentage of non-viable tumour in the resected surgical specimen, with major pathological response corresponding to at least 70% tumour regression and pathological complete response corresponding to 100% tumour regression. We correlated pathological response with radiological overall response using RECIST criteria (version 1.1) and relapse-free survival, and evaluated the threshold of tumour regression that could be optimally associated with relapse-free survival. At data cutoff on Jan 31, 2024, 111 patients were included in the study, of whom data on pathological response were available for 104 (94%) patients. Patients received treatment from Oct 5, 2017, to Nov 15, 2023, mostly ICI combinations (76 [69%]), for a median of 1·4 months (IQR 0·7–2·9). 87 (78%) patients were men and 24 (22%) were women. Most patients had underlying viral chronic liver disease (73 [66%]) and Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma (61 [55%]), without portal vein thrombosis (87 [78%]). We observed major pathological response in 33 (32%) patients and pathological complete response in 19 (18%) patients. Radiological overall response was associated with major pathological response, with 23 (74%) of 31 patients with radiological response showing major pathological response compared with ten (14%) of 73 patients without radiological response (p<0·0001). However, ten (30%) of 33 major pathological responses were not predicted by radiological response. After a median follow-up of 27·2 months (95% CI 22·3–32·1), median relapse-free survival for the whole cohort was 43·6 months (95% CI 28·3–not evaluable). Relapse-free survival was significantly longer in patients with major pathological response than in those who did not have a major pathological response (not reached [95% CI not evaluable–not evaluable] vs 28·3 months [12·8–43·8]; hazard ratio 0·26 [0·10–0·66]; p=0·0024) and in patients with pathological complete response than in those who did not have a pathological complete response (NR [95% CI not evaluable–not evaluable] vs 32·8 months [15·0–50·5]; 0·19 [0·05–0·78]; p=0·010). Unbiased recursive partitioning of the cohort for the risk of relapse, death, or both identified a threshold of 90% as the optimal cutoff of pathological tumour regression to predict improved relapse-free survival. The extent of tumour regression following neoadjuvant ICI therapy could identify patients with improved relapse-free survival following liver resection. The threshold of at least 90% tumour regression should be validated for its surrogate role for relapse-free survival in phase 3 randomised controlled trials. None.