The US health system faces mounting pressure to improve population health. Research suggests a need for greater coordination and alignment across the sectors that deliver medical, public health, and ...social services. This study uses sixteen years of data from a large cohort of US communities to measure the extent and nature of multisector contributions to population health activities and how these contributions affect community mortality rates. The results show that deaths due to cardiovascular disease, diabetes, and influenza decline significantly over time among communities that expand multisector networks supporting population health activities. The findings imply that incentives and infrastructure supporting multisector population health activities may help close geographic and socioeconomic disparities in population health.
The potential benefits of adding raw, non-food, lignocellulosic plant material as a carbon source for mixotrophic growth of microalgae have previously been demonstrated. This approach has advantages ...over using traditional carbon sources like glucose or acetate due to wide-spread plant biomass availability and substrate recalcitrance to bacterial contamination. Here, we report the overall growth characteristics and explore the metabolic patterns of
cultured in the presence raw plant substrate. An initial screen of plant substrate candidates showed an increase in specific growth rate and biomass accumulation when
was cultured in the presence of switchgrass or yard waste compared to media alone. We observed a near doubling of microalgal dry weight when
was grown with 0.2% (
) switchgrass under ambient CO
. Scanning electron microscopy (SEM) of corn stem after
cultivation exhibited substantial phloem degradation. Transcriptomic analyses of
during mid- and late-log phase growth revealed a dynamic metabolic landscape within many KEGG pathways. Notably, differential expression was observed for several potential glycosyl hydrolases. We also investigated the influence of switchgrass on the growth of
at 50 L volume in mini raceway ponds to determine the scalability of this approach.
We propose a 3-D-printed breast phantom for use in preclinical experimental microwave imaging studies. The phantom is derived from an MRI of a human subject; thus, it is anthropomorphic, and its ...interior is very similar to an actual distribution of fibroglandular tissues. Adipose tissue in the breast is represented by the solid plastic (printed) regions of the phantom, while fibro glandular tissue is represented by liquid-filled voids in the plastic. The liquid is chosen to provide a biologically relevant dielectric contrast with the printed plastic. Such a phantom enables validation of microwave imaging techniques. We describe the procedure for generating the 3-D-printed breast phantom and present the measured dielectric properties of the 3-D-printed plastic over the frequency range 0.5-3.5 GHz. We also provide an example of a suitable liquid for filling the fibroglandular voids in the plastic.
A series of isostructural metal−organic framework polymers of composition Cu2(L)(H2O)2 (L= tetracarboxylate ligands), denoted NOTT-nnn, has been synthesized and characterized. Single crystal X-ray ...structures confirm the complexes to contain binuclear Cu(II) paddlewheel nodes each bridged by four carboxylate centers to give a NbO-type network of 64·82 topology. These complexes are activated by solvent exchange with acetone coupled to heating cycles under vacuum to afford the desolvated porous materials NOTT-100 to NOTT-109. These incorporate a vacant coordination site at each Cu(II) center and have large pore volumes that contribute to the observed high H2 adsorption. Indeed, NOTT-103 at 77 K and 60 bar shows a very high total H2 adsorption of 77.8 mg g−1 equivalent to 7.78 wt% wt% = (weight of adsorbed H2)/(weight of host material) or 7.22 wt% wt% = 100(weight of adsorbed H2)/(weight of host material + weight of adsorbed H2). Neutron powder diffraction studies on NOTT-101 reveal three adsorption sites for this material: at the exposed Cu(II) coordination site, at the pocket formed by three {Cu2} paddle wheels, and at the cusp of three phenyl rings. Systematic virial analysis of the H2 isotherms suggests that the H2 binding energies at these sites are very similar and the differences are smaller than 1.0 kJ mol−1, although the adsorption enthalpies for H2 at the exposed Cu(II) site are significantly affected by pore metrics. Introducing methyl groups or using kinked ligands to create smaller pores can enhance the isosteric heat of adsorption and improve H2 adsorption. However, although increasing the overlap of potential energy fields of pore walls increases the heat of H2 adsorption at low pressure, it may be detrimental to the overall adsorption capacity by reducing the pore volume.
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IJS, KILJ, NUK, PNG, UL, UM
HuMax-IL8 (now known as BMS-986253) is a novel, fully human monoclonal antibody that inhibits interleukin-8 (IL-8), a chemokine that promotes tumor progression, immune escape, epithelial-mesenchymal ...transition, and recruitment of myeloid-derived suppressor cells. Studies have demonstrated that high serum IL-8 levels correlate with poor prognosis in many malignant tumors. Preclinical studies have shown that IL-8 blockade may reduce mesenchymal features in tumor cells, making them less resistant to treatment.
Fifteen patients with metastatic or unresectable locally advanced solid tumors were enrolled in this 3 + 3 dose-escalation trial at four dose levels (4, 8, 16, or 32 mg/kg). HuMax-IL8 was given IV every 2 weeks, and patients were followed for safety and immune monitoring at defined intervals up to 52 weeks.
All enrolled patients (five chordoma, four colorectal, two prostate, and one each of ovarian, papillary thyroid, chondrosarcoma, and esophageal) received at least one dose of HuMax-IL8. Eight patients had received three or more prior lines of therapy and five patients had received prior immunotherapy. Treatment-related adverse events occurred in five patients (33%), mostly grade 1. Two patients receiving the 32 mg/kg dose had grade 2 fatigue, hypophosphatemia, and hypersomnia. No dose-limiting toxicities were observed, and maximum tolerated dose was not reached. Although no objective tumor responses were observed, 11 patients (73%) had stable disease with median treatment duration of 24 weeks (range, 4-54 weeks). Serum IL-8 was significantly reduced on day 3 of HuMax-IL8 treatment compared to baseline (p = 0.0004), with reductions in IL-8 seen at all dose levels.
HuMax-IL8 is safe and well-tolerated. Ongoing studies are evaluating the combination of IL-8 blockade and other immunotherapies.
NCTN, NCT02536469. Registered 23 August 2015, https://clinicaltrials.gov/ct2/show/NCT02536469?term=NCT02536469&rank=1 .
Abstract
We found low prevalence of SARS-CoV-2 (2.7% 5/188) among pregnant and postpartum patients with universal testing. Prevalence among symptomatic patients was similar under initial targeted ...screening (22.2% 4/18) and universal approaches (19.1% 8/42). Among 170 asymptomatic patients, 2 were positive or inconclusive, respectively; repeat testing at 24 hours was negative.
We found a low prevalence of severe acute respiratory syndrome coronavirus 2 among pregnant and postpartum patients after initiation of universal testing at University of Washington–affiliated hospitals using a combination of on-site rapid testing, high-throughput centralized testing, and outpatient drive-through screening prior to admission.
Port Phillip Bay (PPB) is a large (1,930 km²), temperate embayment in southern Victoria, Australia. Extensive bay-wide surveys of PPB have occurred since 1840. In 1995/1996 the Commonwealth ...Scientific and Industrial Research Organization (CSIRO) Centre for Research on Introduced Marine Pests (CRIMP) undertook an intensive evaluation of the region with the aims of developing a comprehensive species list of native and introduced biota and contrasting previous bay-wide assessments with a current field survey in order to detect new incursions and discern alterations to native communities. Two methods were used to meet these aims: a re-evaluation of regional museum collections and published research in PPB to identify and determine the timing of introductions; and field surveys for benthic (infauna, epifauna and encrusting) organisms between September 1995 to March 1996. One hundred and sixty introduced (99) and cryptogenic (61) species were identified representing over 13% of the recorded species of PPB. As expected, the majority of these are concentrated around the shipping ports of Geelong and Melbourne. Invasions within PPB appear to be increasing, possibly due to an increase in modern shipping traffic and an increase in aquaculture (historically associated with incidental introductions); however the records of extensive biological surveys suggest that this may, in part, be an artefact of sampling effort. In contrast to Northern Hemisphere studies, PPB (and Southern Hemisphere introductions in general) have significantly different suites of successfully invading taxa. PPB is presented as one of the most invaded marine ecosystems in the Southern Hemisphere.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The detection of physiologically relevant protein isoforms encoded by the human genome is critical to biomedicine. Mass spectrometry (MS)-based proteomics is the preeminent method for protein ...detection, but isoform-resolved proteomic analysis relies on accurate reference databases that match the sample; neither a subset nor a superset database is ideal. Long-read RNA sequencing (e.g., PacBio or Oxford Nanopore) provides full-length transcripts which can be used to predict full-length protein isoforms.
We describe here a long-read proteogenomics approach for integrating sample-matched long-read RNA-seq and MS-based proteomics data to enhance isoform characterization. We introduce a classification scheme for protein isoforms, discover novel protein isoforms, and present the first protein inference algorithm for the direct incorporation of long-read transcriptome data to enable detection of protein isoforms previously intractable to MS-based detection. We have released an open-source Nextflow pipeline that integrates long-read sequencing in a proteomic workflow for isoform-resolved analysis.
Our work suggests that the incorporation of long-read sequencing and proteomic data can facilitate improved characterization of human protein isoform diversity. Our first-generation pipeline provides a strong foundation for future development of long-read proteogenomics and its adoption for both basic and translational research.
A latitudinal cline in flowering time in accessions of Arabidopsis thaliana has been widely predicted because the environmental cues that promote flowering vary systematically with latitude, but ...evidence for such clines has been lacking. Here, we report evidence of a significant latitudinal cline in flowering time among 70 Northern European and Mediterranean ecotypes when grown under ecologically realistic conditions in a common garden environment. The detected cline, however, is found only in ecotypes with alleles of the flowering time gene FRIGIDA (FRI) that lack major deletions that would disrupt protein function, whereas there is no relationship between flowering time and latitude of origin among accessions with FRI alleles containing such deletions. Analysis of climatological data suggests that late flowering in accessions with putatively functional FRI was associated with reduced January precipitation at the site of origin, consistent with previous reports of a positive genetic correlation between water use efficiency and flowering time in Arabidopsis, and the pleiotropic effects of FRI of increasing water use efficiency. In accessions collected from Southern latitudes, we detected that putatively functional FRI alleles were associated with accelerated flowering relative to accessions with nonfunctional FRI under the winter conditions of our experiment. These results suggest that the ecological function of the vernalization requirement conferred by FRI differs across latitudes. More generally, our results indicate that by combining ecological and molecular genetic data, it is possible to understand the forces acting on life history transitions at the level of specific loci.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We analyze one of the first solar energetic particle (SEP) events of solar cycle 24 observed at widely separated spacecraft in order to assess the reliability of models currently used to determine ...the connectivity between the sources of SEPs at the Sun and spacecraft in the inner heliosphere. This SEP event was observed on 2010 August 14 by near-Earth spacecraft, STEREO-A (∼80° west of Earth) and STEREO-B (∼72° east of Earth). In contrast to near-Earth spacecraft, the footpoints of the nominal magnetic field lines connecting STEREO-A and STEREO-B with the Sun were separated from the region where the parent fast halo coronal mass ejection (CME) originated by ∼88° and ∼47° in longitude, respectively. We discuss the properties of the phenomena associated with this solar eruption. Extreme ultraviolet and white-light images are used to specify the extent of the associated CME-driven coronal shock. We then assess whether the SEPs observed at the three heliospheric locations were accelerated by this shock or whether transport mechanisms in the corona and/or interplanetary space provide an alternative explanation for the arrival of particles at the poorly connected spacecraft. A possible scenario consistent with the observations indicates that the observation of SEPs at STEREO-B and near Earth resulted from particle injection by the CME shock onto the field lines connecting to these spacecraft, whereas SEPs reached STEREO-A mostly via cross-field diffusive transport processes. The successes, limitations, and uncertainties of the methods used to resolve the connection between the acceleration sites of SEPs and the spacecraft are evaluated.
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