Single-molecule techniques to analyze proteins and other biomolecules involving labels and tethers have allowed for new understanding of the underlying biophysics; however, the impact of perturbation from the labels and tethers has recently been shown to be significant in several cases. New approaches are emerging to measure single proteins through light scattering without the need for labels and ideally without tethers. Here, the approaches of interference scattering, plasmonic scattering, microcavity sensing, nanoaperture optical tweezing, and variants are described and compared. The application of these approaches to sizing, oligomerization, interactions, conformational dynamics, diffusion, and vibrational mode analysis is described. With early commercial successes, these approaches are poised to have an impact in the field of single-molecule biophysics.

Background: There is limited data regarding the benefits of direct inoculation of sterile pericardial fluid into blood culture bottles. We discovered widespread adoption of this practice at our institution during pericardiocenteses and became concerned about over-capturing of skin flora contaminants. We aimed to understand how organisms detected in pericardial fluid inoculated into blood culture bottles were interpreted clinically. Methods: We investigated a cluster of four patients with coagulase-negative Staphylococcus (CoNS) isolated in pericardial fluid inoculated blood culture bottles (PF-BCxBs) over a 2-week period; three of these patients had recent cardiac surgery and were initially flagged as potential SSIs. We further expanded to a retrospective review and identified 28 patients with ≥1 organism isolated from PF-BCxBs from 7/2021 to 6/2023. Clinical, microbiological, and pharmacy data were abstracted. The primary outcome was the proportion of patients with a clinically diagnosed infection. Results: Investigation into the initial cluster revealed a pseudo-outbreak - three of four patients had no clinical evidence of infection (CoNS was deemed a contaminant); one was treated for a potential infection. All patients had concomitant negative routine fluid cultures. Discussions with the cardiology teams revealed areas for improvement in the process for inoculating fluid into blood culture bottles. From the two-year review, 18% (5/28) of patients were clinically diagnosed with an infection (two Staphylococcus aureus; two CoNS; one Candida rugosa). Of the patients without Staphylococcus aureus, all three had a concomitant negative routine fluid culture, were receiving antibiotics prior to pericardiocentesis, and had white blood cell counts (WBC) >12 K/uL. The remaining 82% (23/28) of patients were deemed not to have an infection. Of these 23 patient without infection, organisms isolated were 16 CoNS (70%) and seven Cutibacterium species (30%). None of these patients had a fever, one (4%) was receiving pre-pericardiocentesis antibiotics, and three (9%) had WBC >12 K/uL. 70% (16/23) of these patients were started on antibiotics after gram-stain results; all were eventually discontinued (mean antibiotic days = 2, range 1-5 days). 83% (19/23) of these patients had a concomitant negative routine fluid culture. Conclusion: The majority of patients with an organism isolated from PF-BCxBs had either CoNS or Cutibacterium species and were deemed not to have a clinical infection. Within the small cohort limitations, clinical utility of blood culture bottle inoculation seems highest for patients with pre-procedural concern for infection. IPC teams should be aware of the non-pathogenic skin flora frequency and potential implication on SSI surveillance.

This study uses isotope and microbotanical data from the analysis of teeth and dental calculus to investigate camelid diet and foddering practices at Quilcapampa (AD 835–900). By providing taxonomically specific evidence of foods consumed, botanical data from dental calculus complement the more general impressions of photosynthetic pathways obtained through isotopic analysis. Results suggest that the camelid diet incorporated maize (Zea mays), algarrobo (Prosopis sp.), potato chuño (Solanum sp.), and other resources. The life-history profile of one camelid (Individual 3) reveals dietary change from mainly C3 plants to more C4 plant contributions as the animal aged. This pattern is supported by carbonate isotope results indicating that this individual spent its youth in the mid-valley ecozone before becoming more mobile later in life. As this life-history example shows, isotopic and microbotanical analyses are complementary approaches, clarifying a pattern of seasonal transhumance that linked the lives of humans and animals along the Middle Horizon (AD 600–1000) caravan networks that crisscrossed the central Andes.

The letter of the law is its literal meaning. Here, the spirit of the law is its perceived intention. We tested the hypothesis that violating the spirit of the law accounts for culpability above and beyond breaking the mere letter. We find that one can incur culpability even when the letter of the law is not technically broken. We examine this effect across various legal contexts and discuss the implications for future research directions.

Stakeholder engagement is increasingly expected by funders and valued by researchers in clinical and translational science, yet many researchers lack access to expert consultation or training in selecting appropriate stakeholder engagement methods. We describe the development of a novel Stakeholder Engagement Navigator webtool. We conducted an environmental scan and literature review, along with investigator interviews, surveys, and engagement expert facilitated group discussion. We formally reviewed and cataloged 29 distinct engagement methods. To develop the webtool, we used an iterative design process that followed Design Thinking phases: empathize, define, ideate, prototype, and test. As prioritized during user testing, the Stakeholder Engagement Navigator webtool both educates and guides investigators in selecting an engagement method based on key criteria. The V1.0 Navigator webtool filters methods first by purpose of engagement (noted by 62% of users as the highest priority criteria), then by budget, time per stakeholder interaction, and total interactions. The tool is available at DICEMethods.org. The Stakeholder Engagement Navigator webtool is a user-centered, interactive webtool suitable for use by researchers seeking guidance on appropriate stakeholder engagement methods for clinical and translational research projects.

We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$ 11–18 arcsec, resulting in a catalogue of $\sim$ 220 000 sources, of which $\sim$ 180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.

Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.