Circulation of multidrug-resistant bacteria (MRB) in healthcare facilities is a major public health problem. These settings have been greatly impacted by the Coronavirus Disease 2019 (COVID-19) ...pandemic, notably due to surges in COVID-19 caseloads and the implementation of infection control measures. We sought to evaluate how such collateral impacts of COVID-19 impacted the nosocomial spread of MRB in an early pandemic context.
We developed a mathematical model in which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and MRB cocirculate among patients and staff in a theoretical hospital population. Responses to COVID-19 were captured mechanistically via a range of parameters that reflect impacts of SARS-CoV-2 outbreaks on factors relevant for pathogen transmission. COVID-19 responses include both "policy responses" willingly enacted to limit SARS-CoV-2 transmission (e.g., universal masking, patient lockdown, and reinforced hand hygiene) and "caseload responses" unwillingly resulting from surges in COVID-19 caseloads (e.g., abandonment of antibiotic stewardship, disorganization of infection control programmes, and extended length of stay for COVID-19 patients). We conducted 2 main sets of model simulations, in which we quantified impacts of SARS-CoV-2 outbreaks on MRB colonization incidence and antibiotic resistance rates (the share of colonization due to antibiotic-resistant versus antibiotic-sensitive strains). The first set of simulations represents diverse MRB and nosocomial environments, accounting for high levels of heterogeneity across bacterial parameters (e.g., rates of transmission, antibiotic sensitivity, and colonization prevalence among newly admitted patients) and hospital parameters (e.g., rates of interindividual contact, antibiotic exposure, and patient admission/discharge). On average, COVID-19 control policies coincided with MRB prevention, including 28.2% 95% uncertainty interval: 2.5%, 60.2% fewer incident cases of patient MRB colonization. Conversely, surges in COVID-19 caseloads favoured MRB transmission, resulting in a 13.8% -3.5%, 77.0% increase in colonization incidence and a 10.4% 0.2%, 46.9% increase in antibiotic resistance rates in the absence of concomitant COVID-19 control policies. When COVID-19 policy responses and caseload responses were combined, MRB colonization incidence decreased by 24.2% -7.8%, 59.3%, while resistance rates increased by 2.9% -5.4%, 23.2%. Impacts of COVID-19 responses varied across patients and staff and their respective routes of pathogen acquisition. The second set of simulations was tailored to specific hospital wards and nosocomial bacteria (methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli). Consequences of nosocomial SARS-CoV-2 outbreaks were found to be highly context specific, with impacts depending on the specific ward and bacteria evaluated. In particular, SARS-CoV-2 outbreaks significantly impacted patient MRB colonization only in settings with high underlying risk of bacterial transmission. Yet across settings and species, antibiotic resistance burden was reduced in facilities with timelier implementation of effective COVID-19 control policies.
Our model suggests that surges in nosocomial SARS-CoV-2 transmission generate selection for the spread of antibiotic-resistant bacteria. Timely implementation of efficient COVID-19 control measures thus has 2-fold benefits, preventing the transmission of both SARS-CoV-2 and MRB, and highlighting antibiotic resistance control as a collateral benefit of pandemic preparedness.
An ecosystem approach is widely seen as a desirable goal for fisheries management but there is little consensus on what strategies or measures are needed to achieve it. Management strategy evaluation ...(MSE) is a tool that has been widely used to develop and test single species fisheries management strategies and is now being extended to support ecosystem based fisheries management (EBFM). We describe the application of MSE to investigate alternative strategies for achieving EBFM goals for a complex multispecies fishery in southeastern Australia. The study was undertaken as part of a stakeholder driven process to review and improve the ecological, economic and social performance of the fishery. An integrated management strategy, involving combinations of measures including quotas, gear controls and spatial management, performed best against a wide range of objectives and this strategy was subsequently adopted in the fishery, leading to marked improvements in performance. Although particular to one fishery, the conclusion that an integrated package of measures outperforms single focus measures we argue is likely to apply widely in fisheries that aim to achieve EBFM goals.
Invisibility is a notion that has long captivated the popular imagination. However, in 2006, invisibility became a practical matter for the scientific community as well, with the suggestion that ...artificially structured metamaterials could enable a new electromagnetic design paradigm, now termed transformation optics. Since the advent of transformation optics and subsequent initial demonstration of the microwave cloak, the field has grown rapidly. However, the complexity of the transformation optics material prescription has continually forced researchers to make simplifying approximations to achieve even a subset of the desired functionality. These approximations place profound limitations on the performance of transformation optics devices in general, and cloaks especially. Here, we design and experimentally characterize a two-dimensional, unidirectional cloak that makes no approximations to the underlying transformation optics formulation, yet is capable of reducing the scattering of an object ten wavelengths in size. We demonstrate that this approximation-free design regains the performance characteristics promised by transformation optics.
Ultrathin dielectric gaps between metals can trap plasmonic optical modes with surprisingly low loss and with volumes below 1 nm
. We review the origin and subtle properties of these modes, and show ...how they can be well accounted for by simple models. Particularly important is the mixing between radiating antennas and confined nanogap modes, which is extremely sensitive to precise nanogeometry, right down to the single-atom level. Coupling nanogap plasmons to electronic and vibronic transitions yields a host of phenomena including single-molecule strong coupling and molecular optomechanics, opening access to atomic-scale chemistry and materials science, as well as quantum metamaterials. Ultimate low-energy devices such as robust bottom-up assembled single-atom switches are thus in prospect.
Summary Background The intensity, spread, and effects of public opinion about vaccines are growing as new modes of communication speed up information sharing, contributing to vaccine hesitancy, ...refusals, and disease outbreaks. We aimed to develop a new application of existing surveillance systems to detect and characterise early signs of vaccine issues. We also aimed to develop a typology of concerns and a way to assess the priority of each concern. Methods Following preliminary research by The Vaccine Confidence Project, media reports (eg, online articles, blogs, government reports) were obtained using the HealthMap automated data collection system, adapted to monitor online reports about vaccines, vaccination programmes, and vaccine-preventable diseases. Any reports that did not meet the inclusion criteria—any reference to a human vaccine or vaccination campaign or programme that was accessible online—were removed from analysis. Reports were manually analysed for content and categorised by concerns, vaccine, disease, location, and source of report, and overall positive or negative sentiment towards vaccines. They were then given a priority level depending on the seriousness of the reported event and time of event occurrence. We used descriptive statistics to analyse the data collected during a period of 1 year, after refinements to the search terms and processes had been made. Findings We analysed data from 10 380 reports (from 144 countries) obtained between May 1, 2011, and April 30, 2012. 7171 (69%) contained positive or neutral content and 3209 (31%) contained negative content. Of the negative reports, 1977 (24%) were associated with impacts on vaccine programmes and disease outbreaks; 1726 (21%) with beliefs, awareness, and perceptions; 1371 (16%) with vaccine safety; and 1336 (16%) with vaccine delivery programmes. We were able to disaggregate the data by country and vaccine type, and monitor evolution of events over time and location in specific regions where vaccine concerns were high. Interpretation Real-time monitoring and analysis of vaccine concerns over time and location could help immunisation programmes to tailor more effective and timely strategies to address specific public concerns. Funding Bill & Melinda Gates Foundation.
Neo-sex chromosomes are found in many taxa, but the forces driving their emergence and spread are poorly understood. The female-specific neo-W chromosome of the African monarch (or queen) butterfly ...Danaus chrysippus presents an intriguing case study because it is restricted to a single 'contact zone' population, involves a putative colour patterning supergene, and co-occurs with infection by the male-killing endosymbiont Spiroplasma. We investigated the origin and evolution of this system using whole genome sequencing. We first identify the 'BC supergene', a broad region of suppressed recombination across nearly half a chromosome, which links two colour patterning loci. Association analysis suggests that the genes yellow and arrow in this region control the forewing colour pattern differences between D. chrysippus subspecies. We then show that the same chromosome has recently formed a neo-W that has spread through the contact zone within approximately 2,200 years. We also assembled the genome of the male-killing Spiroplasma, and find that it shows perfect genealogical congruence with the neo-W, suggesting that the neo-W has hitchhiked to high frequency as the male-killer has spread through the population. The complete absence of female crossing-over in the Lepidoptera causes whole-chromosome hitchhiking of a single neo-W haplotype, carrying a single allele of the BC supergene and dragging multiple non-synonymous mutations to high frequency. This has created a population of infected females that all carry the same recessive colour patterning allele, making the phenotypes of each successive generation highly dependent on uninfected male immigrants. Our findings show how hitchhiking can occur between the physically unlinked genomes of host and endosymbiont, with dramatic consequences.
FoundationOne®CDx (F1CDx) is a United States (US) Food and Drug Administration (FDA)-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the ...approved therapeutic product labeling for 28 drug therapies. F1CDx utilizes next-generation sequencing (NGS)-based comprehensive genomic profiling (CGP) technology to examine 324 cancer genes in solid tumors. F1CDx reports known and likely pathogenic short variants (SVs), copy number alterations (CNAs), and select rearrangements, as well as complex biomarkers including tumor mutational burden (TMB) and microsatellite instability (MSI), in addition to genomic loss of heterozygosity (gLOH) in ovarian cancer. CGP services can reduce the complexity of biomarker testing, enabling precision medicine to improve treatment decision-making and outcomes for cancer patients, but only if test results are reliable, accurate, and validated clinically and analytically to the highest standard available. The analyses presented herein demonstrate the extensive analytical and clinical validation supporting the F1CDx initial and subsequent FDA approvals to ensure high sensitivity, specificity, and reliability of the data reported. The analytical validation included several in-depth evaluations of F1CDx assay performance including limit of detection (LoD), limit of blank (LoB), precision, and orthogonal concordance for SVs (including base substitutions SUBs and insertions/deletions INDELs), CNAs (including amplifications and homozygous deletions), genomic rearrangements, and select complex biomarkers. The assay validation of >30,000 test results comprises a considerable and increasing body of evidence that supports the clinical utility of F1CDx to match patients with solid tumors to targeted therapies or immunotherapies based on their tumor's genomic alterations and biomarkers. F1CDx meets the clinical needs of providers and patients to receive guideline-based biomarker testing, helping them keep pace with a rapidly evolving field of medicine.
Cattle with subclinical endometritis (SCE) are sub-fertile and diagnosing subclinical uterine disease remains a challenge. The hypothesis for this study was that endometrial inflammation is reflected ...in mRNA expression patterns of peripheral blood leucocytes. Transcriptome profiles were evaluated in healthy cows and in cows with SCE using circulating white blood cells (WBC) and endometrial biopsy samples collected from the same animals at 45-55 days postpartum. Bioinformatic analyses of microarray-based transcriptional data identified gene profiles associated with distinct biological functions in circulating WBC and endometrium. In circulating WBC, SCE promotes a pro-inflammatory environment, whereas functions related to tissue remodeling are also affected in the endometrium. Nineteen differentially expressed genes associated with SCE were common to both circulating WBC and the endometrium. Among these genes, transcript abundance of immune factors C3, C2, LTF, PF4 and TRAPPC13 were up-regulated in SCE cows at 45-55 days postpartum. Moreover, mRNA expression of C3, CXCL8, LTF, TLR2 and TRAPPC13 was temporally regulated during the postpartum period in circulating WBC of healthy cows compared with SCE cows. This observation might indicate an advantageous modulation of the immune system in healthy animals. The transcript abundance of these genes represents a potential source of indicators for postpartum uterine health.
Protein accumulation and aggregation with a concomitant loss of proteostasis often contribute to neurodegenerative diseases, and the ubiquitin-proteasome system plays a major role in protein ...degradation and proteostasis. Here, we show that three different proteins from Alzheimer's, Parkinson's, and Huntington's disease that misfold and oligomerize into a shared three-dimensional structure potently impair the proteasome. This study indicates that the shared conformation allows these oligomers to bind and inhibit the proteasome with low nanomolar affinity, impairing ubiquitin-dependent and ubiquitin-independent proteasome function in brain lysates. Detailed mechanistic analysis demonstrates that these oligomers inhibit the 20S proteasome through allosteric impairment of the substrate gate in the 20S core particle, preventing the 19S regulatory particle from injecting substrates into the degradation chamber. These results provide a novel molecular model for oligomer-driven impairment of proteasome function that is relevant to a variety of neurodegenerative diseases, irrespective of the specific misfolded protein that is involved.
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