The Last (Koy-Yukon) Interglaciation in the Northern Yukon: Evidence from Unit 4 at Ch’ijee’s Bluff, Bluefish Basin

The effects of predicted anthropogenic warming can be assessed in part by documenting responses to past warming events. One of the most pronounced warmings was the last interglaciation - stage 5 of the marine isotope record. A large multinational and multidisciplinary project (CELIA) was launched recently in order to gain detailed knowledge of the climate during stage 5. Several key exposures were identified by CELIA; one of them is Ch'ijee's Bluff on the Porcupine River, northern Yukon. Pollen, plant and insect macrofossils and stratigraphie evidence from Ch'ijee's Bluff show that the part of Ch'ijee's Unit 4 that is above and younger than Old Crow tephra (OCt) was deposited during an interval of climate warmer than present. When OCt was dated at 85 ka BP, the subsequent warming interval was presumed to be correlative with the early part of marine isotope stage 3. New dates on OCt show it to be 140-150 ka BP, and this means that the warm interval discussed here is more likely of stage 5 than stage 3 age. We apply the informal epithet, "Koy-Yukon interglaciation", to it and compare the Ch'ijee's Bluff Unit 4 sequence with other east Beringian sites that contain both Old Crow tephra and putative interglacial deposits.Les conséquences du réchauffement anthropique attendu pourraient en partie être évaluées à partir de nos connaissances sur les réchauffements climatiques antérieurs. Le réchauffement climatique le plus important s'est produit au cours du dernier interglaciaire (stade isotopique 5). Dans le but d'acquérir une meilleure connaissance du climat durant le stade 5, on a créé un important projet multidisciplinaire et multinational (CELIA). On a identifié plusieurs coupes clés dont celle de Ch'ijee's Bluff, de la Porcupine River, dans le nord du Yukon. Les indices fournis par le pollen, les végétaux, les macrofossiles d'insectes et la stratigraphie de Ch'ijee's Bluff démontrent que la partie de l'unité n 4 plus jeune que le tephra de Old Crow et située au-dessus a été déposée durant un intervalle plus chaud qu'aujourd'hui. Quand on a daté à 85 ka BP le tephra de Old Crow, on présumait que l'intervalle de réchauffement subséquent était corrélatif au stade isotopique 3, Les nouvelles dates le font maintenant remonter à 140-150 ka BP, ce qui signifie que le réchauffement climatique appartient plutôt au stade 5. On lui a attribué le nom informel de « interglaciaire de Koy-Yukon ». On a comparé la séquence de l'unité n 4 avec celle d'autres sites de Béringie qui renferment à la fois le tephra de Old Crow et des dépôts considérés comme étant interglaciaires.Die Auswirkungen einer erwarteten anthropogenen Erwàrmung kann man teilweise abschâtzen, indem man die Ergebnisse vergangener klimatischer Erwârmungen dokumentiert. Eine der herausragendsten klimatischen Erwârmungen war die letzte Interglazialzeit - Stadium 5 des marinen Isotop-Belegs. Kùrzlich hat man ein breitangelegtes multinationales und multidisziplinàres Projekt (CELIA) gestartet, um detaillierte Kenntnis ùber das Klima wàhrend des Stadium 5 zu erhalten. CELIA hat mehrere Schlussel-Schnitte identifiziert; einer davon ist Ch'ijee's Bluff am Porcupine River, nôrdliches Yukon. Die von Pollen, Pflanzen, Insektenmakrofossilen und Stratigraphie von Ch'ijee's Bluff gelieferten Anhaltspunkte zeigen, dass der Teil der Ch'ijee's-Einheit 4, der ùber Old Crow Tephra (OCt) liegt und jùnger ist, wâhrend eines klimatischen Intervalls. das warmer war als gengewârtig, abgelagert wurde. AIs man OCt auf 85 ka v. u. Z. datierte. nahm man an. dass das folgende Erwàrmungs-lntervall mit dem frùhen Teil des marinen Isotop-Stadiums 3 korrelierte. Neue Daten auf OCt zeigen, dass dieses 140-150 ka v. u. Z. ait ist, und das bedeutet, dass das warme Intervall, von dem hier die Rede ist. wohl eher dem Stadium 5 als dem Stadium 3 zugehôrt. Wir benutzen die informelle Bezeichnung "Koy-Yukon Interglazialzeit" und vergleichen die Ch'ijee's Bluff 4-Sequenz mit anderen Plâtzen von Ost-Bering, die sowohl Old Crow Tephra enthalten wie auch Ablagerungen, die man fur interglaziale Ablagerungen hait

Brand and generic use of inhalation medication and frequency of switching in children and adults : a population-based cohort study

BACKGROUND: The expiration of patents of brand inhalation medications and the ongoing pressure on healthcare budgets resulted in a growing market for generics. AIM: To study the use of brand and generic inhalation medication and the frequency of switching between brand and generic and between devices. In addition, we investigated whether switching affected adherence. METHODS: From dispensing data from the Dutch PHARMO Database Network a cohort aged ≥ 5 years, using ≥ 1 year of inhalation medication between 2003 and 2012 was selected. Switching was defined as changing from brand to generic or vice versa. In addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and nebulizers). Adherence was calculated using the medication possession ratio (MPR). RESULTS: The total cohort comprised 70,053 patients with 1,604,488 dispensations. Per calendar year, 5% switched between brand and generic inhalation medication and 5% switched between devices. Median MPRs over the first 12 months ranged between 33 and 55%. Median MPR over the total period was lower after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1 and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9). CONCLUSION: Per year, switching between brand and generic inhalation medication was limited to 5% of the patients, switching between device types was observed in 5% as well. Adherence to both generic and brand inhalation medication was low. Effect of switching on adherence was contradictory; depending on time period, medication and type, and direction of switching. Further research on reasons for switching and potential impact on clinical outcomes is warranted

Усовершенствование механизмов обеспечения производственной безопасности при бурении скважин

Объектом исследования является производственная безопасность при бурении скважин. Цель работы – усовершенствование механизмов обеспечения производственной безопасности при бурении скважин. Предмет исследования – механизмы обеспечения производственной безопасности при бурении скважин. В процессе исследования были изучены общие требования безопасности на объектах бурения, рассматривалась система производственной безопасности в ООО "СГК-Бурение", был проведен анализ состояния несчастных случаев при бурении скважин (по состоянию с 2014 по 2018 гг.) и выявлены основные их причины. Были раскрыты механизмы обеспечения производственной безопасности на объектах бурения.The object of the study is production safety when drilling wells. The purpose of the work is to improve the mechanisms of ensuring production safety while drilling wells. The subject of the study is the mechanisms for ensuring production safety while drilling wells. In the course of the study, general safety requirements for drilling sites were studied, the production safety system at LLC "SGC-Burenie" was considered, an analysis of the state of accidents during drilling of wells (as from 2014 to 2018) was carried out and their main causes were identified. The mechanisms for ensuring production safety at drilling facilities were disclosed

Biomarkers to assess right heart pressures in recipients of a heart transplant: a proof-of-concept study

Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients. Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments. Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 (P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy (P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement. Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered

Reactivity of Cobalt-Fullerene Complexes towards Deuterium

The adsorption of molecular deuterium (D2) onto charged cobalt-fullerene-complexes ConC60 + (n=1–8) is measured experimentally in a few-collision reaction cell. The reactivity is strongly size-dependent, hinting at clustering of the transition metal atoms on the fullerenes. Formation and desorption rate constants are obtained from the pressure-dependent deuterogenation curves. DFT calculations indeed find that this transition metal clustering is energetically more favorable than decorating the fullerene. For n=1, D2 is predicted to bind molecularly and for n=2 dissociative and molecular configurations are quasi-isoenergetic. For n=3–8, dissociation of D2 is thermodynamically preferred. However, reaching the ground state configuration with dissociated deuterium on the timescale of the experiment may be hindered by dissociation barriers.Fil: Vanbuel, Jan. Katholikie Universiteit Leuven; BélgicaFil: German, Estefania. Universidad de Valladolid; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Libeert, Guillaume. Katholikie Universiteit Leuven; BélgicaFil: Veys, Koen. Katholikie Universiteit Leuven; BélgicaFil: Moens, Janni. Katholikie Universiteit Leuven; BélgicaFil: Alonso, Julio A.. Donostia International Physics Center; España. Universidad de Valladolid; EspañaFil: López, María J.. Universidad de Valladolid; EspañaFil: Janssens, Ewald. Katholikie Universiteit Leuven; Bélgic

Soil and irrigation water management : farmer’s practice, insight, and major constraints in Upper Blue Nile Basin, Ethiopia

This study assessed farmers’ soil and irrigation water management practices, perceptions, and major constraints at Koga, a large-scale irrigation scheme in Ethiopia. Key informant interviews, structured and semi-structured questionnaires, focus group discussions, and field visits were used for data collection. Soil samples were collected for the assessment of soil properties and a comparison with the respondents’ perception of soil-related constraints. A total of 385 respondents were involved in the questionnaire. All of the respondents had a good perception of soil acidity and its management strategies. Respondents’ perception was in line with the mean soil pH, soil texture, infiltration rate, exchangeable acidity, and soil organic carbon obtained from lab analysis and field tests. Soil acidity, unwise use of water, water scarcity, and lack of market linkages hampered the performance of the Koga irrigation scheme. Yet, respondents had a low awareness of irrigation water management. Farmers never used irrigation scheduling, but apply the same amount of water regardless of the crop type. As a result, low yield and water use efficiency were reported. To reduce soil acidity, an adequate lime supply for farmers with hands-on training on how to apply it would be desirable. Farmers should be aware of how to design effective irrigation scheduling and adopt water-saving management strategies

Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence.

BACKGROUND: The structure-specific ERCC1/XPF endonuclease complex that contains the ERCC1 and XPF subunits is implicated in the repair of two distinct types of lesions in DNA: nucleotide excision repair (NER) for ultraviolet-induced lesions and bulky chemical adducts; and recombination repair of the very genotoxic interstrand cross-links. RESULTS: Here, we present a detailed analysis of two types of mice with mutations in ERCC1, one in which the gene is 'knocked out', and one in which the encoded protein contains a seven amino-acid carboxy-terminal truncation. In addition to the previously reported symptoms of severe runting, abnormalities of liver nuclei and greatly reduced lifespan (which appeared less severe in the truncation mutant), both types of ERCC1-mutant mouse exhibited an absence of subcutaneous fat, early onset of ferritin deposition in the spleen, kidney malfunction, gross abnormalities of ploidy and cytoplasmic invaginations in nuclei of liver and kidney, and compromised NER and cross-link repair. We also found that heterozygosity for ERCC1 mutations did not appear to provide a selective advantage for chemically induced tumorigenesis. An important clue to the cause of the very severe ERCC1-mutant phenotypes is our finding that ERCC1-mutant cells undergo premature replicative senescence, unlike cells from mice with a defect only in NER. CONCLUSIONS: Our results strongly suggest that the accumulation in ERCC1-mutant mice of endogenously generated DNA interstrand cross-links, which are normally repaired by ERCC1-dependent recombination repair, underlies both the early onset of cell cycle arrest and polyploidy in the liver and kidney. Thus, our work provides an insight into the molecular basis of ageing and highlights the role of ERCC1 and interstrand DNA cross-links

Urinary Proteomic Profile of Arterial Stiffness Is Associated With Mortality and Cardiovascular Outcomes

Background The underlying mechanisms of arterial stiffness remain not fully understood. This study aimed to identify a urinary proteomic profile to illuminate its pathogenesis and to determine the prognostic value of the profile for adverse outcomes. Methods and Results We measured aortic stiffness using pulse wave velocity (PWV) and analyzed urinary proteome using capillary electrophoresis coupled with mass spectrometry in 669 randomly recruited Flemish patients (mean age, 50.2 years; 51.1% women). We developed a PWV‐derived urinary proteomic score (PWV‐UP) by modeling PWV with proteomics data at baseline through orthogonal projections to latent structures. PWV‐UP that consisted of 2336 peptides explained the 65% variance of PWV, higher than 36% explained by clinical risk factors. PWV‐UP was significantly associated with PWV (adjusted β=0.73 [95% CI, 0.67–0.79]; P\u3c0.0001). Over 9.2 years (median), 36 participants died, and 75 experienced cardiovascular events. The adjusted hazard ratios (+1 SD) were 1.46 (95% CI, 1.08–1.97) for all‐cause mortality, 2.04 (95% CI, 1.07–3.87) for cardiovascular mortality, and 1.39 (95% CI, 1.11–1.74) for cardiovascular events (P≤0.031). For PWV, the corresponding estimates were 1.25 (95% CI, 0.97–1.60), 1.35 (95% CI, 0.85–2.15), and 1.22 (95% CI, 1.02–1.47), respectively (P≥0.033). Pathway analysis revealed that the peptides in PWV‐UP mostly involved multiple pathways, including collagen turnover, cell adhesion, inflammation, and lipid metabolism. Conclusions PWV‐UP was highly associated with PWV and could be used as a biomarker of arterial stiffness. PWV‐UP, but not PWV, was associated with all‐cause mortality and cardiovascular mortality, implying that PWV‐UP–associated peptides may be multifaceted and involved in diverse pathological processes beyond arterial stiffness

Effect of 24-h blood pressure dysregulations and reduced ocular perfusion pressure in open-angle glaucoma progression

Background: Low ocular perfusion pressure (OPP), which depends on the mean arterial pressure (MAP) and intraocular pressure (IOP), is associated with glaucoma. We studied 24-h MAP dysregulations and OPP in relation to the progression of glaucoma damage. Methods: We retrospectively analyzed 155 normal-tension glaucoma (NTG) and 110 primary open-angle glaucoma (POAG) patients aged 18 years old followed at the University Hospital Leuven with repeated visual field tests (n = 7000 measures, including both eyes) who underwent 24-h ambulatory blood pressure monitoring. Twenty-four-hour MAP dysregulations were variability independent of the mean (VIM), and the five lowest dips in MAP readings over 24 h. OPP was the difference between 2/3 of the MAP and IOP. Glaucoma progression was the deterioration of the visual field, expressed as decibel (dB) changes in mean deviation analyzed by applying multivariable linear mixed regression models. Results: The mean age was 68 years (53% were women). High 24-h VIMmap was associated with glaucoma progression in POAG (P \u3c 0.001) independently of the 24-h MAP level. The estimated changes in mean deviation in relation to dip MAP measures ranged from −2.84 dB [95% confidence interval (CI) −4.12 to −1.57] to −2.16 dB (95% CI −3.46 to −0.85) in POAG. Reduced OPP along with high variability and dips in MAP resulted in worse mean deviation deterioration. Conclusion: The progression of glaucoma damage associates with repetitive and extreme dips in MAP caused by high variability in MAP throughout 24 h. This progression exacerbates if 24-h MAP dysregulations occur along with reduced OPP

Copper-Heparin Inhalation Therapy To Repair Emphysema:A Scientific Rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration