This research identified and characterized factors that influenced nanomaterial bioavailability to three aquatic plants: Azolla caroliniana Willd, Egeria densa Planch., and Myriophyllum simulans ...Orch. Plants were exposed to 4-, 18-, and 30-nm gold nanoparticles. Uptake was influenced by nanoparticle size, the presence of roots on the plant, and dissolved organic carbon in the media. Statistical analysis of the data also revealed that particle uptake was influenced by a 4-way (plant species, plant roots, particle size, and dissolved organic carbon) interaction suggesting nanoparticle bioavailability was a complex result of multiple parameters. Size and species dependent absorption was observed that was dependent on the presence of roots and nanoparticle size. The presence of dissolved organic carbon was found to associate with 4- and 18-nm gold nanoparticles in suspension and form a nanoparticle/organic matter complex that resulted in (1) minimized particle aggregation and (2) a decrease of nanoparticle absorption by the aquatic plants. The same effect was not observed with the 30-nm nanoparticle treatment. These results indicate that multiple factors, both biotic and abiotic, must be taken into account when predicting bioavailability of nanomaterials to aquatic plants.
Introduction
Urinary tract infections (UTIs) are common infections for which initial antibiotic treatment decisions are empirically based, often without antibiotic susceptibility testing to evaluate ...resistance, increasing the risk of inappropriate therapy. We hypothesized that models based on electronic health records (EHR) could assist in the identification of patients at higher risk for antibiotic-resistant UTIs and help guide the selection of antimicrobials in hospital and clinic settings.
Methods
EHR from multiple centers in North-Central Florida, including patient demographics, previous diagnoses, prescriptions, and antibiotic susceptibility tests, were obtained for 9990 patients diagnosed with a UTI during 2011–2019. Decision trees, boosted logistic regression (BLR), and random forest models were developed to predict resistance to common antibiotics used for UTI management sulfamethoxazole-trimethoprim (SXT), nitrofurantoin (NIT), ciprofloxacin (CIP) and multidrug resistance (MDR).
Results
There were 6307 (63.1%) individuals with a UTI caused by a resistant microorganism. Overall, the population was majority female, white, non-Hispanic, and older aged (mean = 60.7 years). The BLR models yielded the highest discriminative ability, as measured by the out-of-bag area under the receiver-operating curve (AUROC), for the resistance outcomes AUROC = 0.58 (SXT), 0.62 (NIT), 0.64 (CIP), and 0.66 (MDR). Variables in the best performing model were sex, history of UTIs, catheterization, renal disease, dementia, hemiplegia/paraplegia, and hypertension.
Conclusions
The discriminative ability of the prediction models was moderate. Nonetheless, these models based solely on EHR demonstrate utility for the identification of patients at higher risk for resistant infections. These models, in turn, may help guide clinical decision-making on the ordering of urine cultures and decisions regarding empiric therapy for these patients.
BACKGROUND:Patients requiring extracorporeal membrane oxygenation (ECMO) support are critically ill and have substantial transfusion requirements, which convey both risks and benefits. A ...retrospective analysis was conducted to assess the association between blood component administration and adverse outcomes in adult, pediatric, and neonatal ECMO patients.
METHODS:We evaluated 217 ECMO patients at a single center hospitalized between January 2009 and June 2016. Three cohorts (88 adult, 57 pediatric, and 72 neonatal patients) were included for assessment of patient characteristics, blood utilization, and clinical outcomes. Univariable and multivariable analyses were used to assess the association between transfusions and clinical outcomes (primary outcomemortality and secondary outcomesmorbid events). The analysis included the main exposure of interest (total number of blood component units transfused) and potential confounding variables (age group cohort, case mix index, sex, ECMO mode and duration, and primary ECMO indication).
RESULTS:After adjustment for confounders, with each additional blood component unit transfused, there was an estimated increase in odds for mortality by 1% (odds ratio OR = 1.01; 95% confidence interval CI, 1.00–1.02; P = .013) and an increase in odds for thrombotic events by 1% (OR = 1.01; 95% CI, 1.00–1.02; P = .007). Mortality was higher in the adult (57 of 88; 64.8%) and pediatric (37 of 57; 64.9%) than in the neonatal cohort (19 of 72; 26.4%) (P < .0001). Median total blood components transfused per day followed a similar pattern for the adult (2.3 units; interquartile range IQR = 0.8–7.0), pediatric (2.9 units; IQR = 1.1–10), and neonatal (1.0 units; IQR = 0.7–1.6) cohorts (P < .0001). Over the entire hospitalization, the total median blood components transfused was highest in the neonatal (41 units; IQR = 24–94) and pediatric (41 units; IQR = 17–113) compared to the adult (30 units; IQR = 9–58) cohort (P = .007). There was no significant interaction between total units transfused over the hospital stay and age cohort for mortality (P = .35).
CONCLUSIONS:Given the association between transfusion and adverse outcomes, effective blood management strategies may be beneficial in ECMO patients.
We present the first broadband Delta *l = 1 mm spectrum toward the z = 2.56 Cloverleaf quasar, obtained with Z-Spec, a grating spectrograph on the 10.4 m Caltech Submillimeter Observatory. The ...190-305 GHz observation band corresponds to the rest frame 272-444 Delta *mm, and we measure the dust continuum as well as all four transitions of carbon monoxide (CO) lying in this range. The power-law dust emission, F Delta *n = 14 mJy( Delta *n/240 GHz)3.9 is consistent with the published continuum measurements. The CO J = 6 -> 5, J = 8 -> 7, and J = 9 -> 8 measurements are the first, and now provide the highest-J CO information in this source. Our measured CO intensities are very close to the previously published interferometric measurements of J = 7 -> 6, and we use all available transitions and our 13CO upper limits to constrain the physical conditions in the Cloverleaf molecular gas disk. We find a large mass (2-50 X 109 M ) of highly excited gas with thermal pressure nT > 106 K cm-3. The ratio of the total CO cooling to the far-IR dust emission exceeds that in the local dusty galaxies, and we investigate the potential heating sources for this bulk of warm molecular gas. We conclude that both UV photons and X-rays likely contribute, and discuss implications for a top-heavy stellar initial mass function arising in the X-ray-irradiated starburst. Finally, we present tentative identifications of other species in the spectrum, including a possible detection of the H2O \20,2 -> 11,1 transition at Delta *lrest = 303 Delta *mm.
► Thermal emission from 240 volcanic features on Io equals 55% of Io’s total heat flow. ► Energy emanating from paterae alone represents 46% of Io’s total heat flow of ∼1014W. ► Paterae heat flow has ...a bimodal longitudinal distribution (peaks at 315W and 105W). ► Slight bias towards volcanic heat flow at mid-latitudes; also, a minimum at ∼200W. ► Peak thermal emission offset eastwards from asthenospheric tidal heating models.
We have examined thermal emission from 240 active or recently-active volcanic features on Io and quantified the magnitude and distribution of their volcanic heat flow during the Galileo epoch. We use spacecraft data and a geological map of Io to derive an estimate of the maximum possible contribution from small dark areas not detected as thermally active but which nevertheless appear to be sites of recent volcanic activity. We utilize a trend analysis to extrapolate from the smallest detectable volcanic heat sources to these smallest mapped dark areas. Including the additional heat from estimates for “outburst” eruptions and for a multitude of very small (“myriad”) hot spots, we account for ∼62×1012W (∼59±7% of Io’s total thermal emission). Loki Patera contributes, on average, 9.6×1012W (∼9.1±1%). All dark paterae contribute 45.3×1012W (∼43±5%). Although dark flow fields cover a much larger area than dark paterae, they contribute only 5.6×1012W (∼5.3±0.6%). Bright paterae contribute ∼2.6×1012W (∼2.5±0.3%). Outburst eruption phases and very small hot spots contribute no more than ∼4% of Io’s total thermal emission: this is probably a maximum value. About 50% of Io’s volcanic heat flow emanates from only 1.2% of Io’s surface. Of Io’s heat flow, 41±7.0% remains unaccounted for in terms of identified sources. Globally, volcanic heat flow is not uniformly distributed. Power output per unit surface area is slightly biased towards mid-latitudes, although there is a stronger bias toward the northern hemisphere when Loki Patera is included. There is a slight favoring of the northern hemisphere for outbursts where locations were well constrained. Globally, we find peaks in thermal emission at ∼315°W and ∼105°W (using 30° bins). There is a minimum in thermal emission at around 200°W (almost at the anti-jovian longitude) which is a significant regional difference. These peaks and troughs suggest a shift to the east from predicted global heat flow patterns resulting from tidal heating in an asthenosphere. Global volcanic heat flow is dominated by thermal emission from paterae, especially from Loki Patera (312°W, 12°N). Thermal emission from dark flows maximises between 165°W and 225°W. Finally, it is possible that a multitude of very small hot spots, smaller than the present angular resolution detection limits, and/or cooler, secondary volcanic processes involving sulphurous compounds, may be responsible for at least part of the heat flow that is not associated with known sources. Such activity should be sought out during the next mission to Io.
The molecular pathways driving mesenchymal glioblastoma (GBM) are still not well understood. We report here that truncated glioma-associated oncogene homolog 1 (tGLI1) is a tumor-specific ...transcription factor that facilitates GBM growth, is enriched in the mesenchymal subtype of GBM and glioma stem cells (GSC), and promotes mesenchymal GSC by upregulating transcription of CD44. In an orthotopic GBM xenograft mouse model, tGLI1-overexpressing tumors grew more aggressively with increased proliferation and angiogenesis compared with control and GLI1-overexpressing xenografts. tGLI1 was highly expressed in GBM clinical specimens but undetectable in normal brains, whereas GLI1 was expressed in both tissues. A t
LI1 activation signature (tGAS) correlated with glioma grade, tumor angiogenesis, and poor overall survival, and GBMs with high tGAS were enriched with mesenchymal GBM/GSC gene signatures. Neurospheres contained increased levels of tGLI1, but not GLI1, compared with the monolayer culture; mesenchymal GSC expressed more tGLI1 than proneural GSC. Ectopic tGLI1 expression enhanced the ability of mesenchymal GSC to yield neurospheres
and to form tumors in mouse brains. Selective tGLI1 knockdown reduced neurosphere formation of GBM cells. tGLI1 bound to and transactivated the promoter of the CD44 gene, a marker and mediator for mesenchymal GSC, leading to its expression. Collectively, these findings advance our understanding of GBM biology by establishing tGLI1 as a novel transcriptional activator of CD44 and a novel mediator of mesenchymal GBM and GSC.
These findings highlight the role of a tumor-specific gain-of-function transcription factor tGLI1 in mesenchymal glioma stem cell maintenance and mesenchymal GBM growth.
.
Display omitted
•AA7075/TiB2 composites with up to 24 vol% TiB2 are produced with friction consolidation. TiB2 fragmented into submicron- and micron-sized particles by intense deformation.•24 vol% ...composite has a very high strength of 672 MPa and a wear rate of 5.7x10−5 mm3/Nm, both of which surpasses the other AMC examples in the literature.•Microstructure-based FE simulations predict the theoretical strength of ∼730 MPa and the failure mechanisms in the composites. Strain localization in between the particles limits the ductility.
The friction consolidation method successfully reinforced aluminum 7075 alloy (AA7075) with high-volume fractions (12 and 24 vol%) of titanium diboride (TiB2) by high pressure and severe plastic deformation at elevated temperatures. The consolidated AMCs have a uniform dispersion of submicron- and micron-sized TiB2 particles in the AA7075 matrix, with significant refinement of the matrix grain size and the particles. The addition of TiB2 significantly increases hardness by up to 50 %, Young’s modulus by up to 62 %, and ultimate tensile strength by up to 28 % to 672 MPa, while reducing ductility by 80 %. Wear resistance of 7075/24 vol% TiB2 improves seven-fold compared to baseline, making it comparable to that of carburized steels. Microstructure-based finite element modeling provided a theoretical strength limit of ∼730 MPa for the composites and indicated that high triaxiality in conjunction with severe equivalent plastic strain in a narrow area between the TiB2 particles led to early fracture initiations, limiting the ductility.
Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of ...post-treatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance.
This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at 8 U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154).
The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pre-treatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had 3 or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% (95%CI: 87.5-97.5) and 87.3% (95%CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95%CI: 98.9-99.8) and 98.4% (95%CI: 97.3-99.5), respectively.
TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue re-imaging following first disease restaging and could inform future surveillance practice. Additional study of how pre-treatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.
Purpose: Identification of novel biomarkers and immunotherapy targets for prostate cancer (PCa) is crucial to better diagnosis and
therapy. We sought to identify novel PCa tumor-associated antigens ...(TAA) that are expressed in PCa, absent in nonprostate
human tissue, and immunogenic for immune responses restricted by human HLA.
Experimental Design and Results: Using microarray analysis of normal and cancerous human prostate tissues, we identified 1,063 genes overexpressed in PCa.
After validating 195 transcripts in publicly available array data sets, we interrogated expression of these TAAs in normal
human tissues to identify genes that are not expressed at detectable levels in normal, nonprostate adult human tissue. We
identified 23 PCa TAA candidates. Real-time PCR confirmed that 15 of these genes were overexpressed in PCa ( P < 0.05 for each). The most frequently overexpressed gene, single-minded homologue 2 ( SIM2 ), was selected for further evaluation as a potential target for immunotherapy. ELISA assay revealed that a fraction of PCa
patients exhibited immune responsiveness to SIM2 as evidenced by the presence of autoantibodies to SIM2 in their sera. We
next showed binding of putative HLA-A2.1–restricted SIM2 epitopes to human A2.1, and immunization of transgenic HLA-A2.1 mice
showed induction of SIM2-specific CTL responses in vivo .
Conclusions: Our findings that SIM2 is selectively expressed in PCa, that human HLA-A2.1–restricted SIM2 epitopes induce specific T cells
in vivo , and that anti-SIM2 antibodies are detectable in PCa patients' sera implicate SIM2 as a PCa-associated antigen that is a
suitable potential target for PCa immunotherapy. (Clin Cancer Res 2009;15(18):5794–802)
The COVID-19 pandemic necessitates aggressive infection mitigation strategies to reduce the risk to patients and healthcare providers. This document is intended to provide a framework for the adult ...cardiac surgeon to consider in this rapidly changing environment. Preoperative, intraoperative, and postoperative detailed protective measures are outlined. These are guidance recommendations during a pandemic surge to be used for all patients while local COVID-19 disease burden remains elevated.
Display omitted
PDF
