Prognostic Value of Multidetector Coronary Computed Tomographic Angiography for Prediction of All-Cause Mortality James K. Min, Leslee J. Shaw, Richard B. Devereux, Peter M. Okin, Jonathan W. ...Weinsaft, Donald J. Russo, Nicholas J. Lippolis, Daniel S. Berman, Tracy Q. Callister This study examined the prediction of death from all-causes by the results of coronary computed tomographic angiography (CCTA). The CCTA measurements predictive of death included severity of stenosis in the proximal left anterior descending artery (p = 0.001) and the extent of coronary artery disease (CAD) by the number of vessels with ≥50% stenosis (p < 0.0001) and ≥70% stenosis (p < 0.0001). A modified Duke prognostic CAD index, a previously validated angiographic score integrating proximal disease, disease extent, and left main disease, improved stratification of death (p < 0.0001). In patients presenting with chest pain, CCTA identifies individuals at increased risk for all-cause death. Importantly, a negative CCTA portends an extremely low risk for death.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recovery of cognitive and physiological responses following a hypoxic exposure may not be considered in various operational and research settings. Understanding recovery profiles and influential ...factors can guide post-hypoxia restrictions to reduce the risk of further cognitive and physiological deterioration, and the potential for incidents and accidents. We systematically evaluated the available evidence on recovery of cognitive and basic physiological responses following an acute hypoxic exposure to improve understanding of the performance and safety implications, and to inform post-hypoxia restrictions. This systematic review summarises 30 studies that document the recovery of either a cognitive or physiological index from an acute hypoxic exposure. Titles and abstracts from PubMed (MEDLINE) and Scopus were searched from inception to July 2022, of which 22 full text articles were considered eligible. An additional 8 articles from other sources were identified and also considered eligible. The overall quality of evidence was moderate (average Rosendal score, 58%) and there was a large range of hypoxic exposures. Heart rate, peripheral blood haemoglobin-oxygen saturation and heart rate variability typically normalised within seconds-to-minutes following return to normoxia or hyperoxia. Whereas, cognitive performance, blood pressure, cerebral tissue oxygenation, ventilation and electroencephalogram indices could persist for minutes-to-hours following a hypoxic exposure, and one study suggested regional cerebral tissue oxygenation requires up to 24 hours to recover. Full recovery of most cognitive and physiological indices, however, appear much sooner and typically within ~2–4 hours. Based on these findings, there is evidence to support a ‘hypoxia hangover’ and a need to implement restrictions following acute hypoxic exposures. The severity and duration of these restrictions is unclear but should consider the population, subsequent requirement for safety-critical tasks and hypoxic exposure.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, ...origin and stability of this mutation in ALS+/-FTD from five European cohorts (total n=1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n=434) and controls (n=856). Haplotypes were analysed using PLINK and aged using DMLE+. In a London clinic cohort, the HREM was the most common mutation in familial ALS+/-FTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS+/-FTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, P<10(-8)). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe.
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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
Nature provides a wide range of benefits to people. There is increasing consensus about the importance of incorporating these âecosystem servicesâ into resource management decisions, but ...quantifying the levels and values of these services has proven difficult. We use a spatially explicit modeling tool, Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST), to predict changes in ecosystem services, biodiversity conservation, and commodity production levels. We apply InVEST to stakeholderâdefined scenarios of landâuse/landâcover change in the Willamette Basin, Oregon. We found that scenarios that received high scores for a variety of ecosystem services also had high scores for biodiversity, suggesting there is little tradeoff between biodiversity conservation and ecosystem services. Scenarios involving more development had higher commodity production values, but lower levels of biodiversity conservation and ecosystem services. However, including payments for carbon sequestration alleviates this tradeoff. Quantifying ecosystem services in a spatially explicit manner, and analyzing tradeoffs between them, can help to make natural resource decisions more effective, efficient, and defensible.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Pesticides containing lead and arsenic were widely used in the US through the 20th century. Legacy contamination from this use poses a health risk as interest in cultivation of abandoned agricultural ...lands has grown in recent years. We addressed these risks by quantifying Pb and As in soils and produce from a suburban farm in New Jersey, USA and examining the ability of phosphate-bearing amendments (bone meal, triple super phosphate, manure compost and raised bed soil) in combination with Fe and/or Mn amendments to stabilize these metals and prevent their movement into vegetables. Common produce (tomato, carrot, lettuce, and radish) was grown in soils with 133–307 mg Pb kg−1 and 19–73 mg As kg−1. Our results suggest that vegetables produced on these soils can have Pb and As at levels above health and safety standards, especially root and leafy green vegetables. Phosphate-bearing amendments can reduce extractable Pb but can increase extractable As in soils, and can have similar effects on vegetables. Iron amendment increased both extractable Pb and As, likely due to the presence of elemental sulfur in the Fe amendment, which lowered soil pH, while Mn amendment had the opposite effect. Most of the Pb and As in vegetables appear to be associated with soil particles adhered to the vegetables, and the contribution from uptake was relatively small except for plots treated with Fe-amendments and for carrots. Thus, proper crop selection, rigorous cleaning, and dust and dirt control are critical to reduce the risk of contaminant exposure through the consumption of garden produce.
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•Soils can have elevated Pb and As due to past pesticide use.•Vegetables produced on these soils can have metals levels above safety standards.•Addition of P stabilizes Pb and mobilizes As.•Root and green leafy vegetables had the highest Pb/As due to soil particle adherence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Hyperoxic breathing is used by various populations, including the military.•Hyperoxic breathing appears to enhance aspects of cognitive performance.•Studies investigating hyperoxia on cognition are ...limited and of poor quality.•The magnitude of potential benefits is unreliable due to high study heterogeneity.
This systematic review, meta-analysis and meta-regression examined the effect of acute normobaric hyperoxic breathing on cognition in healthy humans. 23 studies were included providing 76 effect estimates (EE). Hyperoxic breathing improved memory accuracy (22 EEs; g = 0.34) and speed (9 EEs; g = 0.59), attention accuracy (7 EEs; g = 0.59) and speed (7 EEs; g = 0.51), reaction speed (8 EEs; g = 0.82), crystallised intelligence (7 EEs; g = 0.73), executive function (6 EEs; g = 0.88) and information processing (10 EEs; g = 0.62). However, the overall quality of evidence was low (average Rosendal score of 47%) and there was a large range of study heterogeneity, with prediction intervals often crossing 0; therefore, reducing the reliability of the magnitude of these favourable effects. Oxygen percentage, 100% compared with 22–99% oxygen, temporal position of administration to task performance, and study quality did not influence the overall weighted mean effects for most cognitive domains. Altogether, despite beneficial results, further high quality research is required prior to recommending hyperoxic breathing to enhance cognition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In a phase 1–2 dose-escalation trial involving adults with ALS due to
SOD1
mutations who received intrathecal tofersen (an antisense oligonucleotide) or placebo, the levels of mutant SOD1 in the CSF ...were 33 percentage points lower in the highest-dose tofersen group than in the placebo group.
To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), ...neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6h of injury, and between 12 and 36h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6h of injury, and between 6 and 12h, all AUCs except AP were between 0.68 and 0.78. Beyond 12h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We tested the hypothesis that ingestion of cocoa flavanols would improve cognition during acute hypoxia equivalent to 5,500 m altitude (partial pressure of end-tidal oxygen = 45 mmHg). Using ...placebo-controlled double-blind trials, 12 participants ingested 15 mg·kg
of cocoa flavanols 90 min before completing cognitive tasks during normoxia and either poikilocapnic or isocapnic hypoxia (partial pressure of end-tidal carbon dioxide uncontrolled or maintained at the baseline value, respectively). Cerebral oxygenation was measured using functional near-infrared spectroscopy. Overall cognition was impaired by poikilocapnic hypoxia (main effect of hypoxia,
= 0.008). Cocoa flavanols improved a measure of overall cognitive performance by 4% compared with placebo (effect of flavanols,
= 0.033) during hypoxia, indicating a change in performance from "low average" to "average." The hypoxia-induced decrease in cerebral oxygenation was two-fold greater with placebo than with cocoa flavanols (effect of flavanols,
= 0.005). Subjective fatigue was increased by 900% with placebo compared with flavanols during poikilocapnic hypoxia (effect of flavanols,
= 0.004). Overall cognition was impaired by isocapnic hypoxia (effect of hypoxia,
= 0.001) but was not improved by cocoa flavanols (mean improvement = 1%; effect of flavanols,
= 0.72). Reaction time was impaired by 8% with flavanols during normoxia and further impaired by 11% during isocapnic hypoxia (effect of flavanols,
= 0.01). Our findings are the first to show that flavanol-mediated improvements in cognition and mood during normoxia persist during severe oxygen deprivation, conferring a neuroprotective effect.
We show for the first time that cocoa flavanols exert a neuroprotective effect during severe hypoxia. Following acute cocoa flavanol ingestion, we observed improvements in cognition, cerebral oxygenation, and subjective fatigue during normoxia and severe poikilocapnic hypoxia. Cocoa flavanols did not improve cognition during severe isocapnic hypoxia, suggesting a possible interaction with carbon dioxide.
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