Key Physiological Variables Research Articles

Baseline Characteristics and ICS/LAMA/LABA Response in Asthma: Analyses From the CAPTAIN Study

BackgroundFindings from CAPTAIN (NCT02924688) suggest treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2 (T2) inflammation markers in patients with moderate-to-severe asthma. Understanding how other patient physiologic and clinical characteristics affect response to inhaled therapies may guide physicians toward a personalized approach for asthma management. ObjectiveTo investigate, using CAPTAIN data, the predictive value of key demographic and baseline physiologic variables in patients with asthma (lung function, bronchodilator reversibility, age, age at asthma onset) on response to addition of the long-acting muscarinic antagonist UMEC to inhaled corticosteroid/long-acting β2-agonist combination FF/VI, or doubling FF dose. MethodsPrespecified and post hoc analyses of CAPTAIN data were performed using categorical and continuous variables of key baseline characteristics to understand their influence on treatment outcomes (lung function [trough forced expiratory volume in 1 second, FEV1], annualized rate of moderate/severe exacerbations, and asthma control [Asthma Control Questionnaire, ACQ]) following addition of UMEC to FF/VI or doubling FF dose in FF/VI or FF/UMEC/VI. ResultsAdding UMEC to FF/VI led to greater improvements in trough FEV1 versus doubling FF dose across all baseline characteristics assessed. Doubling FF dose was generally associated with numerically greater reductions in the annualized rate of moderate/severe exacerbations compared with adding UMEC, independent of baseline characteristics. Adding UMEC and/or doubling FF dose generally led to improvements in ACQ scores irrespective of baseline characteristics. ConclusionUnlike previous findings with T2 biomarkers, lung function, bronchodilator reversibility, age and age at asthma onset do not appear to predict response to inhaled therapy.

CO2 Stunning in Pigs: Physiological Deviations at Onset of Excitatory Behaviour.

Stunning by carbon dioxide (CO2) inhalation is controversial because it is associated with vigorous movements and behaviours which may or may not be conscious reactions. Furthermore, it is unknown whether some behaviours might indicate the transition into unconsciousness. Our study objective was to investigate the loss of consciousness during CO2 stunning by linking physiological variables (in particular pH, PaO2 and PaCO2) to the onset of observed behaviours. A total of 11 cross-bred pigs were studied. A tracheostomy tube, venous and arterial cannulae were placed under sevoflurane anaesthesia. After recovery from this, and a "wash out" period of at least 30 min, arterial blood samples were taken (and baseline values established) before 90-95% CO2 in medical air was administered through the tracheostomy tube. Subsequent behaviours were video-recorded and key physiological variables were evaluated using an anaesthetic monitor and the frequent sampling of arterial blood (albeit with inconsistent inter-sample intervals). After the study, behaviours were classified in an ethogram. At the onset of behaviours categorised as "vigorous movement extremities", "opisthotonos" and "agonal gasping" pH values (range) were: 6.74-7.34; 6.66-6.96 and 6.65-6.87, while PaCO2 (kPa) was 4.6-42.2, 24.4-51.4 and 29.1-47.6. Based upon these values, we conclude that the pigs were probably unconscious at the onset of "opisthotonos" and "agonal gasping", but some were probably conscious at the onset of "vigorous movements".

Comparison of Different Important Predictors and Models for Estimating Large-Scale Biomass of Rubber Plantations in Hainan Island, China

Rubber (Hevea brasiliensis Muell.) plantations are among the most critical agricultural ecosystems in tropical regions, playing a vital role in regional carbon balance. Accurate large-scale biomass estimation for these plantations remains a challenging task due to the severe signal saturation problem. Recent advances in remote sensing big data, cloud platforms, and machine learning have facilitated the precise acquisition of key physiological variables, such as stand age (A) and canopy height (H), which are critical parameters for biomass estimation but have been underutilized in prior studies. Using Hainan Island—the second-largest rubber planting base in China—as a case study, we integrated extensive ground surveys, maps of stand age and canopy height, remote sensing indicators (RSIs), and geographical and climate indicators (ECIs) to ascertain the optimal method for estimating rubber plantation biomass. We compared different inputs and estimation approaches (direct and indirect) using the random forest algorithm and analyzed the spatiotemporal characteristics of rubber plantation biomass on Hainan Island. The results indicated that the traditional model (RSIs + ECIs) had low accuracy and significant estimation bias (R2 = 0.24, RMSE = 38.36 mg/ha). The addition of either stand age or canopy height considerably enhance model accuracy (R2 = 0.77, RMSE ≈ 21.12 mg/ha). Moreover, incorporating the DBH obtained through indirect inversion yielded even greater predictive accuracy (R2 = 0.97, RMSE = 7.73 mg/ha), outperforming estimates derived from an allometric equation model input with the DBH (R2 = 0.67, RMSE = 25.43 mg/ha). However, augmenting the model with stand age, canopy height, or their combination based on RSIs, ECIs, and DBH only marginally improved the accuracy. Consequently, it is not recommended in scenarios with limited data and computing resources. Employing the optimal model, we generated biomass maps of rubber plantations on Hainan Island for 2016 and 2020, revealing that the spatiotemporal distribution pattern of the biomass is closely associated with the establishment year of the rubber plantations. While average biomass in a few areas has undergone slight decreases, total biomass has exhibited significant growth, reaching 5.46 × 107 mg by the end of 2020, underscoring its considerable value as a carbon sink.

Physiological Variables Influenced by 'Candidatus Liberibacter asiaticus' Infection in Two Citrus Species.

'Candidatus Liberibacter asiaticus' is the bacterium associated with the citrus disease known as huanglongbing (HLB). This study evaluated the influence of 'Ca. L. asiaticus' infection on a number of key plant physiological variables concerning photosynthesis, cell integrity, reactive oxygen species scavengers' activity, and osmoregulation of two different species of citrus-the pomelo Citrus maxima and the mandarin C. reticulata 'Tankan'-relative to their measured 'Ca. L. asiaticus' infection load. Results indicated that all measured physiological variables except soluble sugar were affected by increased 'Ca. L. asiaticus' infection titers, wherein the variety C. maxima proved overall more resistant than C. reticulata. 'Ca. L. asiaticus' infection was linked in both plants to decrease in chlorophyll concentration, cell membrane permeability, and malondialdehyde, as well as increased free proline and starch contents. Chlorophyll fluorescence measurements taken 9 months after grafting the mandarin C. reticulata with 'Ca. L. asiaticus' scions revealed a significant decrease in the photosynthesis variables maximum photochemical quantum yield of photosystem II (PSII), effective photochemical quantum yield of PSII, and coefficient of photochemical fluorescence quenching assuming interconnected PSII antennae, whereas nonphotochemical fluorescence quenching increased significantly; C. maxima plants, on the other hand, did not show significant differences until the 12th month from infection exposure. The variables superoxide dismutase, catalase, peroxidase, and soluble protein initially increased and later decreased. In addition, progression of 'Ca. L. asiaticus' replication in both citrus species was accompanied by rapid changes in three reactive oxygen species scavenging enzymes in C. maxima, while the pattern was different in C. reticulata. We hypothesize that the observed interspecific differences in physiological change are related to their relative resistance against 'Ca. L. asiaticus' infection. These results provide a scaffold for better describing the pathogenesis, selecting the most resistant breeds, or even validating pertaining omics research; ultimately, these detailed observations can facilitate the diagnosis of 'Ca. L. asiaticus' infection.

Universal structural requirements for maximal robust perfect adaptation in biomolecular networks

Adaptation is a running theme in biology. It allows a living system to survive and thrive in the face of unpredictable environments by maintaining key physiological variables at their desired levels through tight regulation. When one such variable is maintained at a certain value at the steady state despite perturbations to a single input, this property is called robust perfect adaptation (RPA). Here we address and solve the fundamental problem of maximal RPA (maxRPA), whereby, for a designated output variable, RPA is achieved with respect to perturbations in virtually all network parameters. In particular, we show that the maxRPA property imposes certain structural constraints on the network. We then prove that these constraints are fully characterized by simple linear algebraic stoichiometric conditions which differ between deterministic and stochastic descriptions of the dynamics. We use our results to derive a new internal model principle (IMP) for biomolecular maxRPA networks, akin to the celebrated IMP in control theory. We exemplify our results through several known biological examples of robustly adapting networks and construct examples of such networks with the aid of our linear algebraic characterization. Our results reveal the universal requirements for maxRPA in all biological systems, and establish a foundation for studying adaptation in general biomolecular networks, with important implications for both systems and synthetic biology.

Carbon Isotope Fractionation in Noelaerhabdaceae Algae in Culture and a Critical Evaluation of the Alkenone Paleobarometer

AbstractThe carbon isotope fractionation in algal organic matter (εp), including the long‐chain alkenones produced by the coccolithophorid family Noelaerhabdaceae, is used to reconstruct past atmospheric CO2 levels. The conventional proxy linearly relates εp to changes in cellular carbon demand relative to diffusive CO2 supply, with larger εp values occurring at lower carbon demand relative to supply (i.e., abundant CO2). However, the response of Gephyrocapsa oceanica, one of the dominant alkenone producers of the last few million years, has not been studied closely. Here, we subject G. oceanica to various CO2 levels by increasing pCO2 in the culture headspace, as opposed to increasing dissolved inorganic carbon (DIC) and alkalinity concentrations at constant pH. We note no substantial change in physiology, but observe an increase in εp as carbon demand relative to supply decreases, consistent with DIC manipulations. We compile existing Noelaerhabdaceae εp data and show that the diffusive model poorly describes the data. A meta‐analysis of individual treatments (unique combinations of lab, strain, and light conditions) shows that the slope of the εp response depends on the light conditions and range of carbon demand relative to CO2 supply in the treatment, which is incompatible with the diffusive model. We model εp as a multilinear function of key physiological and environmental variables and find that both photoperiod duration and light intensity are critical parameters, in addition to CO2 and cell size. While alkenone carbon isotope ratios indeed record CO2 information, irradiance and other factors are also necessary to properly describe alkenone εp.

Concordance of expert clinicians' interpretations of the newborn's true physiological state.

BackgroundMany physiological aspects of the neonatal transition after birth are unobservable because relevant sensors do not yet exist, compromising clinicians’ understanding of a neonate’s physiological status. Given that a neonate’s true physiological state is currently unavailable, we explored the feasibility of using clinicians’ degree of concordance as an approximation of the true physiological state.MethodsTwo phases of structured interviews were conducted. In Phase 1 (N = 8) and Phase 2 (N = 12), we presented neonatal experts with eight graphical trajectories of real newborns’ heart rate and oxygen saturation values in the first 10–15 min after birth. We elicited the participants’ interpretations of potential underlying physiological conditions that could explain the vital sign patterns.ResultsThe global differential diagnosis data for each phase produced the same pattern of results: (1) four trajectories produced a substantial degree of concordance among clinicians (61–80%) and (2) four trajectories produced a strong degree of concordance among clinicians (81–100%).ConclusionsIt is possible to achieve a strong degree of concordance among neonatal experts’ interpretations of newborn trajectories. Thus, using the degree of concordance as an approximation of the neonate’s true physiological state in resuscitation after birth may be a promising direction to explore for cognitive aid design.Impact Differential diagnoses with a good degree of concordance among expert neonatal clinicians could potentially substitute in part for the direct measurement of key physiological and anatomical variables of the neonatal transition, which is currently unavailable.The concordance of clinicians’ judgements or inferences with regards to the true physiological state of the newborn during resuscitation after birth has never been explored.The findings provide a crucial first step toward using consensus of neonatal experts’ judgements in the design of a cognitive aid to support clinicians’ management of the newborns who require resuscitation after birth.

Abstract MP34: Retrospective Analysis on Predictive Factors and Timeline for Early Neurologic Decline and Symptomatic Intracranial Hemorrhage Following Administration of Intravenous Recombinant Tissue Plasminogen Activator for Ischemic Stroke

Introduction: Current guidelines recommend that patients given intravenous tPA (IV tPA) for acute ischemic stroke (AIS) receive comprehensive stroke care for 24 hours post-treatment to monitor key physiologic variables. 1,2,3 Early de-escalation of monitoring is likely feasible in a particular subset of patients, which may have implications in the post-COVID era. 4 In this study, we examined when patients with AIS are susceptible to early neurologic decline (END) and symptomatic intracranial hemorrhage (sICH) after IV tPA and whether those at low clinical risk of neurologic deterioration may be suitable for earlier transition to lower level of care. Methods: We performed a retrospective analysis of AIS receiving IV tPA based on AHA/ASA guidelines. We included those that presented within 4.5 hours of last seen well (LSW) without large vessel occlusion (LVO) or flow-limiting stenosis (FLS) on non-invasive angiographic imaging. Outcomes included END (≥4-point worsening of NIHSS at 24 hours) from any cause, parenchymal hemorrhage (PH1 or PH2), and/ or symptomatic intracranial hemorrhage (sICH; ≥4-point NIHSS worsening with presence of hemorrhage). Results: 1238 patients were included from 1/2013 - 6/2019. END and ICH occurred in 7.4% (91) and 9.4% (116), respectively. 63.7% of patients with END did not have ICH within 24 hours. In those with NIHSS <12, 82% had END within 12 hours and most occurred within 5 hours. Predictive factors included older patients (72.6 ±16.1 vs 69.1 ±14.8, p=0.03), history of tobacco use (OR-2.1 [1.1-4.3], p = 0.04) and hyperlipidemia (OR-1.7 [1.1-2.8] p = 0.02). ICH occurred within 12 hours in 30% of patients, predictors included older age (74.6 ± 12.4 vs 68.8 ± 15.1, p ≤ 0.01), higher NIHSS (14.6 ± 7.3 vs 10.8 ± 7.9, p ≤ 0.01), and higher presentation serum glucose levels (155.1 ± 87.5 vs 140.4 ± 70.5, p = 0.04). Overall, only 2.7% (33) of patients developed sICH. There were no independent predictive factors for delayed ICH (≥ 12 hours). Conclusion: In our selected post-IV tPA patients, a relatively small proportion suffered sICH and END; most often within 12 hours of tPA administration. These findings may support earlier de-escalation of higher acuity monitoring for clinically stable post-IV tPA patients.

Matchmaking and the Future of Hypertension Management.

Matchmaking and the Future of Hypertension Management.

Mercury Exposure and Toxicological Consequences in Fish and Fish-Eating Wildlife from Anthropogenic Activity in Latin America.

ABSTRACTDespite the risk of significant adverse toxicological effects of Hg to humans and wildlife, Hg use in anthropogenic activities, and artisanal small‐scale gold mining (ASGM) in particular, is widespread throughout Latin America. However, there are few research and monitoring studies of Hg toxicity in fish and fish‐eating wildlife in Latin America compared to North America. In the present paper, we reviewed the literature from published articles and reports and summarized and assessed data on Hg in fish from 10 391 individuals and 192 species sampled across Latin America. We compared fish Hg levels with toxicity reference values (TRVs) for fish and dietary TRVs for fish‐eating wildlife. We determined that fish, piscivorous birds, and other wildlife are at risk of Hg toxicity. We observed a large disparity in data quantity between North and Latin America, and identified regions requiring further investigation. In particular, future biomonitoring and research should focus on exposure of wildlife to Hg in Peru, Chile, Uruguay, the eastern and northern regions of Brazil, Venezuela, Ecuador, and Colombia. We also discuss Hg risk assessment methodological issues and recommend that future evaluations of Hg risk to wildlife must collect key physiological variables, including age, body size, and ideally Hg‐to‐Se molar ratios. Integr Environ Assess Manag 2021;17:13–26. © 2020 Environment and Climate Change Canada. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Clinical effectiveness of a silicone foam dressing for the prevention of heel pressure ulcers in critically ill patients: Border II Trial

Critically ill patients are at high risk of developing pressure ulcers (PU), with the sacrum and heels being highly susceptible to pressure injuries. The objective of our study was to evaluate the clinical effectiveness of a new multi-layer, self-adhesive soft silicone foam heel dressing to prevent PU development in trauma and critically ill patients in the intensive care unit (ICU). A cohort of critically ill patients were enrolled at the Royal Melbourne Hospital. Each patient had the multi-layer soft silicone foam dressing applied to each heel on admission to the emergency department. The dressings were retained with a tubular bandage for the duration of the patients' stay in the ICU. The skin under the dressings was examined daily and the dressings were replaced every three days. The comparator for our cohort study was the control group from the recently completed Border Trial. Of the 191 patients in the initial cohort, excluding deaths, loss to follow-up and transfers to another ward, 150 patients were included in the final analysis. There was no difference in key demographic or physiological variables between the cohorts, apart from a longer ICU length of stay for our current cohort. No PUs developed in any of our intervention cohort patients compared with 14 patients in the control cohort (n=152; p<0.001) who developed a total of 19 heel PUs. We conclude, based on our results, that the multi-layer soft silicone foam dressing under investigation was clinically effective in reducing ICU-acquired heel PUs. The findings also support previous research on the clinical effectiveness of multi-layer soft silicone foam dressings for PU prevention in the ICU.

Successful use of an artificial placenta–based life support system to treat extremely preterm ovine fetuses compromised by intrauterine inflammation

Exvivo uterine environment therapy is an experimental intensive care strategy for extremely preterm infants born between 21 and 24 weeks of gestation. Gas exchange is performed by membranous oxygenators connected by catheters to the umbilical vessels. The fetus is submerged in a bath of synthetic amniotic fluid. The lungs remain fluid filled, and pulmonary respiration does not occur. Intrauterine inflammation is strongly associated with extremely preterm birth and fetal injury. At present, there are no data that we are aware of to show that artificial placenta-based systems can be used to support extremely preterm fetuses compromised by exposure to intrauterine inflammation. To evaluate the ability of our exvivo uterine environment therapy platform to support extremely preterm ovine fetuses (95-day gestational age; approximately equivalent to 24 weeks of human gestation) exposed to intrauterine inflammation for a period of 120 hours, the following primary endpoints were chosen: (1) maintenance of key physiological variables within normal ranges, (2) absence of infection and inflammation, (3) absence of brain injury, and (4) gross fetal growth and cardiovascular function matching that of age-matched in utero controls. Ten ewes with singleton pregnancies were each given a single intraamniotic injection of 10-mg Escherichia coli lipopolysaccharides under ultrasound guidance 48 hours before undergoing surgical delivery for adaptation to exvivo uterine environment therapy at 95-day gestation (term=150 days). Fetuses were adapted to exvivo uterine environment therapy and maintained for 120 hours with constant monitoring of key vital parameters (exvivo uterine environment group) before being killed at 100-day equivalent gestational age. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, biochemical parameters, inflammatory markers, and microbial load to exclude infection. Ultrasound was conducted at 48 hours after intraamniotic lipopolysaccharides (before surgery) to confirm fetal viability and at the conclusion of the experiments (before euthanasia) to evaluate cardiac function. Brain injury was evaluated by gross anatomic and histopathologic investigations. Eight singleton pregnant control animals were similarly exposed to intraamniotic lipopolysaccharides at 93-day gestation and were killed at 100-day gestation to allow comparative postmortem analyses (control group). Biobanked samples from age-matched saline-treated animals served as an additional comparison group. Successful instillation of lipopolysaccharides into the amniotic fluid exposure was confirmed by amniotic fluid analysis at the time of administration and by analyzing cytokine levels in fetal plasma and amniotic fluid. Data were tested for mean differences using analysis of variance. Six of 8 lipopolysaccharide control group (75%) and 8 of 10 exvivo uterine environment group fetuses (80%) successfully completed their protocols. Six of 8 exvivo uterine environment group fetuses required dexamethasone phosphate treatment to manage profound refractory hypotension. Weight and crown-rump length were reduced in exvivo uterine environment group fetuses at euthanasia than those in lipopolysaccharide control group fetuses (P<.05). There were no biologically significant differences in cardiac ultrasound measurement, differential leukocyte counts (P>.05), plasma tumor necrosis factor α, monocyte chemoattractant protein-1 concentrations (P>.05), or liver function tests between groups. Daily blood cultures were negative for aerobic and anaerobic growth in all exvivo uterine environment group animals. No cases of intraventricular hemorrhage were observed. White matter injury was identified in 3 of 6 lipopolysaccharide control group fetuses and 3 of 8 vivo uterine environment group fetuses. We report the use of an artificial placenta-based system to support extremely preterm lambs compromised by exposure to intrauterine inflammation. Our data highlight key challenges (refractory hypotension, growth restriction, and white matter injury) to be overcome in the development and use of artificial placenta technology for extremely preterm infants. As such challenges seem largely absent from studies based on healthy pregnancies, additional experiments of this nature using clinically relevant model systems are essential for further development of this technology and its eventual clinical application.

Critical speed and finite distance capacity: norms for athletic and non-athletic groups.

Two parameters in particular span both health and performance; critical speed (CS) and finite distance capacity (D'). The purpose of the present study was to: (1) classify performance norms, (2) distinguish athletic from non-athletic individuals using the 3-min all-out test (3MT) for running, and (3) introduce a deterministic model highlighting the relationship between variables of the 3MT. Athletic (n = 43) and non-athletic (n = 25) individuals participated in the study. All participants completed a treadmill graded exercise test (GXT) with verification bout and a 3MT on an outdoor sprinting track. Meaningful differences between non-athletic and athletic individuals (denoted by mean difference scores, p value and Cohen's d with 95% confidence intervals) were evident for CS (- 0.74ms-1, p < 0.001, d = - 1.41 [1.97, - 0.87]), exponential growth time constant ([Formula: see text]; 2.75s, p < 0.001, d = - 1.29 [- 1.45, - 0.42]), time to maximal speed ([Formula: see text]; - 2.80s, p < 0.001, d = - 0.98 [- 1.51, - 0.47]), maximal speed ([Formula: see text]; - 1.36ms-1, p < 0.001, d = - 1.56 [- 2.13, - 1.01]), gas exchange threshold (GET; - 5.62mlkg-1min-1, p < 0.001, d = - 0.97 [- 1.50, - 0.45]), distance covered in the first minute (1st min; - 81.69m, p < 0.001, d = - 1.91 [- 2.52, - 1.33]), distance covered in the second minute (2nd min; - 52.02m, p < 0.001, d = - 1.71 [- 2.30, - 1.15]) and maximal distance (- 153.78m, p < 0.001, d = - 1.27 [- 1.82, - 0.74]). The correlation coefficient between key physiological and performance variables are shown in the form of a deterministic model created from the data derived from the 3MT. Coaches and clinicians may benefit from the use of normative data to potentially identify exceptional or irregular occurrences in 3MT performances.

The role of ambient temperature and body mass on body temperature, standard metabolic rate and evaporative water loss in southern African anurans of different habitat specialisation.

Temperature and water availability are two of the most important variables affecting all aspects of an anuran’s key physiological processes such as body temperature (Tb), evaporative water loss (EWL) and standard metabolic rate (SMR). Since anurans display pronounced sexual dimorphism, evidence suggests that these processes are further influenced by other factors such as vapour pressure deficit (VPD), sex and body mass (Mb). However, a limited number of studies have tested the generality of these results across a wide range of ecologically relevant ambient temperatures (Ta), while taking habitat use into account. Thus, the aim of this study was to investigate the role of Ta on Tb, whole-animal EWL and whole-animal SMR in three wild caught African anuran species with different ecological specialisations: the principally aquatic African clawed frog (Xenopus laevis), stream-breeding common river frog (Amietia delalandii), and the largely terrestrial raucous toad (Sclerophrys capensis). Experiments were conducted at a range of test temperatures (5–35 °C, at 5 °C increments). We found that VPD better predicted rates of EWL than Ta in two of the three species considered. Moreover, we found that Tb, whole-animal EWL and whole-animal SMR increased with increasing Ta, while Tb increased with increasing Mb in A. delalandii and S. capensis but not in X. laevis. Whole-animal SMR increased with increasing Mb in S. capensis only. We did not find any significant effect of VPD, Mb or sex on whole-animal EWL within species. Lastly, Mb did not influence Tb, whole-animal SMR and EWL in the principally aquatic X. laevis. These results suggest that Mb may not have the same effect on key physiological variables, and that the influence of Mb may also depend on the species ecological specialisation. Thus, the generality of Mb as an important factor should be taken in the context of both physiology and species habitat specialisation.

Climatic and physiological regulation of the bimodal xylem formation pattern in Pinus pinaster saplings.

Seasonality in tree cambial activity and xylem formation encompass large variation in environmental conditions. Abiotic stressors such as warming or drought also modulate plant behavior at species and individual level. Despite xylem formation susceptibility to carbon (C) and water availability, it is still unknown which are the key physiological variables that regulate xylogenesis, and to what extent plant performance contributes to further explain the number of cells in the different phases of xylem development. Xylogenesis and physiological behavior was monitored in saplings of Pinus pinaster Aiton, a bimodal growth pattern species, distributed in different irrigation regimes. Xylogenesis and plant physiological behavior were compared between treatments and the relationship between climate, physiology and the number of cells in the cambium, enlargement and cell-wall thickening phases was evaluated. Xylogenesis regulation shifted from physiological to climatic control as cell differentiation advanced to mature tracheids. The number of cells in the cambium increased with assimilation rates and decreased with the water potential gradient through the plant. Enlargement was the most susceptible phase to plant relative water content, whereas no physiological variable contributed to explain the number of cells in the wall thickening phase, which declined as temperatures increased. All treatments showed a bimodal growth pattern with a second growth period starting when primary growth was completed and after plants had experienced the highest summer hydraulic losses. Our study demonstrates the importance of including physiological responses and not only climate to fully understand xylogenesis, with special attention to the enlargement phase. This is critical when studying species with a bimodal growth pattern because the second growth peak responds to internal shifts of C allocation and may strongly depend on plant hydraulic responses and not on a fine tuning of cambial activity with soil water availability.

Successful use of an artificial placenta to support extremely preterm ovine fetuses at the border of viability

Exvivo uterine environment therapy is an experimental life support platform designed to reduce the risk of morbidity and mortality for extremely preterm infants born at the border of viability (21-24 weeks' gestation). To spare the functionally immature lung, this platform performs gas exchange via a membranous oxygenator connected to the umbilical vessels, and the fetus is submerged in a protective bath of artificial amniotic fluid. We and others have demonstrated the feasibility of extended survival with exvivo uterine environment therapy therapy in late preterm fetuses; however, there is presently no evidence to show that the use of such a platform can support extremely preterm fetuses, the eventual translational target for therapy of this nature. The objective of the study was to use our exvivo uterine environment therapy platform to support the healthy maintenance of 600-700 g/95 days gestational age (equivalent to 24 weeks of human gestation) sheep fetuses. Primary outcome measures were as follows: (1) maintenance of key physiological variables; (2) absence of infection; (3) absence of brain injury; and (4) growth and cardiovascular function patterns matching that of noninstrumented, age-matched in utero controls. Singleton fetuses from 8 ewes underwent surgical delivery at 95 days' gestation (term, 150 days). Fetuses were adapted to exvivo uterine environment therapy and maintained for 120 hours with real-time monitoring of key physiological variables. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, inflammation, and microbial load to exclude infection. Brain injury was evaluated by gross anatomical and histopathological approaches after euthanasia. Nine pregnant control animals were euthanized at 100 days' gestation to allow comparative postmortem analyses. Data were tested for mean differences with an analysis of variance. Seven of 8 exvivo uterine environment group fetuses (87.5%) completed 120 hours of therapy with key parameters maintained in a normal physiological range. There were no significant intergroup differences (P > .05) in final weight, crown-rump length, and body weight-normalized lung and brain weights at euthanasia compared with controls. There were no biologically significant differences in hematological parameters (total or differential leucocyte counts and plasma concentration of tumor necrosis factor-α and monocyte chemoattractant protein 1) (P > .05). Daily blood cultures were negative for aerobic and anaerobic growth in all exvivo uterine environment animals. There was no difference in airspace consolidation between control and exvivo uterine environment animals, and there was no increase in the number of lung cells staining positive for the T-cell marker CD3. There were no increases in interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-α, and monocyte chemoattractant protein 1 mRNA expression in lung tissues compared with the control group. No cases of intraventricular hemorrhage were observed, and white matter injury was identified in only 1 exvivo uterine environment fetus. For several decades, there has been little improvement in outcomes of extremely preterm infants born at the border of viability. In the present study, we report the use of artificial placenta technology to support, for the first time, extremely preterm ovine fetuses (equivalent to 24 weeks of human gestation) in a stable, growth-normal state for 120 hours. With additional refinement, the data generated by this study may inform a treatment option to improve outcomes for extremely preterm infants.

Apparent timing of density banding in the Caribbean coral Siderastrea siderea suggests complex role of key physiological variables

Apparent timing of density banding in the Caribbean coral Siderastrea siderea suggests complex role of key physiological variables

Pyramids and cascades: a synthesis of food chain functioning and stability.

Food chain theory is one of the cornerstones of ecology, providing many of its basic predictions, such as biomass pyramids, trophic cascades and predator-prey oscillations. Yet, ninety years into this theory, the conditions under which these patterns may occur and persist in nature remain subject to debate. Rather than address each pattern in isolation, we propose that they must be understood together, calling for synthesis in a fragmented landscape of theoretical and empirical results. As a first step, we propose a minimal theory that combines the long-standing energetic and dynamical approaches of food chains. We chart theoretical predictions on a concise map, where two main regimes emerge: across various functioning and stability metrics, one regime is characterised by pyramidal patterns and the other by cascade patterns. The axes of this map combine key physiological and ecological variables, such as metabolic rates and self-regulation. A quantitative comparison with data sheds light on conflicting theoretical predictions and empirical puzzles, from size spectra to causes of trophic cascade strength. We conclude that drawing systematic connections between various existing approaches to food chains, and between their predictions on functioning and stability, is a crucial step in confronting this theory to real ecosystems.

Apparent timing of density banding in the Caribbean coral Siderastrea siderea suggests complex role of key physiological variables

Skeletal growth bands in massive reef-building corals are increasingly used as proxies for environmental records despite an incomplete understanding of their formation. While the bands are known to arise from seasonal changes in light and temperature, conflicting reports about the timing of constituent high- and low-density growth bands have complicated the dating and interpretation of environmental signals recorded in corals’ growth histories. Here, we analyze 35 Siderastrea siderea cores extracted from inshore and offshore reef zones along the Florida Keys Reef Tract to investigate potential drivers of banding variability in this species. A previously proposed model of banding variation is applied to assess its potential to explain band timing in S. siderea. Colony growth characteristics and the timing of band deposition were obtained from the cores via computed tomography and were coupled with tissue thickness measurements and gender identification. Apparent time difference, or the perceived lag in coral growth response to changes in environmental conditions, was quantified for each coral core. Results suggest that linear extension, tissue thickness, and gender together do not fully explain the timing of band formation in S. siderea and therefore do not fully resolve the density patterns observed within this species. This finding suggests that other factors yet to be identified are partially determining the formation and appearance of density bands in S. siderea. The continued characterization of banding variability on scales ranging from the individual colony to entire reef systems will enrich our understanding of both coral growth and the environmental conditions to which corals are exposed.

Mortality prediction for ICU patients combining just-in-time learning and extreme learning machine

Abstract Mortality prediction for patients in intensive care unit (ICU) is necessary to prioritize resources as well as to help the medical staff to make decisions, and hence more accurate methods for identifying high risk patients are very important for improving clinical care. However, many existing approaches including some scoring systems now being used in the hospital are not good enough since they try to establish a global/average offline model, which may be unsuitable for a specific patient. Thus, a more robust and effective monitoring model adaptable to individual patients is needed. To establish a more personalized model, this study proposes a two-step framework, in which the first step is for clustering and while the second one is for mortality predication. A novel method combining just-in-time learning (JITL) and extreme learning machine (ELM), referred to JITL-ELM, is proposed for mortality prediction, which applies global optimization of variables and neighborhood of appropriate samples to build an accurate patient-specific model. In addition, a simplified JITL-ELM with less key physiological variables is developed. In the experiment, 4000 real clinical records of ICU patients are collected to validate the proposed algorithm, of which the AUC index is 0.8568, which is much better than the existing traditional global/average models, and furthermore the simplified JITL-ELM still performs well.