Search

Abstract Fifty million people worldwide are affected by dementia, a heterogeneous neurodegenerative condition encompassing diseases such as Alzheimer’s, vascular dementia, and Parkinson’s. For them, cognitive decline is often the first marker of the pathology after irreversible brain damage has already occurred. Researchers now believe that structural and functional alterations of the brain vasculature could be early precursors of the diseases and are looking at how functional imaging could provide an early diagnosis years before irreversible clinical symptoms. In this preclinical pilot study, we proposed using functional ultrasound (fUS) on the retina to assess neurovascular alterations non-invasively, bypassing the skull limitation. We demonstrated for the first time the use of functional ultrasound in the retina and applied it to characterize the retinal hemodynamic response function in vivo in rats following a visual stimulus. We then demonstrated that retinal fUS could measure robust neurovascular coupling alterations between wild-type rats and TgF344-AD rat models of Alzheimer’s disease. We observed an average relative increase in blood volume of 21% in the WT versus 37% for the TG group (p = 0.019). As a portable, non-invasive and inexpensive technique, rfUS is a promising functional screening tool in clinics for dementia years before symptoms.

The Green Edge project was designed to investigate the onset, life, and fate of a phytoplankton spring bloom (PSB) in the Arctic Ocean. The lengthening of the ice-free period and the warming of seawater, amongst other factors, have induced major changes in Arctic Ocean biology over the last decades. Because the PSB is at the base of the Arctic Ocean food chain, it is crucial to understand how changes in the Arctic environment will affect it. Green Edge was a large multidisciplinary, collaborative project bringing researchers and technicians from 28 different institutions in seven countries together, aiming at understanding these changes and their impacts on the future. The fieldwork for the Green Edge project took place over two years (2015 and 2016) and was carried out from both an ice camp and a research vessel in Baffin Bay, in the Canadian Arctic. This paper describes the sampling strategy and the dataset obtained from the research cruise, which took place aboard the Canadian Coast Guard ship (CCGS) Amundsen in late spring and early summer 2016. The sampling strategy was designed around the repetitive, perpendicular crossing of the marginal ice zone (MIZ), using not only ship-based station discrete sampling but also high-resolution measurements from autonomous platforms (Gliders, BGC-Argo floats …) and under-way monitoring systems. The dataset is available at https://doi.org/10.17882/86417 (Bruyant et al., 2022).

The characteristics of the CISE-LOCEAN seawater isotope dataset (δ18O, δ2H, referred to as δD) are presented (https://doi.org/10.17882/71186; Waterisotopes-CISE-LOCEAN, 2021). This dataset covers the time period from 1998 to 2021 and currently includes close to 8000 data entries, all with δ18O, three-quarters of them also with δD, associated with a date stamp, space stamp, and usually a salinity measurement. Until 2010, samples were analyzed by isotopic ratio mass spectrometry and since then mostly by cavity ring-down spectroscopy (CRDS). Instrumental uncertainty in this dataset is usually as low as 0.03 ‰ for δ18O and 0.15 ‰ for δD. An additional uncertainty is related to the isotopic composition of the in-house standards that are used to convert data to the Vienna Standard Mean Ocean Water (VSMOW) scale. Different comparisons suggest that since 2010 the latter have remained within at most 0.03 ‰ for δ18O and 0.20 ‰ for δD. Therefore, combining the two uncertainties suggests a standard deviation of at most 0.05 ‰ for δ18O and 0.25 ‰ for δD. For some samples, we find that there has been evaporation during collection and storage, requiring adjustment of the isotopic data produced by CRDS, based on d-excess (δD − 8×δ18O). This adjustment adds an uncertainty in the respective data of roughly 0.05 ‰ for δ18O and 0.10 ‰ for δD. This issue of conservation of samples is certainly a strong source of quality loss for parts of the database, and “small” effects may have remained undetected. The internal consistency of the database can be tested for subsets of the dataset when time series can be obtained (such as in the southern Indian Ocean or North Atlantic subpolar gyre). These comparisons suggest that the overall uncertainty of the spatially (for a cruise) or temporally (over a year) averaged data is less than 0.03 ‰ for δ18O and 0.15 ‰ for δD. However, 18 comparisons with duplicate seawater data analyzed in other laboratories or with other datasets in the intermediate and deep ocean suggest a larger scatter. When averaging the 18 comparisons done for δ18O, we find a difference of 0.082 ‰ with a standard error of 0.016 ‰. Such an average difference is expected due to the adjustments applied at LOCEAN to saline water data produced either by CRDS or isotope ratio mass spectrometry (IRMS), but the scatter found suggests that care is needed when merging datasets from different laboratories. Examples of time series in the surface North Atlantic subpolar gyre illustrate the temporal changes in water isotope composition that can be detected with a carefully validated dataset.

Background and Aims Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR). Methods In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo. Clinical responders were randomized to subcutaneous risankizumab 180 mg, risankizumab 360 mg, or placebo (risankizumab withdrawal) in the 52-week phase 3 COMMAND maintenance study. This post hoc analysis assessed outcomes by AT-IR status, number, and mechanism of action. AT included biologics, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators. Results Efficacy analyses included 472 non-AT-IR and 503 AT-IR patients (induction), and 137 non-AT-IR and 411 AT-IR patients (maintenance). More patients achieved clinical remission per Adapted Mayo score with risankizumab 1200 mg versus placebo at induction week 12 (non-AT-IR, 29.7% versus 8.4%, nominal P  < .0001; AT-IR, 11.4% versus 4.3%, nominal P  = .0083); consistent with risankizumab 180 mg or risankizumab 360 mg versus placebo (withdrawal) at maintenance week 52 (non-AT-IR, 50.9% or 61.7% versus 31.1%, nominal P  = .057 or P  = .0033, respectively; AT-IR, 36.6% or 29.5% versus 23.2%, nominal P  = .0159 or P  = .2334, respectively). Risankizumab had increased efficacy over placebo, regardless of AT-IR number or mechanism of action, with higher efficacy rates for non-AT-IR compared to AT-IR. Safety results in non-AT-IR and AT-IR patients were generally comparable in both induction and maintenance. Conclusions Risankizumab was effective and well tolerated, regardless of prior AT-IR status. Clinical trial registration numbers INSPIRE [ NCT03398148 ], COMMAND [ NCT03398135 ]. [ABSTRACT FROM AUTHOR]

The French electricity mix is dominated by nuclear power, representing 69% of the power generation in 2021, and further development of nuclear power for electricity is expected. This study applied Life Cycle Assessment (LCA) to evaluate the potential environmental impact of nuclear power generated by EDF SA., the world’s largest nuclear operator and electric utility company operating all the nuclear reactors in France. The study’s main objective was to assess the potential environmental impacts of nuclear power, from raw material extraction to end-of-life, according to several indicators, while focusing on the climate change indicator. The total impact of nuclear power on climate change (3.7 gCO2eq/kWh) is found to be in the lower range of LCA studies on nuclear power conducted so far. Mining and milling of uranium are the most contributing stages, while EDF’s electricity generation is the second largest contributor. The key output of this LCA is the extensive data collected, resulting in a detailed LCA model covering the entire French nuclear fleet. Future studies should focus on (1) collecting more specific data on uranium mining and processing, as these are so far based on database data, and (2) addressing other LCA indicators, such as water use, land use, and ecotoxicity.

Planetary protection is a set of measures agreed upon at an international level to ensure the protection of scientific investigation during space exploration. As space becomes more accessible with traditional and new actors launching complex and innovative projects that involve robotics (including sample return) and human exploration, we have the responsibility to protect the pristine environments that we explore and our own biosphere. In this sense, the Committee on Space Research (COSPAR) provides the international standard for planetary protection as well as a forum for international consultation. COSPAR has formulated a Planetary Protection Policy with associated requirements for responsible space exploration. Although not legally binding under international law, the standard offered by the Policy with its associated requirements is internationally endorsed along with implementation guidelines supplied for reference in support States’ compliance with Article IX of the United Nations Outer Space Treaty of 1967. Indeed, States parties to the Outer Space Treaty (under Article VI) are responsible for any space activities in their countries, governmental and non-governmental. The main goal of this Policy is to avoid compromising the search for any lifeforms on other celestial bodies and to protect the Earth from a potential threat posed by extraterrestrial samples returned by an interplanetary mission. The COSPAR Planetary Protection Policy has defined five categories, depending on the target and objective of the specific space mission. Associated to these categories are requirements are various degrees of rigor in the contamination control applied. The Policy is assessed regularly and updated with input from new scientific findings and in conjunction with the fast-evolving space exploration milieu. The COSPAR Panel on Planetary Protection (PPP) is a designated international committee composed of scientists, agency representatives and space experts. Its role is to support and revise the COSPAR Policy and its related requirements (https://cosparhq.cnes.fr/scientific-structure/panels/panel-on-planetary-protection-ppp/). The Panel’s activities deal with the individual needs of a space mission while exercising swift care and expertise to ensure sustainable exploration of the Solar System.

Background Right heart catheterization (RHC) is a high‐risk procedure in children with pulmonary arterial hypertension without clear guidelines for the indications and targets of invasive reassessment. Our objectives are to define the aims of repeated RHC and evaluate the correlation between noninvasive criteria and hemodynamic parameters. Methods and Results Clinical and hemodynamic characteristics from 71 incident treatment‐naïve children (median age 6.2 years) with pulmonary arterial hypertension who had a baseline and reevaluation RHC were analyzed. Correlations between noninvasive predictors and hemodynamic parameters were tested. Adverse outcomes were defined as death, lung transplantation, or Potts shunt. At baseline, pulmonary vascular resistance index (hazard ratio [HR] 1.07 per 1 WU·m2 increase [95% CI, 1.02–1.12], P=0.002), stroke volume index (HR 0.95 per 1 L·min−1·m−2 increase [95% CI, 0.91–0.99], P=0.012), pulmonary artery compliance index (HR 0.16 per 1 mL·mm Hg−1·m−2 increase [95% CI, 0.051–0.52], P=0.002), and right atrial pressure (HR, 1.31 per 1 mm Hg increase [95% CI, 1.01–1.71], P=0.043) were associated with adverse outcomes. Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure were still associated with a worse outcome at second RHC. Noninvasive criteria accurately predicted hemodynamic evolution; however, 70% of the patients who had improved based on noninvasive criteria still presented at least 1 “at risk” hemodynamics at second RHC. Conclusions Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure are solid predictors of adverse outcomes in pediatric pulmonary arterial hypertension and potential therapeutic targets. Noninvasive criteria accurately predict the evolution of hemodynamic parameters, but insufficiently. Repeated RHC are helpful to identify children with persistent higher risk after treatment introduction.

BackgroundAir pollution exposure is associated with acute exacerbation, disease progression, and mortality in patients with idiopathic pulmonary fibrosis (IPF). The objective of this study was to describe the impact of air pollution exposures on disease severity, as well as changes in lung function, in patients with IPF.MethodsUsing home spirometers and symptom diaries, 25 patients with IPF prospectively recorded FVC weekly for up to 40 weeks. Residential addresses were geocoded to estimate weekly mean air pollution exposures for ground-level ozone (O3), nitrogen dioxide (NO2), and particulate matter < 2.5 or 10 μm in aerodynamic diameter (PM2.5 and PM10, respectively). The dependence of weekly clinical measurements on preceding levels of each pollutant was assessed with the use of linear mixed models, yielding beta-coefficients with 95% CIs, using varying lag times.ResultsLower mean FVC % predicted was consistently associated with increased mean exposures to PM10 in the 2 to 5 weeks preceding clinical measurements (range, -0.46 to -0.39 [95% CI, -0.73 to -0.13]; P < .005). Lower mean FVC % predicted over the study period was inversely related to mean levels of NO2 (-0.45 [95% CI, -0.85 to -0.05]; P = .03), PM2.5 (-0.45 [95% CI, -0.84 to -0.07]; P = .02), and PM10 (-0.57 [95% CI, -0.92 to -0.21]; P = .003), averaged over the study. Weekly changes in FVC and changes over 40 weeks were independent of pollution exposures.ConclusionsHigher air pollution exposures were associated with lower lung function, but not changes in lung function, in patients with IPF. Further studies are needed to characterize the mechanisms underlying this relationship.

RationalePrior work has described the experience of caregiving in idiopathic pulmonary fibrosis, but the effect on caregivers in interstitial lung disease (ILD) has not been explored.ObjectivesDescribe the burden, resilience, and health related quality of life (HRQoL) of caregivers of people with ILD.MethodsIn a mixed methods study, ILD caregivers completed questionnaires and participated in focus groups. A qualitative thematic analysis of the focus group transcripts was conducted.ResultsThirty seven caregivers completed the survey, and 15 participated in the focus groups. 65% were female; the average age was 66 (SD = 13). The mean Short Form-36 role emotional and mental health scores were 18 (SD = 4) and 46 (SD = 7). The focus groups identified 4 major themes: emotional burden, changes in relationship, coping strategies, and unmet needs of caregivers.ConclusionsCaregiving for patients with ILD significantly impairs HRQoL, particularly, emotional health. Increasing resources could improve the caregiving experience in ILD.

RationaleCurrent diagnosis of chronic hypersensitivity pneumonitis (cHP) involves considering a combination of clinical, radiological, and pathological information in multidisciplinary team discussions. However, this approach is highly variable with poor agreement between centers.ObjectivesWe aimed to identify diagnostic criteria for cHP that reach consensus among international experts.MethodsA 3-round modified Delphi survey was conducted between April and August 2017. Forty-five experts in interstitial lung disease from 14 countries participated in the online survey. Diagnostic items included in round 1 were generated using expert interviews and literature review. During rounds 1 and 2, experts rated the importance of each diagnostic item on a 5-point Likert scale. The a priori threshold of consensus was ≥ 75% of experts rating a diagnostic item as very important or important. In the third round, experts graded the items that met consensus as important and provided their level of diagnostic confidence for a series of clinical scenarios.Measurements and main resultsConsensus was achieved on 18 of the 40 diagnostic items. Among these, experts gave the highest level of importance to the identification of a causative antigen, time relation between exposure and disease, mosaic attenuation on chest imaging, and poorly formed non-necrotizing granulomas on pathology. In clinical scenarios, the diagnostic confidence of experts in cHP was heightened by the presence of these diagnostic items.ConclusionThis consensus-based approach for the diagnosis of cHP represents a first step towards the development of international guidelines for the diagnosis of cHP.