Evidence-based insertion and maintenance bundles are effective in reducing the incidence of central line-associated bloodstream infections (CLABSI) in intensive care unit (ICU) settings. We studied the adoption and compliance of CLABSI prevention bundle programs and CLABSI rates in ICUs in a large network of acute care hospitals across Canada.

The environmental conditions for the origin of life are still not well-constrained, but membrane-bound structures must have been key to the origin of life. Membranes composed of fatty acids are promising candidates due to their simplicity and plausible prevalence in prebiotic environments. To assess the stability of membranes composed of fatty acids with tail lengths ranging from 12 to 16 carbons at different temperatures and sodium chloride concentrations that may have existed on the early Earth, we conducted all-atom molecular dynamics (MD) simulations. In the absence of salt (freshwater), none of the fatty acids exhibited bilayer formation, whether below or above their chain melting temperature. However, elevating the salt concentration from 0.15 M (saline solution), 0.5 M (seawater), 1 M (seawater tide pools), 3 M (salty tide pools) and 5 M (Dead Sea) resulted in the formation of stable bilayers. The 16-carbon fatty acid required lower salt concentration, while shorter, 12-carbon chain necessitated higher salt levels. Increasing the salt concentration led to three main effects: (1) increased bilayer thickness, (2) reduced area per fatty acid and (3) elevated deuterium order parameter of the chains, resulting in more robust membranes. Our simulations indicated that the salt cations aggregated on the bilayer surfaces, effectively mitigating repulsive interactions among hydrophilic fatty acid head groups. These findings suggest that fatty acid bilayers are more likely present in ancient waters connected to saltwater reservoirs, or seawater tide pools with elevated salt concentrations.

While clinical research intends to improve health outcomes for all, access to research participation is often limited and inequitable. Geographic proximity is a recognized barrier, thus, systemic infrastructure solutions through federal programs including General Clinical Research Centers and Clinical and Translational Science Awards have sought to improve accessibility. Even with such support, academic medical centers often have limited clinical research-dedicated space apart from shared exam rooms in difficult-to-navigate hospitals or clinics. In 2019, the Duke University School of Medicine looked beyond its medical center campus to identify free-standing sites within Durham communities for participant study visits. Catalyzed by the COVID-19 pandemic, Duke Research at Pickett, a 22 000-square-foot building with a laboratory, 30 exam rooms, and on-site parking, opened in October 2020 to support vaccine and treatment trials. Upon the lifting of many COVID-19 restrictions, and in partnership with the Research Equity and Diversity Initiative (READI) Community Advisory Council, the building was transformed to encourage community gatherings, education, and training programs. To date, Duke Research at Pickett has hosted 2692 participants in 78 research trials and 14 community-engaged activities.

Palmer amaranth (Amaranthus palmeri S. Watson, AMAPA) is one of the most troublesome weeds in North America due to its rapid growth rate, substantial seed production, competitiveness and the evolution of herbicide-resistant populations. Though frequently encountered in the South, Midwest, and Mid-Atlantic regions of the United States, A. palmeri was recently identified in soybean [Glycine max (L.) Merr.] fields in Genesee, Orange, and Steuben counties, NY, where glyphosate was the primary herbicide for in-crop weed control. This research, conducted in 2023, aimed to (1) describe the dose response of three putative resistant NY A. palmeri populations to glyphosate, (2) determine their mechanisms of resistance, and (3) assess their sensitivity to other postemergence herbicides commonly used in NY crop production systems. Based on the effective dose necessary to reduce aboveground biomass by 50% (ED50), the NY populations were 42 to 67 times more resistant to glyphosate compared with a glyphosate-susceptible population. Additionally, the NY populations had elevated EPSPS gene copy numbers ranging from 25 to 135 located within extrachromosomal circular DNA (eccDNA). Label rate applications of Weed Science Society of America (WSSA) Group 2 herbicides killed up to 42% of the NY populations of A. palmeri. Some variability was observed among populations in response to WSSA Group 5 and 27 herbicides. All populations were effectively controlled by labeled rates of herbicides belonging to WSSA Groups 4, 10, 14, and 22. Additional research is warranted to confirm whether NY populations have evolved multiple resistance to herbicides within other WSSA groups and to develop effective A. palmeri management strategies suitable for NY crop production.

The natural tidelands sediments along the north shore of San Pablo Bay, California, are neutral in reaction and subjected to a wet, reducing environment conducive to ferrous sulfide accumulation. When the sediments are diked and drained, the environment rapidly becomes oxidizing and generally dry. Oxidation of the ferrous sulfide results in extremely acid cat clays within a year or two.

Undrained sediments from the area contain montmorillonite, chlorite, mica, and kaolinite that all give sharp X-ray diffraction patterns. Sediments drained for 6 years, although strongly acid, have virtually the same clay mineralogy as the undrained sediments. However, sediments drained for 60 years show a general deterioration of crystalline clay minerals, particularly chlorite. The deterioration decreases with depth until the deeper zones closely resemble the undrained sediments.

In separate laboratory experiments, chlorites were formed in an oxidized soil that was subjected to reducing conditions simulating the environment of the undrained tidelands sediments. The possibility exists, therefore, that chlorites in the undrained sediments may have formed subsequent to deposition.

As regional chronologies become better defined, we are better able to track large-scale population movements and related cultural change. A dataset of 156 radiocarbon dates from the Middle Cumberland Region (MCR), evaluated with 199 more dates from the Ridge and Valley portions of northern Georgia and East Tennessee, enable modeling of population movements from the Central Mississippi Valley into the MCR, as well as subsequent movements and effects in the Ridge and Valley between AD 1200 and 1450. The dissolution of Cahokia is of particular interest, because the MCR falls geographically between the American Bottom and the Ridge and Valley province. This large-scale chronological perspective places key events in this part of the Southeast and Midwest into a unified historical framework that increases our understanding of the timing of cultural events. A related goal is to sort out possible external events and influences that may have affected this large region. This study makes apparent the relationships between cultural events and natural events, such as the drought sequences reported for the Central Mississippi Valley and beyond.

Formation of authigenic trioctahedral Mg-rich smectite is common in evaporative lake sediments, but was not described previously in modern marine evaporative environments. This study documents formation of authigenic K-rich, Mg-smectite during very early diagenesis in the dominantly siliciclastic Salina Ometepec (Baja California), a large supratidal evaporative sabkha complex near the mouth of the Colorado River. Here, sediment pore waters are exceptionally Mg2+-rich relative to other marine evaporative environments due to suppressed sulfate reduction which limits production of carbonate alkalinity and, hence, carbonate (particularly dolomite) precipitation. Sediment cores were obtained along a five km transect seaward across the hypersaline mud flat to evaluate how these atypical geochemical conditions would affect the clay mineral compositions.

Scanning transmission electron microscopy (STEM) observations show that the smectite from the marine Inlet, near the sediment source, consists of grains of irregular shape that give selected area diffraction (SAED) patterns reflecting dominant turbostratic stacking. Analytical electron microscopy (AEM) analyses indicate that K+ is the dominant interlayer cation; the mean composition is approximately K0.7(Al3.3Fe(III)0.3Mg0.5)(Al0.5Si7.5)O20(OH)4. Such smectite is implied to be detrital in part because it is similar to smectite known to be deposited by the Colorado River.

Smectite from the hypersaline mud flat occurs as aggregates of small subhedral pseudohexagonal plate or lath-shaped crystals ≤250 nm in diameter, with thicknesses varying between three and ten layers. The SAED patterns reflect substantial turbostratic stacking, but with a greater frequency of interlayer coherency as compared with detrital smectite. Crystals from greater sediment depths are larger and more nearly euhedral. This smectite is dominantly trioctahedral, with mean composition approximately K0.7(Al0.7Fe(III)0.5Mg4.45)(Al1.2Si6.8)O20(OH)4 (saponitic). This smectite is inferred to be dominantly authigenic in origin.

The X-ray diffraction (XRD) and STEM/AEM data collectively imply that detrital aluminous dioctahedral smectite reacts to form authigenic Mg-rich trioctahedral smectite, driven in part by the high Mg2+/ Ca2+ ratio of pore waters. Such early-formed Mg-rich smectite may be the precursor for the trioctahedral mixed-layer smectite, corrensite, and chlorite assemblages found in ancient marine evaporative sequences. These results also add to the accumulating evidence that interlayer K+ in marine smectite is fixed during the earliest stages of marine diagenesis near the sediment water interface.

We calculated the attributable cost of several healthcare-associated infections in a community hospital network: central-line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), hospital-onset Clostridioides difficile infections (CDI-HOs) (43 hospitals); surgical site infections (SSIs) (40 hospitals). From 2016 to 2022, the total cost of CLABSIs, CAUTIs, CDI-HOs, and SSIs was $420,012,025.

Consumption of probiotics and/or yogurt could be a solution for restoring the balance of the gut microbiota. This study examined associations of regular intake of probiotic supplements or yogurt with the gut microbiota among a diverse population of older adults (N=1,861; 60–72 years). Faecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 region). General linear models were used to estimate the associations of probiotic supplement or yogurt intake with microbiome measures adjusting for covariates. Compared to non-yogurt consumers (N=1,023), regular yogurt consumers (≥once/week, N=818) had greater Streptococcus (β=0.29, P=0.0003) and lower Odoribacter (β=−0.33, P<0.0001) abundance. The directions of the above associations were consistent across the five ethnic groups but stronger among Japanese Americans (Streptococcus: β=0.56, P=0.0009; Odoribacter: β=−0.62, P=0.0005). Regular intake of probiotic supplements (N=175) was not associated with microbial characteristics (i.e., alpha diversity and the abundance of 152 bacteria genera). Streptococcus is one of the predominant bacteria genera in yogurt products, which may explain the positive association between yogurt consumption and Streptococcus abundance. Our analyses suggest that changes in Odoribacter were independent of changes in Streptococcus abundance. Future studies may investigate whether these microbial genera and their sub-level species mediate potential pathways between yogurt consumption and health.

OBJECTIVES/GOALS: Aiming to better understand the molecular pathogenesis of familial partial lipodystrophy (PL), we initiated whole-exome sequencing for our patients with PL syndromes. A novel variant of early B cell factor 2 (EBF2) was identified. Here we report the biological impact of a novel truncating EBF2 variant. METHODS/STUDY POPULATION: Using 3T3-L1 and human primary subcutaneous preadipocytes, we performed loss-of-function and gene rescue experiments. All cells were cultured in DMEM with 10% bovine calf serum (Invitrogen) at 5% CO2. After lentivirus transfection, cells were grown to confluence and then exposed to adipogenesis induction media containing dexamethasone (0.25µM), insulin (1µg/ml) and isobutyl methylxanthine (0.5 mM). Total RNA was extracted using RNeasy Mini Kit (Qiagen) and cDNA was synthesized using IScript (Bio-Rad). Real-time qPCR was performed using TaqMan probes for Pparg and Fabp4, two key adipogenesis markers. RESULTS/ANTICIPATED RESULTS: Patient was found to carry a heterozygous nonsense mutation in exon 6 of EBF2, causing the premature termination of the protein at amino acid position 165. Adipogenesis was significantly suppressed in 3T3L1 cells when endogenous Ebf2 was suppressed with siRNA and lentiviral shRNA. Adipocytes with suppressed Ebf2 expression showed marked reduction of intracellular lipid content and Pparg and Fabp4 expression (>80% reduction). With lentiviral gene transfer, EBF2 fully rescued adipogenic potential, whereas the truncated variant EBF2 did not. Of note, 3T3-L1 cells transfected with the EBF2 variant displayed impaired adipogenesis, suggesting a dominant-negative effect of the EBF2 variant on adipogenesis. We confirmed the dominant effect of the EBF2 variant in human adipocyte differentiation. DISCUSSION/SIGNIFICANCE: Our data suggest that EBF2 is indispensable for adipogenesis. The loss of function and dominant-negative effect of the truncating variant of EBF2 likely plays a pathogenic role in PL. Whole exome sequencing of PL patients and ex-vivo functional analysis help identify novel gene variants and better understand the molecular pathogenesis of PL.

We present the first unbiased survey of neutral hydrogen absorption in the Small Magellanic Cloud. The survey utilises pilot neutral hydrogen observations with the Australian Square Kilometre Array Pathfinder telescope as part of the Galactic Australian Square Kilometre Array Pathfinder neutral hydrogen project whose dataset has been processed with the Galactic Australian Square Kilometre Array Pathfinder-HI absorption pipeline, also described here. This dataset provides absorption spectra towards 229 continuum sources, a 275% increase in the number of continuum sources previously published in the Small Magellanic Cloud region, as well as an improvement in the quality of absorption spectra over previous surveys of the Small Magellanic Cloud. Our unbiased view, combined with the closely matched beam size between emission and absorption, reveals a lower cold gas faction (11%) than the 2019 ATCA survey of the Small Magellanic Cloud and is more representative of the Small Magellanic Cloud as a whole. We also find that the optical depth varies greatly between the Small Magellanic Cloud’s bar and wing regions. In the bar we find that the optical depth is generally low (correction factor to the optically thin column density assumption of $\mathcal{R}_{\mathrm{HI}} \sim 1.04$ ) but increases linearly with column density. In the wing however, there is a wide scatter in optical depth despite a tighter range of column densities.

We present the most sensitive and detailed view of the neutral hydrogen ( ${\rm H\small I}$ ) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ( $1.6\,\mathrm{mJy\ beam}^{-1}$ ) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ ( ${\sim}10\,\mathrm{pc}$ ). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.

As past usual diet quality may affect gut microbiome (GM) composition, we examined the association of the Healthy Eating Index (HEI)-2015 assessed 21 and 9 years before stool collection with measures of fecal microbial composition in a subset of the Multiethnic Cohort. A total of 5936 participants completed a validated quantitative FFQ (QFFQ) at cohort entry (Q1, 1993–1996), 5280 at follow-up (Q3, 2003–2008) and 1685 also at a second follow-up (Adiposity Phenotype Study (APS), 2013–2016). All participants provided a stool sample in 2013–2016. Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 regions). HEI-2015 scores were computed based on each QFFQ. Using linear regression adjusted for relevant covariates, we calculated associations of HEI-2015 scores with gut microbial diversity and 152 individual genera. The mean HEI-2015 scores increased from Q1 (67 (sd 10)) to Q3 (71 (sd 11)) and APS (72 (sd 10)). Alpha diversity assessed by the Shannon Index was significantly higher with increasing tertiles of HEI-2015. Of the 152 bacterial genera tested, seven (Anaerostipes, Coprococcus_2, Eubacterium eligens, Lachnospira, Lachnospiraceae_ND3007, Ruminococcaceae_UCG-013 and Ruminococcus_1) were positively and five (Collinsella, Parabacteroides, Ruminiclostridium_5, Ruminococcus gnavus and Tyzzerella) were inversely associated with HEI-2015 assessed in Q1, Q3 and APS. The estimates of change per unit of the HEI-2015 score associated with the abundance of these twelve genera were consistent across the three questionnaires. The quality of past diet, assessed as far as ∼20 years before stool collection, is equally predictive of GM composition as concurrently assessed diet, indicative of the long-term consistency of this relation.