Land surface model parameter optimisation using in situ flux data: comparison of gradient-based versus random search algorithms (a case study using ORCHIDEE v1.9.5.2)

Land surface models (LSMs), which form the land component of earth system models, rely on numerous processes for describing carbon, water and energy budgets, often associated with highly uncertain parameters. Data assimilation (DA) is a useful approach for optimising the most critical parameters in order to improve model accuracy and refine future climate predictions. In this study, we compare two different DA methods for optimising the parameters of seven plant functional types (PFTs) of the ORCHIDEE LSM using daily averaged eddy-covariance observations of net ecosystem exchange and latent heat flux at 78 sites across the globe. We perform a technical investigation of two classes of minimisation methods – local gradient-based (the L-BFGS-B algorithm, limited memory Broyden–Fletcher–Goldfarb–Shanno algorithm with bound constraints) and global random search (the genetic algorithm) – by evaluating their relative performance in terms of the model–data fit and the difference in retrieved parameter values. We examine the performance of each method for two cases: when optimising parameters at each site independently (“single-site” approach) and when simultaneously optimising the model at all sites for a given PFT using a common set of parameters (“multi-site” approach). We find that for the single site case the random search algorithm results in lower values of the cost function (i.e. lower model–data root mean square differences) than the gradient-based method; the difference between the two methods is smaller for the multi-site optimisation due to a smoothing of the cost function shape with a greater number of observations. The spread of the cost function, when performing the same tests with 16 random first-guess parameters, is much larger with the gradient-based method, due to the higher likelihood of being trapped in local minima. When using pseudo-observation tests, the genetic algorithm results in a closer approximation of the true posterior parameter value in the L-BFGS-B algorithm. We demonstrate the advantages and challenges of different DA techniques and provide some advice on using it for the LSM parameter optimisation.</p

Influence of asthma and obesity on respiratory load perception in children

...Introduction: Elevated symptom burden has been reported in concomitant asthma and overweight, although objective evidence of greater disease severity is lacking. This may reflect exaggerated symptom perception and has implications for optimal asthma management. Aims: To investigate respiratory load perception in overweight asthmatic (OA) children compared to normal weight asthmatic children (NWA) and healthy controls (HC). Methods: Incremental inspiratory resistive loading was performed in 27 children (9 OA, 9 NWA, 9 HC) with load perception assessed by visual analogue scale (VAS). Respiratory load was quantified via parasternal intercostal electromyography (EMGpara) expressed as neuroventilatory efficiency (NVE: ratio of tidal volume to EMGpara (ml/μV)). Linear mixed model analysis was used to examine changes in perception scores and NVE with increasing resistance, and to determine the influence of asthma and overweight. Results: VAS increased significantly with increasing resistance (slope (95% CI) 5.06 (1.83 – 8.29)mm/kPa/L/s, p=0.002), which was additionally influenced by degree of reduction in NVE (p=0.004). The slopes of these relationships did not differ with group, indicating no effect of asthma or overweight on either perception or objective response to increasing load. Weight had a significant effect on the intercept of the VAS/resistance relationship, with OA having a significantly higher intercept (9.96mm (95% CI 1.15 – 18.77), p=0.027), suggesting breathlessness at rest and higher VAS scores throughout. Conclusions: Respiratory load perception is not influenced by weight status. The increased symptom burden in overweight asthmatics may be related to elevated baseline respiratory load.Meeting abstract presented at European Respiratory Society International Congress, London, UK, 3-7 September 2016

Dance as a rehabilitative strategy for patients with COPD

Copyright © the authors 2017. Pulmonary rehabilitation (PR) is a highly effective intervention for COPD, though lack of enjoyment and preconceptions about exercise impact on uptake, completion and maintenance of physical activity post-PR. We piloted dance classes led by an experienced choreographer and a trained dancer as an exercise modality for 5 patients with COPD (61–76 years, 3 female, GOLD 2-3). The intervention, comprising 1 hour of stretching, posture, balance, coordination and strength exercises based on a variety of movement and dance techniques and styles at low to high intensity, was trialled in 1 session and refined over 2 further sessions. During the latter 2 sessions heart rate (HR) was recorded; dyspnoea and leg fatigue numerical rating scale (NRS) values taken at 4 points during the class; participants rated mood, sense of group cohesion and enjoyment. Peak HR reached 79-95% of predicted maximum, and was maintained above 70%max for median 26% of class duration. Individual participants’ peak NRS values for dyspnoea ranged from 4–9, and for leg fatigue from 4–8. All participants showed improved mood (from median (range) 5 (4-7) to 7 (5-7)), sense of group cohesion (6 (3-6) to 7 (5-7)), deemed the sessions worthwhile (7 (6-7)), and expressed enjoyment (7 (6-7)) and a sense of achievement (6 (3-7)) on completion. Qualitative data indicated participants underestimated class duration by up to 15%, and that concentration on technique helped divert attention away from dyspnoea. Expert-led dance sessions may provide a suitable intensity of training stimulus to improve strength and fitness in individuals with COPD, with potential wider psychosocial benefits. A larger randomised trial is warranted to compare dance-based exercise to conventional PR

Participant retention in follow-up studies of prematurely born children

Background: Follow-up studies of infants born prematurely are essential to understand the long-term consequences of preterm birth and the efficacy of interventions delivered in the neonatal period. Retention of participants for follow up studies, however, is challenging, with attrition rates of up to 70%. Our aim was to examine retention rates in two follow-up studies of prematurely born children and identify participant or study characteristics that were associated with higher attrition, and to discuss retention strategies with regard to the literature. Methods: Data from children recruited at birth to one of two studies of prematurely born infants were assessed. The two studies were the United Kingdom Oscillation Study (UKOS, a randomised study comparing two modes of neonatal ventilation in infants born less than 29weeks of gestational age (GA)), and an observational study examining the impact of viral lower respiratory tract infections in infancy in those born less than 36weeks of GA (virus study). The UKOS participants, but not those in the virus study, had regularly been contacted throughout the follow-up period. UKOS subjects were followed up at 11 to 14years of age and subjects in the virus study at 5–7 years of age. At follow up in both studies, pulmonary function and respiratory morbidity were assessed. Retention rates to follow-up in the two studies and baseline characteristics of those who were and were not retained were assessed. Results: Retention was significantly higher in UKOS than the virus study (61% versus 35%, p <0.0001). Subjects lost to UKOS follow up had greater deprivation scores (p <0.001), a greater likelihood of intrauterine tobacco exposure (p =0.001) and were more likely to be of non-white ethnicity (p <0.001). In the virus study, those lost to follow-up had higher birth weights (p =0.036) and were less likely to be oxygen dependent at hospital discharge (p =0.003) or be part of a multiple birth (p =0.048). Conclusions: Higher retention was demonstrated when there was regular contact in the follow-up period. Both social factors and initial illness severity affected the retention into follow-up studies of prematurely born infants, though these factors were not consistent across the two studies.KHP Challenge Fund; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College Londo

Improving Estimates of Gross Primary Productivity by Assimilating Solar-Induced Fluorescence Satellite Retrievals in a Terrestrial Biosphere Model Using a Process-Based SIF Model

Abstract Over the last few years, solar-induced chlorophyll fluorescence (SIF) observations from space have emerged as a promising resource for evaluating the spatio-temporal distribution of gross primary productivity (GPP) simulated by global terrestrial biosphere models. SIF can be used to improve GPP simulations by optimizing critical model parameters through statistical Bayesian data assimilation techniques. A prerequisite is the availability of a functional link between GPP and SIF in terrestrial biosphere models. Here we present the development of a mechanistic SIF observation operator in the ORCHIDEE (Organizing Carbon and Hydrology In Dynamic Ecosystems) terrestrial biosphere model. It simulates the regulation of photosystem II fluorescence quantum yield at the leaf level thanks to a novel parameterization of non-photochemical quenching as a function of temperature, photosynthetically active radiation, and normalized quantum yield of photochemistry. It emulates the radiative transfer of chlorophyll fluorescence to the top of the canopy using a parametric simplification of the SCOPE (Soil Canopy Observation Photosynthesis Energy) model. We assimilate two years of monthly OCO-2 (Orbiting Carbon Observatory-2) SIF product at 0.5° (2015?2016) to optimize ORCHIDEE photosynthesis and phenological parameters over an ensemble of grid points for all plant functional types. The impact on the simulated GPP is considerable with a large decrease of the global scale budget by 28 GtC/year over the period 1990?2009. The optimized GPP budget (134/136 GtC/year over 1990?2009/2001?2009) remarkably agrees with independent GPP estimates, FLUXSAT (137 GtC/year over 2001?2009) in particular and FLUXCOM (121 GtC/year over 1990?2009). Our results also suggest a biome dependency of the SIF-GPP relationship that needs to be improved for some plant functional types.Peer reviewe

The validity and reliability of the Breathing Vigilance Questionnaire (Breathe-VQ)

Presented at: British Thoracic Society Winter Meeting 2022, QEII Centre, Broad Sanctuary, Westminster, London SW1P 3EE. Part of the stream: ‘Chariots of fire’ – Interventions and assessment in respiratory physiotherapy.Copyright © Author(s) (or their employer(s)) 2022. Introduction and Objectives: Dysfunctional breathing (DB) is common among people with and without primary respiratory pathology. While anxiety is known to contribute to DB, the underpinning mechanisms are unclear. One likely explanation is that anxiety induces excessive conscious monitoring of breathing, which disrupts ‘automatic’ breathing mechanics. We aimed to validate a new patient-reported outcome measure that allows quantification of such breathing-related ‘hypervigilance’: the Breathing Vigilance Questionnaire (Breathe-VQ). Methods: Three-hundred-and-forty healthy adults (Mean age =27.3 years, range: 18–71; 161 men) were recruited online. The initial Breathe-VQ (11 items, 1–5 Likert scale) was adapted from the Pain Vigilance and Awareness Scale based on feedback from people with and without DB, and expert clinicians and researchers. At baseline all participants completed the Breathe-VQ, background questions, Nijmegen Questionnaire (NQ), Movement Specific Reinvestment Scale and State-Trait Anxiety Inventory (form 2). To assess test-retest reliability, two weeks later 83 people completed the Breathe-VQ again. Validation involved screening of individual items’ behaviour and factor analyses, after which we estimated (retest-)reliability, measurement error, and concurrent/discriminant validity of the finalised Breathe-VQ scale. Results: We removed five items based on item-level and factor analyses. The final six-item Breathe-VQ questionnaire (score range: 6–30) showed excellent internal consistency (ICC=.810) and test-retest reliability (alpha=.892). Minimal detectable change was 6.5 on an individual level, and there were no floor or ceiling effects. Concurrent validity was excellent with significant moderate correlations with measures of general trait anxiety(r’s=.35-.46). Participants at high-risk of having DB (NQ>23; N=76) had significantly higher total scores on the Breathe-VQ (M=19.1, SD=5.4) than low-risk peers (N=225; M=13.8, SD=5.0) p<.001. Further, within this ‘high-risk’ group, Breathe-VQ scores were significantly associated with NQ-scores. Figure 1 shows the final validated Breathe-VQ. Conclusion: The Breathe-VQ is a valid and reliable tool to measure vigilance of breathing. Our data suggest that breathing vigilance may be a contributing factor in DB, and could represent a therapeutic target. Further research is now warranted using the Breathe-VQ in clinical populations of individuals with DB, chronic respiratory disease and COVID-19. Further research could assess the effects of breathing re-training, pulmonary rehabilitation and arts-in-health interventions on vigilance of breathing

The metabolic cost of inspiratory muscle training in mechanically ventilated patients in critical care

Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Supplementary Information is available online at https://icm-experimental.springeropen.com/articles/10.1186/s40635-023-00522-6#Sec19 .Copyright © 2023 The Author(s). Background: Diaphragmatic dysfunction is well documented in patients receiving mechanical ventilation. Inspiratory muscle training (IMT) has been used to facilitate weaning by strengthening the inspiratory muscles, yet the optimal approach remains uncertain. Whilst some data on the metabolic response to whole body exercise in critical care exist, the metabolic response to IMT in critical care is yet to be investigated. This study aimed to quantify the metabolic response to IMT in critical care and its relationship to physiological variables. Methods: We conducted a prospective observational study on mechanically ventilated patients ventilated for ≥ 72 h and able to participate in IMT in a medical, surgical, and cardiothoracic intensive care unit. 76 measurements were taken on 26 patients performing IMT using an inspiratory threshold loading device at 4 cmH2O, and at 30, 50 and 80% of their negative inspiratory force (NIF). Oxygen consumption (VO2) was measured continuously using indirect calorimetry. Results: First session mean (SD) VO2 was 276 (86) ml/min at baseline, significantly increasing to 321 (93) ml/min, 333 (92) ml/min, 351(101) ml/min and 388 (98) ml/min after IMT at 4 cmH2O and 30, 50 and 80% NIF, respectively (p = 0.003). Post hoc comparisons revealed significant differences in VO2 between baseline and 50% NIF and baseline and 80% NIF (p = 0.048 and p = 0.001, respectively). VO2 increased by 9.3 ml/min for every 1 cmH2O increase in inspiratory load from IMT. Every increase in P/F ratio of 1 decreased the intercept VO2 by 0.41 ml/min (CI − 0.58 to − 0.24 p < 0.001). NIF had a significant effect on the intercept and slope, with every 1 cmH2O increase in NIF increasing intercept VO2 by 3.28 ml/min (CI 1.98–4.59 p < 0.001) and decreasing the dose–response slope by 0.15 ml/min/cmH2O (CI − 0.24 to − 0.05 p = 0.002). Conclusions: IMT causes a significant load-dependent increase in VO2. P/F ratio and NIF impact baseline VO2. The dose–response relationship of the applied respiratory load during IMT is modulated by respiratory strength. These data may offer a novel approach to prescription of IMT. Take home message: The optimal approach to IMT in ICU is uncertain; we measured VO2 at different applied respiratory loads to assess whether VO2 increased proportionally with load and found VO2 increased by 9.3 ml/min for every 1 cmH2O increase in inspiratory load from IMT. Baseline NIF has a significant effect on the intercept and slope, participants with a higher baseline NIF have a higher resting VO2 but a less pronounced increase in VO2 as the inspiratory load increases; this may offer a novel approach to IMT prescription. Trial registration: ClinicalTrials.gov, registration number: NCT05101850. Registered on 28 September 2021, https://clinicaltrials.gov/ct2/show/NCT05101850Royal Brompton and Harefield Hospitals Charity Fellowshi

The Importance of Consistent Global Forest Aboveground Biomass Product Validation

Several upcoming satellite missions have core science requirements to produce data for accurate forest aboveground biomass mapping. Largely because of these mission datasets, the number of available biomass products is expected to greatly increase over the coming decade. Despite the recognized importance of biomass mapping for a wide range of science, policy and management applications, there remains no community accepted standard for satellite-based biomass map validation. The Committee on Earth Observing Satellites (CEOS) is developing a protocol to fill this need in advance of the next generation of biomass-relevant satellites, and this paper presents a review of biomass validation practices from a CEOS perspective. We outline the wide range of anticipated user requirements for product accuracy assessment and provide recommendations for the validation of biomass products. These recommendations include the collection of new, high-quality in situ data and the use of airborne lidar biomass maps as tools toward transparent multi-resolution validation. Adoption of community-vetted validation standards and practices will facilitate the uptake of the next generation of biomass products

Improved Respiratory Outcomes for X-Linked Myotubular Myopathy (XLMTM) with Gene Replacement Therapy, Resamirigene Bilparvovec (ASPIRO): Preliminary Results from ASPIRO, a Phase 1/2/3 Study

Astelas Gene Therapies

Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial

Data sharing: Researchers may request access to anonymised participant-level data, trial-level data, and protocols from clinical trials sponsored by Astellas Gene Therapies at [email protected]. For the Astellas criteria on data sharing see https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx.Supplementary Materials are available online at: https://www.sciencedirect.com/science/article/pii/S1474442223003137#sec1 .Copyright © 2023 The Author(s).. Background: X-linked myotubular myopathy is a rare, life-threatening, congenital muscle disease observed mostly in males, which is caused by mutations in MTM1. No therapies are approved for this disease. We aimed to assess the safety and efficacy of resamirigene bilparvovec, which is an adeno-associated viral vector serotype 8 delivering human MTM1. Methods: ASPIRO is an open-label, dose-escalation trial at seven academic medical centres in Canada, France, Germany, and the USA. We included boys younger than 5 years with X-linked myotubular myopathy who required mechanical ventilator support. The trial was initially in two parts. Part 1 was planned as a safety and dose-escalation phase in which participants were randomly allocated (2:1) to either the first dose level (1·3 × 1014 vector genomes [vg]/kg bodyweight) of resamirigene bilparvovec or delayed treatment, then, for later participants, to either a higher dose (3·5 × 1014 vg/kg bodyweight) of resamirigene bilparvovec or delayed treatment. Part 2 was intended to confirm the dose selected in part 1. Resamirigene bilparvovec was administered as a single intravenous infusion. An untreated control group comprised boys who participated in a run-in study (INCEPTUS; NCT02704273) or those in the delayed treatment cohort who did not receive any dose. The primary efficacy outcome was the change from baseline to week 24 in hours of daily ventilator support. After three unexpected deaths, dosing at the higher dose was stopped and the two-part feature of the study design was eliminated. Because of changes to the study design during its implementation, analyses were done on an as-treated basis and are deemed exploratory. All treated and control participants were included in the safety analysis. The trial is registered with ClinicalTrials.gov, NCT03199469. Outcomes are reported as of Feb 28, 2022. ASPIRO is currently paused while deaths in dosed participants are investigated. Findings: Between Aug 3, 2017 and June 1, 2021, 30 participants were screened for eligibility, of whom 26 were enrolled; six were allocated to the lower dose, 13 to the higher dose, and seven to delayed treatment. Of the seven children whose treatment was delayed, four later received the higher dose (n=17 total in the higher dose cohort), one received the lower dose (n=7 total in the lower dose cohort), and two received no dose and joined the control group (n=14 total, including 12 children from INCEPTUS). Median age at dosing or enrolment was 12·1 months (IQR 10·0–30·9; range 9·5–49·7) in the lower dose cohort, 31·1 months (16·0–64·7; 6·8–72·7) in the higher dose cohort, and 18·7 months (10·1–31·5; 5·9–39·3) in the control cohort. Median follow-up was 46·1 months (IQR 41·0–49·5; range 2·1–54·7) for lower dose participants, 27·6 months (24·6–29·1; 3·4–41·0) for higher dose participants, and 28·3 months (9·7–46·9; 5·7–32·7) for control participants. At week 24, lower dose participants had an estimated 77·7 percentage point (95% CI 40·22 to 115·24) greater reduction in least squares mean hours per day of ventilator support from baseline versus controls (p=0·0002), and higher dose participants had a 22·8 percentage point (6·15 to 39·37) greater reduction from baseline versus controls (p=0·0077). One participant in the lower dose cohort and three in the higher dose cohort died; at the time of death, all children had cholestatic liver failure following gene therapy (immediate causes of death were sepsis; hepatopathy, severe immune dysfunction, and pseudomonal sepsis; gastrointestinal haemorrhage; and septic shock). Three individuals in the control group died (haemorrhage presumed related to hepatic peliosis; aspiration pneumonia; and cardiopulmonary failure). Interpretation: Most children with X-linked myotubular myopathy who received MTM1 gene replacement therapy had important improvements in ventilator dependence and motor function, with more than half of dosed participants achieving ventilator independence and some attaining the ability to walk independently. Investigations into the risk for underlying hepatobiliary disease in X-linked myotubular myopathy, and the need for monitoring of liver function before gene replacement therapy, are ongoing.Astellas Gene Therapies