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In this randomized, controlled trial involving neonates in two Australian tertiary neonatal intensive care units, nasal high-flow therapy during neonatal endotracheal intubation increased the likelihood of successful intubation on the first attempt without physiological instability.

The global biosphere is commonly assumed to have been less productive before the rise of complex eukaryotic ecosystems than it is today 1 . However, direct evidence for this assertion is lacking. Here we present triple oxygen isotope measurements (∆ 17 O) from sedimentary sulfates from the Sibley basin (Ontario, Canada) dated to about 1.4 billion years ago, which provide evidence for a less productive biosphere in the middle of the Proterozoic eon. We report what are, to our knowledge, the most-negative ∆ 17 O values (down to −0.88‰) observed in sulfates, except for those from the terminal Cryogenian period 2 . This observation demonstrates that the mid-Proterozoic atmosphere was distinct from what persisted over approximately the past 0.5 billion years, directly reflecting a unique interplay among the atmospheric partial pressures of CO 2 and O 2 and the photosynthetic O 2 flux at this time 3 . Oxygenic gross primary productivity is stoichiometrically related to the photosynthetic O 2 flux to the atmosphere. Under current estimates of mid-Proterozoic atmospheric partial pressure of CO 2 (2–30 times that of pre-anthropogenic levels), our modelling indicates that gross primary productivity was between about 6% and 41% of pre-anthropogenic levels if atmospheric O 2 was between 0.1–1% or 1–10% of pre-anthropogenic levels, respectively. When compared to estimates of Archaean 4 – 6 and Phanerozoic primary production 7 , these model solutions show that an increasingly more productive biosphere accompanied the broad secular pattern of increasing atmospheric O 2 over geologic time 8 . Triple oxygen isotope measurements of 1.4-billion-year-old sedimentary sulfates reveal a unique mid-Proterozoic atmosphere and demonstrate that gross primary productivity in the mid-Proterozoic was between 6% and 41% of pre-anthropogenic levels.

Maximal oxygen uptake ([Formula: see text]) is a measure of cardiorespiratory fitness often used to monitor changes in fitness during and after treatment in cancer patients. There is, however, limited knowledge in how criteria verifying [Formula: see text] work for patients newly diagnosed with cancer. Therefore, the aim of this study was to describe the prevalence of fulfillment of typical criteria verifying [Formula: see text] and to investigate the associations between the criteria and the test leader's evaluation whether a test was performed \"to exhaustion\". An additional aim was to establish new cut-points within the associated criteria. From the Phys-Can randomized controlled trial, 535 patients (59 ±12 years) newly diagnosed with breast (79%), prostate (17%) or colorectal cancer (4%) performed an incremental [Formula: see text] test on a treadmill. The test was performed before starting (neo-)adjuvant treatment and an exercise intervention. Fulfillment of different cut-points within typical criteria verifying [Formula: see text] was described. The dependent key variables included in the initial bivariate analysis were achievement of a [Formula: see text] plateau, peak values for maximal heart rate, respiratory exchange ratio (RER), the patients' rating of perceived exertion on Borg's scale6-20 and peak breathing frequency (fR). A receiver operating characteristic analysis was performed to establish cut-points for variables associated with the test leader's evaluation. Last, a cross-validation of the cut-points found in the receiver operating characteristic analysis was performed on a comparable sample of cancer patients (n = 80). The criteria RERpeak (<0.001), Borg's RPE (<0.001) and fR peak (p = 0.018) were associated with the test leader's evaluation of whether a test was defined as \"to exhaustion\". The cut-points that best predicted the test leader's evaluation were RER ≥ 1.14, RPE ≥ 18 and fR ≥ 40. Maximal heart rate and [Formula: see text] plateau was not associated with the test leader's evaluation. We recommend a focus on RER (in the range between ≥1.1 and ≥1.15) and RPE (≥17 or ≥18) in addition to the test leader's evaluation. Additionally, a fR peak of ≥40 breaths/min may be a cut-point to help the test leader evaluate the degree of exhaustion. However, more research is needed to verify our findings, and to investigate how these criteria will work within a population that are undergoing or finished with cancer treatment.

To assess the role of high-flow nasal therapy (HFNT) compared to standard oxygen (SO) as complementary therapy to non-invasive ventilation (NIV). Multicenter trial including patients (n = 54) anticipated to receive NIV for ≥24 h due to acute or acute-on-chronic respiratory failure. Subjects were randomized (1:1) to SO or HFNT during breaks off NIV. Primary outcome was total time on and off NIV. Secondary outcomes were comfort and dyspnea, respiratory rate (RR), oxygen saturation (SpO2), tolerance and side effects. Total time per patient on NIV (1315 vs 1441 min) and breaks (1362 vs 1196 min), and mean duration of each break (520 vs 370 min) were similar in the HFNT and SO arms (p > .05). Comfort score was higher on HFNT than on SO (8.3 ± 2.7 vs 6.9 ± 2.3, p = .001). Dyspnea, RR and SpO2 were similar in the two arms, but the increase in RR and dyspnea seen with SO during breaks did not occur with HFNT. Compared to SO, HFNT did not reduce time on NIV. However, it was more comfortable and the increase in RR and dyspnea seen with SO did not occur with HFNT. Therefore, HFNT could be a suitable alternative to SO during breaks off NIV. •Pilot randomized trial assessing the role of HFNT as complementary therapy to NIV.•HFNT does not affect the time on and off NIV compared to SO.•HFNT is well tolerated and leads to greater comfort than SO.•HFNT prevents increase in RR and dyspnea observed with SO during breaks off NIV.•HFNT could be a suitable alternative to SO during breaks off NIV.

Objective Exposure to hyperoxemia and hypoxemia is common in out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation (ROSC), but its effects on neurological outcome are uncertain, and study results are inconsistent. Methods Exploratory post hoc substudy of the Target Temperature Management (TTM) trial, including 939 patients after OHCA with return of spontaneous circulation (ROSC). The association between serial arterial partial pressures of oxygen (PaO 2 ) during 37 h following ROSC and neurological outcome at 6 months, evaluated by Cerebral Performance Category (CPC), dichotomized to good (CPC 1–2) and poor (CPC 3–5), was investigated. In our analyses, we tested the association of hyperoxemia and hypoxemia, time-weighted mean PaO 2 , maximum PaO 2 difference, and gradually increasing PaO 2 levels (13.3–53.3 kPa) with poor neurological outcome. A subsequent analysis investigated the association between PaO 2 and a biomarker of brain injury, peak serum Tau levels. Results Eight hundred sixty-nine patients were eligible for analysis. Three hundred patients (35%) were exposed to hyperoxemia or hypoxemia at some time point after ROSC. Our analyses did not reveal a significant association between hyperoxemia, hypoxemia, time-weighted mean PaO 2 exposure or maximum PaO 2 difference and poor neurological outcome at 6-month follow-up after correction for co-variates (all analyses p  = 0.146–0.847). We were not able to define a PaO 2 level significantly associated with the onset of poor neurological outcome. Peak serum Tau levels at either 48 or 72 h after ROSC were not associated with PaO 2 . Conclusion Hyperoxemia or hypoxemia exposure occurred in one third of the patients during the first 37 h of hospitalization and was not significantly associated with poor neurological outcome after 6 months or with the peak s-Tau levels at either 48 or 72 h after ROSC.

Background and Objectives: Percutaneous liver radiofrequency ablation (RFA) under monitored anesthesia care (MAC) carries a risk of hypoxia due to respiratory depression. Ensuring adequate oxygenation during such procedures is essential for patient safety. This study aimed to evaluate whether a high-flow nasal cannula (HFNC) improves oxygenation compared to a simple facemask during RFA. Materials and Methods: In this prospective, randomized controlled trial, 51 patients undergoing ultrasound-guided RFA under MAC were allocated to receive oxygen via an HFNC (30 L/min) or a facemask (6 L/min). Arterial blood gases were collected at the baseline and 5 min after oxygenation. The primary outcome was the arterial partial pressure of oxygen (PaO2). Secondary outcomes included hypoxia incidence (SpO2 < 95%), the difference in the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen concentration (ΔP/F ratio), the difference in the arterial partial pressure of carbon dioxide (ΔPaCO2), respiratory rate (RR) changes, and patient satisfaction. Results: After adjustment for the baseline PaO2, the HFNC group showed significantly higher intra-procedural PaO2 compared to the facemask group (299 ± 18.6 vs. 194 ± 19.0 mmHg, p < 0.001). No significant differences were found in the ΔP/F ratio, ΔPaCO2, or patient satisfaction. Among the secondary outcomes, RR was more stable in the HFNC group throughout the procedure (Group × Time interaction, p = 0.003). Conclusions: The HFNC significantly improved intra-procedural PaO2 during RFA under MAC but did not reduce hypoxia incidence or improve other clinical outcomes compared to facemask oxygenation. The stability of RR observed with the HFNC may reflect a physiological advantage, though further studies are needed to determine its clinical relevance.

BackgroundObstructive sleep apnoea (OSA) is highly prevalent and associated with cardiovascular and metabolic changes. OSA is usually diagnosed by polysomnography which is time-consuming and provides little information on the patient's phenotype thus limiting a personalised treatment approach. Exhaled breath contains information on metabolism which can be analysed by mass spectrometry within minutes. The objective of this study was to identify a breath profile in OSA recurrence by use of secondary-electrospray-ionization-mass spectrometry (SESI-MS).MethodsPatients with OSA effectively treated with CPAP were randomised to either withdraw treatment (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Exhaled breath analysis by untargeted SESI-MS was performed at baseline and 2 weeks after randomisation. The primary outcome was the change in exhaled molecular breath pattern.Results30 patients with OSA were randomised and 26 completed the trial according to the protocol. CPAP withdrawal led to a recurrence of OSA (mean difference in change of oxygen desaturation index between groups +30.3/h; 95% CI 19.8/h,40.7/h, p<0.001) which was accompanied by a significant change in 62 exhaled features (16 metabolites identified). The panel of discriminating mass-spectral features allowed differentiation between treated and untreated OSA with a sensitivity of 92.9% and a specificity of 84.6%.ConclusionExhaled breath analysis by SESI-MS allows rapid and accurate detection of OSA recurrence. The technique has the potential to characterise an individual's metabolic response to OSA and thus makes a comprehensible phenotyping of OSA possible.Trial registration numberNCT02050425 (registered at ClinicalTrials.gov).

The 18O/16O of calcite fossils increased by ∼8‰ between the Cambrian and present. It has long been controversial whether this change reflects evolution in the δ18O of seawater, or a decrease in ocean temperatures, or greater extents of diagenesis of older strata. Here, we present measurements of the oxygen and “clumped” isotope compositions of Phanerozoic dolomites and compare these data with published oxygen isotope studies of carbonate rocks. We show that the δ18O values of dolomites and calcite fossils of similar age overlap one another, suggesting they are controlled by similar processes. Clumped isotope measurements of Cambrian to Pleistocene dolomites imply crystallization temperatures of 15–158 °C and parent waters having δ18OVSMOW values from −2 to +12‰. These data are consistent with dolomitization through sediment/ rock reaction with seawater and diagenetically modified seawater, over timescales of 100 My, and suggest that, like dolomite, temporal variations of the calcite fossil δ18O record are largely driven by diagenetic alteration. We find no evidence that Phanerozoic seawater was significantly lower in δ18O than preglacial Cenozoic seawater. Thus, the fluxes of oxygen–isotope exchange associated with weathering and hydrothermal alteration reactions have remained stable throughout the Phanerozoic, despite major tectonic, climatic and biologic perturbations. This stability implies that a long-term feedback exists between the global rates of seafloor spreading and weathering. We note that massive dolomites have crystallized in pre-Cenozoic units at temperatures >40 °C. Since Cenozoic platforms generally have not reached such conditions, their thermal immaturity could explain their paucity of dolomites.

Background Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO 2 ) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients. Methods We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO 2 in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO 2 and serum NSE concentrations and the association between rSO 2 and good (CPC 1–2) and poor (CPC 3–5) neurological outcome. Results The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4–25.0) μg/l in patients with good neurological outcome and 35.2 (22.6–95.8) μg/l in those with poor outcome, p  < 0.001. We found no significant correlation between median rSO 2 and NSE at 48 h, r s  = − 0.08, p  = 0.392. The median (IQR) rSO 2 during the first 36 h of intensive care was 70.0% (63.5–77.0%) in patients with good outcome and 71.8% (63.3–74.0%) in patients with poor outcome, p  = 0.943. There was no significant association between rSO 2 over time and neurological outcome. In a binary logistic regression model, rSO 2 was not a statistically significant predictor of good neurological outcome (odds ratio 0.99, 95% confidence interval 0.94–1.04, p  = 0.635). Conclusions We found no association between cerebral oxygenation measured with NIRS and NSE concentrations or outcome in patients resuscitated from OHCA. Trial registration ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.

To analyse i) the association of physical fitness during early second trimester and late pregnancy with maternal and neonatal outcomes; and ii) to investigate whether physical fitness is associated with the type of birth (vaginal or caesarean section). Pregnant women from the GESTAFIT Project (n = 159) participated in this longitudinal study. Maternal physical fitness including upper- and lower-body strength, cardiorespiratory fitness (CRF) and flexibility were measured through objective physical fitness tests at the 16th and 34th gestational weeks. Maternal and neonatal outcomes were collected from obstetric medical records. Umbilical arterial and venous blood gas pH and partial pressure of carbon dioxide (PCO2) and oxygen (PO2), were assessed. At the 16th week, greater upper-body muscle strength was associated with greater neonatal birth weight (r = 0.191, p<0.05). Maternal flexibility was associated with a more alkaline arterial pH (r = 0.220, p<0.05), higher arterial PO2 (r = 0.237, p<0.05) and lower arterial PCO2 (r = -0.331, p<0.01) in umbilical cord blood. Maternal CRF at the 16th gestational week was related to higher arterial umbilical cord PO2 (r = 0.267, p<0.05). The women who had caesarean sections had lower CRF (p<0.001) at the 16th gestational week and worse clustered overall physical fitness, both at the 16th (-0.227, p = 0.003, confidence interval (CI): -0.376, -0.078) and 34th gestational week (-0.223; p = 0.018; CI: -0.432, -0.015) compared with the women who had vaginal births. Increasing physical fitness during pregnancy may promote better neonatal outcomes and is associated with a decrease in the risk of caesarean section. This trial was registered at ClinicalTrials.gov (NCT02582567) on October 20, 2015.