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Background: Obtaining intravenous access in hypotensive patients is challenging and may critically delay resuscitation. The Graduated Vascular Access for Hypotensive Patient (GAHP) protocol leverages intraosseous fluid boluses to specifically dilate proximal veins. This study aims to evaluate the efficacy of GAHP in maximizing venous targets through early distal intraosseous access and a small fluid bolus. Methods: This was a prospective randomized cadaveric pilot study to evaluate extremity venous engorgement during intraosseous infusion. Cadavers (n = 23) had an intraosseous needle inserted into four sites: distal radius, proximal humerus, distal femur, and distal tibia. Intraosseous saline was rapidly infused, venous optimization was measured using real-time ultrasound. Primary outcome was maximum vessel circumference increase with intraosseous infusion. Secondary outcomes were: time to maximum circumference, and infusion volume required. Statistical analyses included Levene’s test for equality of variances, Wilcoxon signed-rank test, and generalized estimating equation. Results: There was a significant mean increase of 1.03 cm (95% CI 0.86, 1.20), representing a difference of 102%. We found no significant difference in time to optimize vessel circumference across sites, but volume required significantly differed. Conclusion: GAHP quickly and effectively increased the circumference of anatomically adjacent veins. Anatomical sites did not differ on time to reach maximum enlargement of vessels following intraosseous infusion but did differ in terms of volume required to maximize vessel circumference. Further research is needed using live, hypotensive patients.

Background: Inorganic polyphosphates (polyPs) are linear chains of phosphates that accelerate blood clotting. Targeting polyP in vivo has been shown to reduce thrombosis. Objectives: To identify and characterize anti-polyP monoclonal antibodies that could be used as analytical tools and as antithrombotic agents. Methods: Hybridomas were prepared from spleen cells from autoimmune NZBWF1/J female mice and screened for anti-polyP antibodies. Antibodies that bound polyP using enzyme-linked immunosorbent assay and pull-down assays were further characterized with plate binding, surface plasmon resonance, and plasma-based clotting assays. Antithrombotic potential was evaluated in a murine ferric chloride–induced carotid artery thrombosis model. Results: Of 4 antibodies that bound polyP in our pull-down assay, 2 (PP2069 and PP2099) were available for further characterization. While analyzing these anti-polyP antibodies, we found secretory leukocyte peptidase inhibitor (SLPI) to be a common contaminant of these antibodies and that SLPI binds polyP. We removed SLPI quantitatively from our purified immunoglobulin G. Both PP2069 and PP2099 immunoglobulin G displayed high affinity for polyP but also bound to other polyanions such as DNA, heparin, and certain other glycosaminoglycans, indicating limited specificity. Both antibodies inhibited polyP-initiated plasma clotting in vitro. When tested in vivo in a mouse thrombosis model, however, neither PP2069 nor PP2099 exhibited a significant antithrombotic effect. Conclusion: Autoimmune mice spontaneously produce antibodies against polyP. The 2 examples of anti-polyP monoclonal antibodies studied here not only bound to polyP with high affinity but also cross-reacted with DNA and heparin. Neither antibody protected against thrombosis in a mouse model, but they might have some utility for in vitro studies of polyP.

Growth differentiation factor-15 (GDF-15) is an emerging biomarker in several conditions. This SLR, conducted following PRISMA guidelines, examined the association between GDF-15 concentration and range of adverse outcomes in patients with heart failure (HF). Publications were identified from Embase® and Medline® bibliographic databases between January 1, 2014, and August 23, 2022 (congress abstracts: January 1, 2020, to August 23, 2022). Sixty-three publications met the eligibility criteria (55 manuscripts and 8 abstracts; 45 observational studies and 18 post hoc analyses of randomized controlled trials [RCTs]). Of the 19 outcomes identified, the most frequently reported longitudinal outcomes were mortality (n = 32 studies; all-cause [n = 27] or cardiovascular-related [n = 6]), composite outcomes (n = 28; most commonly mortality ± hospitalization/rehospitalization [n = 19]), and hospitalization/re-hospitalization (n = 11). The most common cross-sectional outcome was renal function (n = 22). Among longitudinal studies assessing independent relationships with outcomes using multivariate analyses (MVA), a significant increase in risk associated with higher baseline GDF-15 concentration was found in 22/24 (92 %) studies assessing all-cause mortality, 4/5 (80 %) assessing cardiovascular-related mortality, 13/19 (68 %) assessing composite outcomes, and 4/8 (50 %) assessing hospitalization/rehospitalization. All (7/7; 100 %) of the cross-sectional studies assessing the relationship with renal function by MVA, and 3/4 (75 %) assessing exercise capacity, found poorer outcomes associated with higher baseline GDF-15 concentrations. This SLR suggests GDF-15 is an independent predictor of mortality and other adverse but nonfatal outcomes in patients with HF. A better understanding of the prognostic role of GDF-15 in HF could improve clinical risk prediction models and potentially help optimize treatment regimens.

Summary: Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master metabolic regulator that is active in nearly all proliferating eukaryotic cells; however, it is unclear whether mTORC1 activity changes throughout the cell cycle. We find that mTORC1 activity oscillates from lowest in mitosis/G1 to highest in S/G2. The interphase oscillation is mediated through the TSC complex but is independent of major known regulatory inputs, including Akt and Mek/Erk signaling. By contrast, suppression of mTORC1 activity in mitosis does not require the TSC complex. mTORC1 has long been known to promote progression through G1. We find that mTORC1 also promotes progression through S and G2 and is important for satisfying the Chk1/Wee1-dependent G2/M checkpoint to allow entry into mitosis. We also find that low mTORC1 activity in G1 sensitizes cells to autophagy induction in response to partial mTORC1 inhibition or reduced nutrient levels. Together, these findings demonstrate that mTORC1 is differentially regulated throughout the cell cycle, with important phase-specific consequences for proliferating cells.

A 16-year-old girl with Loeys-Dietz syndrome presented with an acute, complicated type B aortic dissection (AD) with mesenteric and right renal malperfusion owing to a dynamic obstruction. The anatomy of her AD and her genetic aortography were suboptimal for thoracic endovascular aortic repair. Given the concern for anticipated late aortic degeneration and the need for open aortic repair, she underwent successful transfemoral endovascular septal fenestration with stenting of the fenestration into the superior mesenteric artery and additional stenting of the right renal artery. Her renal failure and mesenteric angina resolved, and she was discharged home. Endovascular fenestration provides an elegant solution for AD-associated dynamic malperfusion of aortic branch vessels without compromising future open aortic repairs.

Current research into the digital healthcare landscape reveals a significant gap in understanding the perspectives of consumers with lived health experiences on sharing their health data for research purposes. Despite the substantial value that such shared information can bring to healthcare research, policy development, and system improvement, insights into the attitudes and willingness of these consumers towards data sharing remain sparse. This study seeks to fill this gap, exploring the unique views of these individuals and assessing the potential benefits their data sharing could contribute to healthcare.Utilising three focus groups, this qualitative study engaged 25 consumers with chronic health conditions to explore their attitudes towards sharing their personal health data for research. Conducted in Western Australia, the sessions were adapted to online and face-to-face settings due to COVID-19 restrictions. Discussions were recorded, transcribed and analysed using a reflexive thematic approach to capture the diverse perspectives and experiences of the participants.The study revealed critical insights into how consumers with lived health experiences perceive the sharing of their health data for research. Key themes identified included data management and privacy concerns, the importance of transparent and patient-centric data governance models, and the varying levels of consumer trust in healthcare data-sharing processes.This research provides valuable contributions towards developing a more inclusive and effective framework for health data sharing in research. By understanding the unique perspectives of consumers with lived health experiences, the study provides an understanding of enhancing consumer trust and participation in data-sharing initiatives. These insights are crucial for improving the quality and relevance of healthcare delivery, research, and policy-making, ultimately benefiting the broader healthcare sector.

The European Centre for Disease Prevention and Control (ECDC) defines a case of tick-borne encephalitis (TBE) as an infection by the TBE virus (TBEV) with clinical manifestations of central nervous system inflammation (e.g., meningitis, encephalitis). To better understand the TBE surveillance landscape, online searches were conducted to determine if cases of TBE, TBEV infection, acute meningitis or encephalitis, or viral meningitis or encephalitis were subject to statutory reporting in European countries in 2023. In countries with statutory reporting, notification responsibility and available information on surveillance-reported cases were determined. The number of TBE cases reported to ECDC were compared with the number of cases recorded in national surveillance reports. Of 44 countries of the Europe Region of the United Nations, 37 (84 %) mandated statutory reporting of cases of TBE, TBEV infection, or acute/viral meningitis/encephalitis. Twenty-six (87 %) of 30 countries with identified surveillance reports recorded TBE cases in 2020–2023. Of these countries, 17 (65 %) required TBE reporting by clinicians and laboratories, 5 (19 %) by clinicians only, and 4 (15 %) by laboratories only. Twenty-four countries reported on TBE cases to ECDC in 2020; however, surveillance for TBE in Europe is heterogeneous. Standardization of TBE surveillance would enhance the understanding of TBE disease burden in Europe.

Since the 1998 Master Settlement Agreement in the U.S., many studies have examined the associations between tobacco control policies and smoking; however, there is a need to comprehensively examine the impact of these policies on sociodemographic disparities in cigarette smoking. This protocol outlines a systematic review that seeks to fill this gap. Quantitative observational, experimental, and quasi-experimental studies are eligible for inclusion. Policies include cigarette taxes, smoke-free air laws, anti-tobacco media campaigns, and Tobacco 21 laws implemented in the U.S. Outcomes include cigarette smoking initiation, prevalence, and cessation among youth and adults. Sources to be searched include Clarivate BIOSIS, EBSCO CINAHL Plus, Cochrane Library, Ovid MEDLINE, PsycINFO, Sociological Abstracts, Clarivate Web of Science Core Collection, and the National Bureau of Economic Research. Included studies must be written in English. Two independent reviewers will screen and analyze relevant articles and then extract data on participants, context, methods, and key findings. Studies will be assessed using the Joanna Briggs Institute critical appraisal checklists and presented in 2 reviews: 1 youth focused (aged

Purpose: We investigated whether pulmonary metastases from historically considered radioresistant primaries would have inferior local control after radiation therapy than those from nonradioresistant nonlung primaries, and whether higher biologically effective dose assuming alpha/beta=10 (BED10) would be associated with superior local control. Methods and Materials: We identified patients treated with radiation therapy for oligometastatic or oligoprogressive pulmonary disease to 1 to 5 lung metastases from nonlung primaries in 2013 to 2020 at a single health care system. Radioresistant primary cancers included colorectal carcinoma, endometrial carcinoma, renal cell carcinoma, melanoma, and sarcoma. Nonradioresistant primary cancers included breast, bladder, esophageal, pancreas, and head and neck carcinomas. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare local recurrence-free survival (LRFS), new metastasis-free survival, progression-free survival, and overall survival. Results: Among 114 patients, 73 had radioresistant primary cancers. The median total dose was 50 Gy (IQR, 50-54 Gy) and the median number of fractions was 5 (IQR, 3-5). Median follow-up time was 59.6 months. One of 41 (2.4%) patients with a nonradioresistant metastasis experienced local failure compared with 18 of 73 (24.7%) patients with radioresistant metastasis (log-rank P = .004). Among radioresistant metastases, 12 of 41 (29.2%) patients with colorectal carcinoma experienced local failure compared with 6 of 32 (18.8%) with other primaries (log-rank P = .018). BED10 ≥100 Gy was associated with decreased risk of local recurrence. On univariable analysis, BED10 ≥100 Gy (hazard ratio [HR], 0.263; 95% CI, 0.105-0.656; P = .004) was associated with higher LRFS, and colorectal primary (HR, 3.060; 95% CI, 1.204-7.777; P = .019) was associated with lower LRFS, though these were not statistically significant on multivariable analysis. Among colorectal primary patients, BED10 ≥100 Gy was associated with higher LRFS (HR, 0.266; 95% CI, 0.072-0.985; P = .047) on multivariable analysis. Conclusions: Local control after radiation therapy was encouraging for pulmonary metastases from most nonlung primaries, even for many of those classically considered to be radioresistant. Those from colorectal primaries may benefit from testing additional strategies, such as resection or systemic treatment concurrent with radiation.

There is strong interest in sustainable aviation fuels (SAF) to decarbonize aviation; however, local decision-makers will need to consider what additional incentives could stimulate SAF commercialization within their own jurisdictions. This study analyzed SAF production in Virginia, evaluating two biomass-to-energy platforms (gasification Fischer Tropsch [GFT] and pyrolysis) and two regionally abundant feedstocks (woody wastes and municipal solid wastes). A suite of open-access modeling tools were applied to possible SAF supply chains encompassing feedstock collection and transportation, conversion, and fuel upgrading and transport. Key modeling outputs were minimum product selling price (MPSP) ($/gallon) and life-cycle global warming potential (GWP) (g CO2eq/MJ). Results suggest that early SAF production via GFT will require local incentives of approximately $3.61 per gallon compared to $0.75 per gallon for pilot-scale pyrolysis. Location of production facility (by county) influences economic and environmental metrics but is not nearly as important as facility size (tonnes/year). Different formats of financial incentives (i.e., tax credits, loan forgiveness, etc.) offer markedly different reductions in SAF MPSP. Finally, under current federal incentives in the US, it is still more economically efficient to use pyrolysis (with higher GWP) than GFT (with lower GWP). Therefore, regional stakeholders will need to navigate the tradeoff between economic and environmental performances of these platforms. Though Virginia was used as a case study, the methodology is replicable for other jurisdictions, insofar it can be adapted for use in other locations without decision-makers having to completely build their own TEA models.

Background: As life expectancy improves for patients with dementia, the demand for mobility-improving surgeries such as total joint arthroplasty (TJA) will increase. There is little research on patients with dementia undergoing TJA, although dementia has been shown to be a risk factor for complications. The purpose of this study is to compare postoperative outcomes of patients with dementia undergoing TJA at 90 days, 2 years, and 5 years. Methods: The TriNetX database was retrospectively queried for all patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Patients were divided into cohorts by preoperative diagnosis of dementia and propensity score matched. The following outcomes were evaluated between groups at 90 days, 2 years, and 5 years postoperatively: revision, resection arthroplasty, closed reduction (THA only), femur fracture plating, and prosthetic joint infection. Readmission and manipulation under anesthesia (TKA only) were evaluated at 90 days postoperatively. Univariate and multivariate analyses were performed. Results: After matching, there were no differences in demographics or comorbidities between groups. TKA (odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.42-2.15, P < .001) and THA (OR = 2.17, 95% CI 1.92-2.45, P < .001) patients with dementia were more likely to be readmitted than patients without dementia. At 2 years (OR = 2.07, 95% CI 1.14-3.77, P = .015) and 5 years (OR = 2.14, 95% CI 1.32-3.48, P = .002) postoperatively, THA patients with dementia were more likely to have proximal femur fracture plating than patients without dementia. Conclusions: Patients undergoing THA with dementia had worse outcomes than patients undergoing THA without dementia and TKA with dementia. The overall rate of complications was low, and a diagnosis of dementia should not be an absolute contraindication to proceeding with TJA.

Lyme borreliosis (LB) is the most common tick–borne disease in Germany. Although the incidence of LB in Germany has been assessed in several studies, those studies either used data from statutory surveillance, which frequently underreport cases, or data from health claims databases, which may overestimate cases due to non–specific LB case definitions. Here, using a more specific case definition, we describe the incidence of medically–attended LB by disease manifestation, age group, and federal state for the period 2015–2019. Both inpatient and outpatient cases were analyzed from a claims database. To be eligible for inclusion, patients were required to have an LB specific ICD–10 GM diagnosis code plus an antibiotic prescription, and for disseminated manifestations, a laboratory test order additionally. LB cases were classified as erythema migrans (EM), or disseminated disease including Lyme arthritis (LA), Lyme neuroborreliosis (LNB), and all other disease manifestations (OTH). Between 2015 and 2019, the incidence of medically–attended LB cases ranged from 195.7/100,000 population per year (95% confidence interval [CI], 191.0 – 200.5) to 254.5/100,000 population per year (95% CI, 249.0 – 260.0) per year. The majority of cases (92.2%) were EM, while 2.8% presented as LA, 3.8% as LNB, and 1.2% as OTH. For both EM and disseminated disease, the incidence peaked in children aged 5–9 years and in older adults. By federal state, the incidence of medically–attended EM ranged from 74.4/100,000 population per year (95% CI, 71.9 – 77.0) per year in Hamburg, to 394.1/100,000 population per year (95% CI, 370.7 – 417.6) per year in Saxony, whereas for medically–attended disseminated disease, the highest incidence was in Thuringia, Saxony, and Bavaria (range: 22.0 [95% CI, 19.9 – 24.0] to 35.7 [95% CI, 34.7 – 36.7] per 100,000 population per year). This study comprehensively estimated the incidence of all manifestations of medically–attended LB and showed a high incidence of LB throughout Germany. Results from the study support performing epidemiological studies in all federal states to measure the burden of LB and to invest in public health interventions for prevention.

Summary: Targeting programmed cell death protein 1 (PD-1) is an important component of many immune checkpoint blockade (ICB) therapeutic approaches. However, ICB is not an efficacious strategy in a variety of cancer types, in part due to immunosuppressive metabolites in the tumor microenvironment. Here, we find that αPD-1-resistant cancer cells produce abundant itaconate (ITA) due to enhanced levels of aconitate decarboxylase (Acod1). Acod1 has an important role in the resistance to αPD-1, as decreasing Acod1 levels in αPD-1-resistant cancer cells can sensitize tumors to αPD-1 therapy. Mechanistically, cancer cells with high Acod1 inhibit the proliferation of naive CD8+ T cells through the secretion of inhibitory factors. Surprisingly, inhibition of CD8+ T cell proliferation is not dependent on the secretion of ITA but is instead a consequence of the release of small inhibitory peptides. Our study suggests that strategies to counter the activity of Acod1 in cancer cells may sensitize tumors to ICB therapy.

Question: What are the smallest worthwhile effects of nonsteroidal anti-inflammatory drugs (NSAIDs) for people with acute and chronic low back pain (LBP)? What is the smallest worthwhile effect of individualised exercise for people with chronic LBP compared with no intervention? Design: Benefit-harm trade-off study. Participants: Participants were recruited by advertisement on social media and included if they were English-speaking adults in Australia who had non-specific LBP. Outcome measure: Pain intensity. Results: A total of 116 people with acute LBP and 230 people with chronic LBP were recruited. For acute LBP, the smallest worthwhile effect of NSAIDs additional to no intervention was a 30% (IQR 10 to 40%) reduction in pain intensity. For chronic LBP, the smallest worthwhile effect of NSAIDs additional to no intervention was a 27.5% (IQR 10 to 50%) reduction in pain intensity. For chronic LBP, the smallest worthwhile effect of exercise additional to no intervention was a 20% (IQR 10 to 40%) reduction in pain intensity. There were small associations between baseline pain, duration of pain and level of exercise and the smallest worthwhile effect of NSAIDs for acute LBP. There were no other clear associations. Conclusions: For people with LBP, the smallest worthwhile effect of exercise and NSAIDs additional to no intervention is approximately a 20 to 30% reduction in pain. These results can inform the interpretation of the effects of NSAIDs and exercise in randomised trials and meta-analyses, incorporating consumers’ perspectives. Further research on comparisons between different interventions and on other core LBP outcomes may inform decision-making. Registration: OSF osf.io/3erjx/.

Ultra-High-Performance Concrete (UHPC) represents an exceptionally durable construction material distinguished by its notable strength, ductility, and durability. Previous investigations have demonstrated a limited exploration of UHPC containing basalt fiber and waste glass as a substitute for cement. Current study concentrates on assessing the impact of incorporating waste glass powder (WGP) in lieu of cement, on the workability, mechanical properties, and microstructural attributes of this composite. The substitution involved three distinct proportions of waste pozzolanic glass powder: 10%, 20%, and 30%, measured by weight. A substantial number of test specimens, exceeding one hundred, was accurately prepared to inspect the engineering characteristics of five varied UHPC formulations. Experimental outcomes underline that the optimum UHPC compressive strength was recorded at the 28-day when employing a 0.75% basalt fiber content and replacing 20% of cement with waste glass. This investigation establishes the distinctive contribution of WGP pozzolanic constituents in enhancing the microstructure of UHPC.

Aminophospholipids (aPL) such as phosphatidylserine are essential for supporting the activity of coagulation factors, circulating platelets, and blood cells. Phosphatidylthreonine (PT) is an aminophospholipid previously reported in eukaryotic parasites and animal cell cultures, but not yet in human tissues. Here, we evaluated whether PT is present in blood cells and characterized its ability to support coagulation. Several PT molecular species were detected in human blood, washed platelets, extracellular vesicles, and isolated leukocytes from healthy volunteers using liquid chromatography–tandem mass spectrometry. The ability of PT to support coagulation was demonstrated in vitro using biochemical and biophysical assays. In liposomes, PT supported prothrombinase activity in the presence and absence of phosphatidylserine. PT nanodiscs strongly bound FVa and lactadherin (nM affinity) but poorly bound prothrombin and FX, suggesting that PT supports prothrombinase through recruitment of FVa. PT liposomes bearing tissue factor poorly generated thrombin in platelet poor plasma, indicating that PT poorly supports extrinsic tenase activity. On platelet activation, PT is externalized and partially metabolized. Last, PT was significantly higher in platelets and extracellular vesicle from patients with coronary artery disease than in healthy controls. In summary, PT is present in human blood, binds FVa and lactadherin, supports coagulation in vitro through FVa binding, and is elevated in atherosclerotic vascular disease. Our studies reveal a new phospholipid subclass, that contributes to the procoagulant membrane, and may support thrombosis in patients at elevated risk.

Recalcitrance and the inherent heterogeneity of lignin structure are the major bottlenecks to impede the popularization of lignin-based chemicals production processes. Recent works suggested a promising pathway for lignin depolymerization and lignin-derived bio-oil upgrading via an electrochemical biorefinery (a process in which lignin valorization is performed via electrochemical oxidation or reduction). This review presents the progress on chemicals synthesis and bio-oil upgrading from lignin by an electrochemical biorefinery, relating to the lignin biosynthesis pathway, reaction pathway of lignin electrochemical conversion, inner-sphere and outer-sphere electron transfer mechanism, basic kinetics and thermodynamics in electrochemistry, and the recent embodiments analysis with the emphasis on the respective feature and limitation for lignin electrochemical oxidative and reductive conversion. Lastly, the challenge and perspective associated with lignin electrochemical biorefinery are discussed. Present-day results indicate that more work should be performed to promote efficiency, selectivity, and stability in pursuing a lignin electrochemical biorefinery. One of the most promising developing directions appears to be integrating various types of lignin electrochemical conversion strategies and other existing or evolving lignin valorization technologies. This review aims to provide more references and discussion on the development for lignin electrochemical biorefinery.

One of the most common errors in intraoperative medication delivery is the result of “syringe swap,” when syringes that have been mixed up lead to the incorrect administration of a drug. An improvement of syringe organization could reduce medication administration errors. Recently, there have been many efforts to improve medication organization; however, these interventions struggle to achieve widespread use, even though they typically report substantial improvements in error rates and medication awareness in home institutions.A syringe organization hub was developed based on observations, interviews, and past designs. In order to assess the perceived acceptance of the hub, we used the Technology Acceptance Model (TAM) to develop a survey that was distributed to anesthesia providers at two medical institutions in the United States: one in the Mid-Atlantic and one in the southeast.The results of the four different linear regression models revealed that participants at the southeastern institution had significantly lower usefulness ratings (p

Diffuse reflectance spectroscopy has been extensively employed to deliver timely and cost-effective predictions of a number of soil properties. However, although several soil spectral laboratories have been established worldwide, the distinct characteristics of instruments and operations still hamper further integration and interoperability across mid-infrared (MIR) soil spectral libraries. In this study, we conducted a large-scale ring trial experiment to understand the lab-to-lab variability of multiple MIR instruments. By developing a systematic evaluation of different mathematical treatments with modeling algorithms, including regular preprocessing and spectral standardization, we quantified and evaluated instruments' dissimilarity and how this impacts internal and shared model performance. We found that all instruments delivered good predictions when calibrated internally using the same instruments' characteristics and standard operating procedures by solely relying on regular spectral preprocessing that accounts for light scattering and multiplicative/additive effects, e.g., using standard normal variate (SNV). When performing model transfer from a large public library (the USDA NSSC-KSSL MIR library) to secondary instruments, good performance was also achieved by regular preprocessing (e.g., SNV) if both instruments shared the same manufacturer. However, significant differences between the KSSL MIR library and contrasting ring trial instruments responses were evident and confirmed by a semi-unsupervised spectral clustering. For heavily contrasting setups, spectral standardization was necessary before transferring prediction models. Non-linear model types like Cubist and memory-based learning delivered more precise estimates because they seemed to be less sensitive to spectral variations than global partial least square regression. In summary, the results from this study can assist new laboratories in building spectroscopy capacity utilizing existing MIR spectral libraries and support the recent global efforts to make soil spectroscopy universally accessible with centralized or shared operating procedures.

An individual's brain predicted age minus chronological age (brain-PAD) obtained from MRIs could become a biomarker of disease in research studies. However, brain age reports from clinical MRIs are scant despite the rich clinical information hospitals provide. Since clinical MRI protocols are meant for specific clinical purposes, performance of brain age predictions on clinical data need to be tested. We explored the feasibility of using DeepBrainNet, a deep network previously trained on research-oriented MRIs, to predict the brain ages of 840 patients who visited 15 facilities of a health system in Florida. Anticipating a strong prediction bias in our clinical sample, we characterized it to propose a covariate model in group-level regressions of brain-PAD (recommended to avoid Type I, II errors), and tested its generalizability, a requirement for meaningful brain age predictions in new single clinical cases. The best bias-related covariate model was scanner-independent and linear in age, while the best method to estimate bias-free brain ages was the inverse of a scanner-independent and quadratic in brain age function. We demonstrated the feasibility to detect sex-related differences in brain-PAD using group-level regression accounting for the selected covariate model. These differences were preserved after bias correction. The Mean-Average Error (MAE) of the predictions in independent data was ∼8 years, 2–3 years greater than reports for research-oriented MRIs using DeepBrainNet, whereas an R2 (assuming no bias) was 0.33 and 0.76 for the uncorrected and corrected brain ages, respectively. DeepBrainNet on clinical populations seems feasible, but more accurate algorithms or transfer-learning retraining is needed.

Study region: The Morava River basin, Czech Republic, Danube Basin, Central Europe. Study focus: Hydrological summer extremes represent a prominent natural hazard in Central Europe. River low flows constrain transport and water supply for agriculture, industry and society, and flood events are known to cause material damage and human loss. However, understanding changes in the frequency and magnitude of hydrological extremes is associated with great uncertainty due to the limited number of gauge observations. Here, we compile a tree-ring network to reconstruct the July–September baseflow variability of the Morava River from 1745 to 2018 CE. An ensemble of reconstructions was produced to assess the impact of calibration period length and trend on the long-term mean of reconstruction estimates. The final estimates represent the first baseflow reconstruction based on tree rings from the European continent. Simulated flows and historical documentation provide quantitative and qualitative validation of estimates prior to the 20th century. New hydrological insights for the region: The reconstructions indicate an increased variability of warm-season flow during the past 100 years, with the most extreme high and low flows occurring after the start of instrumental observations. When analyzing the entire reconstruction, the negative trend in baseflow displayed by gauges across the basin after 1960 is not unprecedented. We conjecture that even lower flows could likely occur in the future considering that pre-instrumental trends were not primarily driven by rising temperature (and the evaporative demand) in contrast to the recent trends.

Rationale & Objective: Heart failure (HF) is an important cause of morbidity and mortality among individuals with chronic kidney disease (CKD). A large body of evidence from preclinical and clinical studies implicates excess levels of fibroblast growth factor 23 (FGF23) in HF pathogenesis in CKD. It remains unclear whether the relationship between elevated FGF23 levels and HF risk among individuals with CKD varies by HF subtype. Study Design: Prospective cohort study. Settings & Participants: A total of 3,502 participants were selected in the Chronic Renal Insufficiency Cohort study. Exposure: Baseline plasma FGF23. Outcomes: Incident HF by subtype and total rate of HF hospitalization. HF was categorized as HF with preserved ejection fraction (HFpEF, ejection fraction [EF] ≥ 50%), HF with reduced EF (HFrEF, EF

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.