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Abstract In multiple myeloma, as in B‐cell malignancies, mono‐ and especially bi‐allelic TP53 gene inactivation is a high‐risk factor for treatment resistance, and there are currently no therapies specifically targeting p53 deficiency. In this study, we evaluated if the loss of cell cycle control in p53‐deficient myeloma cells would confer a metabolically actionable vulnerability. We show that CTP synthase 1 (CTPS1), which encodes a CTP synthesis rate‐limiting enzyme essential for DNA and RNA synthesis in lymphoid cells, is overexpressed in samples from myeloma patients displaying a high proliferation rate (high MKI67 expression) or a low p53 score (synonymous with TP53 deletion and/or mutation). This overexpression of CTPS1 was associated with reduced survival in two cohorts. Using scRNA‐seq analysis in 24 patient samples, we further demonstrate that myeloma cells in the S or G2/M phase display high CTPS1 expression. Pharmacological inhibition of CTPS1 by STP‐B induced cell cycle arrest in early S phase in isogenic NCI‐H929 or XG7 TP53+/+, TP53−/−, and TP53R175H/R175H cells and in a TP53−/R123STOP patient sample. The functional annotation of transcriptional changes in 10 STP‐B‐treated myeloma cell lines revealed a decrease in protein translation and confirmed the blockade of cells into the S phase. The pharmacological inhibition of ATR, which governs the intrinsic S/G2 checkpoint, in STP‐B‐induced S‐phase arrested cells synergistically induced cell death in TP53+/+, TP53−/−, and TP53R175H/R175H isogenic cell lines (Bliss score >15). This combination induced replicative stress and caspase‐mediated cell death and was highly effective in resistant/refractory patient samples with TP53 deletion and/or mutation and in TP53−/− NCI‐H929 xenografted NOD‐scid IL2Rgamma mice. Our in vitro, ex vivo, and in vivo data provide the rationale for combined CTPS1 and ATR inhibition for the treatment of p53‐deficient patients.

Abstract Mycobacterium abscessus (MABS) displays differential subspecies susceptibility to macrolides. Thus, identifying MABS's subspecies (M. abscessus, M. bolletii and M. massiliense) is a clinical necessity for guiding treatment decisions. We aimed to assess the potential of Machine Learning (ML)‐based classifiers coupled to Matrix‐Assisted Laser Desorption/Ionization Time‐of‐Flight (MALDI‐TOF) MS to identify MABS subspecies. Two spectral databases were created by using 40 confirmed MABS strains. Spectra were obtained by using MALDI‐TOF MS from strains cultivated on solid (Columbia Blood Agar, CBA) or liquid (MGIT®) media for 1 to 13 days. Each database was divided into a dataset for ML‐based pipeline development and a dataset to assess the performance. An in‐house programme was developed to identify discriminant peaks specific to each subspecies. The peak‐based approach successfully distinguished M. massiliense from the other subspecies for strains grown on CBA. The ML approach achieved 100% accuracy for subspecies identification on CBA, falling to 77.5% on MGIT®. This study validates the usefulness of ML, in particular the Random Forest algorithm, to discriminate MABS subspecies by MALDI‐TOF MS. However, identification in MGIT®, a medium largely used in mycobacteriology laboratories, is not yet reliable and should be a development priority.

Abstract Clostridioides difficile (CD) infections are defined by toxins A (TcdA) and B (TcdB) along with the binary toxin (CDT). The emergence of the ‘hypervirulent’ (Hv) strain PR 027, along with PR 176 and 181, two decades ago, reshaped CD infection epidemiology in Europe. This study assessed MALDI‐TOF mass spectrometry (MALDI‐TOF MS) combined with machine learning (ML) and Deep Learning (DL) to identify toxigenic strains (producing TcdA, TcdB with or without CDT) and Hv strains. In total, 201 CD strains were analysed, comprising 151 toxigenic (24 ToxA+B+CDT+, 22 ToxA+B+CDT+ Hv+ and 105 ToxA+B+CDT−) and 50 non‐toxigenic (ToxA−B−) strains. The DL‐based classifier exhibited a 0.95 negative predictive value for excluding ToxA−B− strains, showcasing accuracy in identifying this strain category. Sensitivity in correctly identifying ToxA+B+CDT− strains ranged from 0.68 to 0.91. Additionally, all classifiers consistently demonstrated high specificity (>0.96) in detecting ToxA+B+CDT+ strains. The classifiers' performances for Hv strain detection were linked to high specificity (≥0.96). This study highlights MALDI‐TOF MS enhanced by ML techniques as a rapid and cost‐effective tool for identifying CD strain virulence factors. Our results brought a proof‐of‐concept concerning the ability of MALDI‐TOF MS coupled with ML techniques to detect virulence factor and potentially improve the outbreak's management.

Abstract Camera traps deployed with olfactory attractants are used to survey rare and elusive carnivores. Study areas with deep snowpack and rugged terrain present challenges and risks to field personnel, who traditionally must revisit camera stations regularly to refresh attractants. In such locations, alternative overwinter survey protocols that include a persistent attractant would improve both the safety and efficiency of camera‐trap surveys. We present a protocol for installing camera traps and automated scent dispensers on trees at above‐average maximum snow depth to eliminate the need for interim service visits and to enable standardized surveys to be conducted throughout the year. Our protocol proved to be effective at attracting and detecting numerous and repeated visits by wolverines, fishers, and other carnivores in two montane regions of the western contiguous United States. The volume, timing, and composition of liquid scent lure released by automated scent dispensers can be varied to target multiple species of interest, and the dispenser can be used in situations where bait rewards may influence the behavior of target species and/or pose human safety concerns.

Abstract Tropical forests are a major component of the global carbon cycle and home to two‐thirds of terrestrial species. Upper‐canopy trees store the majority of forest carbon and can be vulnerable to drought events and storms. Monitoring their growth and mortality is essential to understanding forest resilience to climate change, but in the context of forest carbon storage, large trees are underrepresented in traditional field surveys, so estimates are poorly constrained. Aerial photographs provide spectral and textural information to discriminate between tree crowns in diverse, complex tropical canopies, potentially opening the door to landscape monitoring of large trees. Here we describe a new deep convolutional neural network method, Detectree2, which builds on the Mask R‐CNN computer vision framework to recognize the irregular edges of individual tree crowns from airborne RGB imagery. We trained and evaluated this model with 3797 manually delineated tree crowns at three sites in Malaysian Borneo and one site in French Guiana. As an example application, we combined the delineations with repeat lidar surveys (taken between 3 and 6 years apart) of the four sites to estimate the growth and mortality of upper‐canopy trees. Detectree2 delineated 65 000 upper‐canopy trees across 14 km2 of aerial images. The skill of the automatic method in delineating unseen test trees was good (F1 score = 0.64) and for the tallest category of trees was excellent (F1 score = 0.74). As predicted from previous field studies, we found that growth rate declined with tree height and tall trees had higher mortality rates than intermediate‐size trees. Our approach demonstrates that deep learning methods can automatically segment trees in widely accessible RGB imagery. This tool (provided as an open‐source Python package) has many potential applications in forest ecology and conservation, from estimating carbon stocks to monitoring forest phenology and restoration. Python package available to install at https://github.com/PatBall1/Detectree2.

Abstract Background The hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are connective tissue disorders characterized by generalized joint hypermobility, associated with chronic pain and several symptoms, such as fatigue, dysautonomia, as well as psychiatric co‐morbidities. Clinical observations of unusual manifestations during systematic sensory testing raised the question of a possible co‐existence with a functional neurological disorder (FND). Hence, this study aimed to assess the presence of positive functional neurological signs (FNS) in a cohort of patients with hEDS/HSD. Methods The clinical data of hEDS/HSD patients (N = 24) were retrospectively analyzed and compared to a prospectively recruited age‐/sex‐matched healthy control group (N = 22). Four motor‐ and three sensory‐positive FNS were assessed. Results Twenty‐two patients (92%) presented at least one motor or sensory FNS. Five patients (21%) presented only a single FNS, 14 presented between 2 and 4 FNS (58%), and 3 patients presented 5 or more FNS (12%). None of the healthy controls presented motor FNS, and only two presented a sensory FNS. Conclusions The presence of FNS in hEDS/HSD deserves better clinical detection and formal diagnosis of FND to offer more adequate care in co‐morbid situations. In fact, FND can severely interfere with rehabilitation efforts in hEDS/HSD, and FND‐targeted physical therapy should perhaps be combined with EDS/HSD‐specific approaches.

Abstract Rapid and simple estimation of the mass eruption rate (MER) from column height is essential for real‐time volcanic hazard management and reconstruction of past explosive eruptions. Using 134 eruptive events from the new Independent Volcanic Eruption Source Parameter Archive (IVESPA, v1.0), we explore empirical MER‐height relationships for four measures of column height: spreading level, sulfur dioxide height, and top height from direct observations and as reconstructed from deposits. These relationships show significant differences and highlight limitations of empirical models currently used in operational and research applications. The roles of atmospheric stratification, wind, and humidity remain challenging to detect across the wide range of eruptive conditions spanned in IVESPA, ultimately resulting in empirical relationships outperforming analytical models that account for atmospheric conditions. This finding highlights challenges in constraining the MER‐height relation using heterogeneous observations and empirical models, which reinforces the need for improved eruption source parameter data sets and physics‐based models.

Abstract Standard climate projections represent future volcanic eruptions by a constant forcing inferred from 1850 to 2014 volcanic forcing. Using the latest ice‐core and satellite records to design stochastic eruption scenarios, we show that there is a 95% probability that explosive eruptions could emit more sulfur dioxide (SO2) into the stratosphere over 2015–2100 than current standard climate projections (i.e., ScenarioMIP). Our simulations using the UK Earth System Model with interactive stratospheric aerosols show that for a median future eruption scenario, the 2015–2100 average global‐mean stratospheric aerosol optical depth (SAOD) is double that used in ScenarioMIP, with small‐magnitude eruptions (

Societal Impact Statement Reading and writing DNA is now possible with an unprecedented speed and ease. To catch up with digitization of genetic resources, scientists need to join with all relevant stakeholders and design new global governance mechanisms for digital sequence information. We propose the establishment of a Multi‐stakeholder Committee on the Governance of Digital Sequence Information (DSI). This multi‐disciplinary body will be dedicated to mitigate governance issues associated with the digitization of genetic resources. Solving the DSI conundrum is sorely needed given the forthcoming multilateral meetings of the Access and Benefit Sharing (ABS) framework (the next CBD COP is scheduled in 2021) that are central to tackle the global loss of biodiversity, global warming, pandemic risk and food insecurity. Summary Contemporary research is increasingly data‐centric and the rise of genomics revolutionized our approach and use of genetic resources. However, genomics developed relatively independently from the international instruments on the conservation of biological diversity, in particular the Access and Benefit Sharing (ABS) framework. The legal and political status of Digital Sequence Information (DSI) derived from genetic resources emerged recently as a contentious point in the various ABS instruments dealing with genetic resources. In view of the multiple parallel and uncoordinated debates that occurred in various forums dealing with plants, animals, terrestrial, microbial, marine and agricultural biodiversity, we propose here to take a step back in the discussion. We argue that DSI should be considered as an overarching issue to be addressed through a coordinated and inclusive Multi‐stakeholder Committee that would assess its position and role within the existing ABS regime complex. This Multi‐stakeholder Committee on the Governance of Digital Sequence Information, that may run under the auspices of the United Nations, will be dedicated to mitigate global governance issues associated with the digitization of genetic resources. In this paper, we sketch this body as a transversal and inclusive tool to facilitate long‐term coherence in all ABS policy forums.

Abstract Disposing efficiently and safely chlorophyll derivatives during senescence requires a coordinated pathway that is well conserved throughout green plants. The PAO/phyllobilin pathway catalyzes the degradation of the chlorophyll during senescence and allows detoxification of the pigment and its subsequent export from the chloroplast. Although most of the chloroplastic reactions involved in chlorophyll degradation are well understood, the diversity of enzymes responsible for downstream modifications of non‐phototoxic phyllobilins remains to be explored. More than 40 phyllobilins have been described to date, but only three enzymes catalyzing side‐chain reactions have been identified in Arabidopsis thaliana, namely, TIC55, CYP89A9, and MES16. Here, by generating a triple mutant, we evaluate the extent to which these enzymes are influencing the rate and amplitude of chlorophyll degradation at the metabolite as well as its regulation at the transcriptome level. Our data show that major side‐chain modifications of phyllobilins do not influence significantly chlorophyll degradation or leaf senescence, letting the physiological relevance of their striking diversity an open question.

Abstract The global amphibian crisis is driven by a range of stressors including disease, habitat loss, and environmental contamination. The role of climate change remains poorly studied and is likely to influence environmental suitability, ranges, reproduction, and phenology. This study aimed to characterize the bioclimatic‐habitat niche space of the Natterjack toad (Epidalea calamita) throughout its European range and to assess the impact of climate on the toad's environmental suitability and breeding behavior in Ireland, where declines in recent decades have resulted in it being regionally Red‐Listed as Endangered. To address these questions, we first identified which climate variables best predict the current bioclimatic niche, fecundity (number of eggs deposit), and phenology. We then used future climate projections for two time periods (2041–2060 and 2061–2080) and two greenhouse gas emission scenarios (RCP 4.5 and RCP 8.5) to predict how the species range, fecundity, and phenology would change. The European range of the species was found to be limited by winter temperatures while its bioclimatic niche varied markedly throughout its range. Species distribution models suggested projected climate change will increase environmental suitability for the species throughout its range, including Ireland, but most notably in Scandinavia and the Baltic. Fecundity in Ireland was greatest during the cool temperatures of spring and after wet winters associated with ephemeral breeding pool availability. Warm, dry summers in the preceding year influenced fecundity the following spring indicative of carryover effects. Initiation of spawning was driven by spring temperatures, not rainfall. Projections suggested future climate change may increase fecundity in Ireland while spawning may commence earlier throughout the 21st century especially under a high greenhouse gas emission scenario (RCP 8.5). Despite recent range contraction and population declines due to habitat deterioration, the Natterjack toad, if subject to a suitable species conservation strategy, has the potential to be a climate change winner, notwithstanding unpredictable habitat and land‐use change, sea‐level rise inducing coastal erosion, changes in invertebrate prey abundance, and disease.

Abstract Maternal characteristics, social dynamics, and environmental factors can all influence reproduction and survival and shape trade‐offs that might arise between these components of fitness. Short‐lived mammals like the golden‐mantled ground squirrel (GMGS; Callospermophilus lateralis) tend to maximize effort toward current reproduction at the expense of survival but may be complicated by other aspects of the species’ life history and environment. Here, we use 25 years of data (1995–2020) collected from a population of GMGS at the Rocky Mountain Biological Research Laboratory in Gothic, Colorado, to test the effect of several maternal characteristics (e.g., age, experience, and timing of litter emergence), social context (e.g., litter sex ratio and kin density), and environmental context (e.g., date of bare ground and length of vegetative growing season) on survival of reproductive female GMGS using Cox proportional hazard models. Our results indicated that social dynamics (i.e., density) and environmental conditions (i.e., standardized first day of permanent snow cover and length of growing season) explained significant variation in annual maternal survival, while maternal characteristics did not. A higher density of related breeding females and the total number of females (both related and unrelated to the focal mother) were associated with an increase in the mortality hazard. A later standardized date of the first day of permanent snow cover and a shorter growing season both reduced the maternal mortality hazard. Together, our results suggest that factors extrinsic to the squirrels affect maternal survival and thus may also influence local population growth and dynamics in GMGS and other short‐lived, territorial mammal species.

Abstract Wildfire occurrence and severity is predicted to increase in the upcoming decades with severe negative impacts on human societies. The impacts of upwind wildfire activity on glacier melt, a critical source of freshwater for downstream environments, were investigated through analysis of field and remote sensing observations and modeling experiments for the 2015–2020 melt seasons at the well‐instrumented Athabasca Glacier in the Canadian Rockies. Upwind wildfire activity influenced surface glacier melt through both a decrease in the surface albedo from deposition of soot on the glacier and through the impact of smoke on atmospheric conditions above the glacier. Athabasca Glacier on‐ice weather station observations show days with dense smoke were warmer than clear, non‐smoky days, and sustained a reduction in surface shortwave irradiance of 103 W m−2 during peak shortwave irradiance and an increase in longwave irradiance of 10 W m−2, producing an average 15 W m−2 decrease in net radiation. Albedo observed on‐ice gradually decreased after the wildfires started, from a summer average of 0.29 in 2015 before the wildfires to as low as 0.16 in 2018 after extensive wildfires and remained low for two more melt seasons without substantial upwind wildfires. Reduced all‐wave irradiance partly compensated for the increase in melt due to lowered albedo in those seasons when smoke was detected above Athabasca Glacier. In melt seasons without smoke, the suppressed albedo increased melt by slightly more than 10% compared to the simulations without fire‐impacted albedo, increasing melt by 0.42 m. w.e. in 2019 and 0.37 m. w.e. in 2020.

Abstract Introduction Intellectually gifted children have higher performance in many domains of attention than intellectually average children. However, these empirical findings are not consistent in the literature. Few studies investigated the characteristics of alerting, orienting, and executive control networks in intellectually gifted children. The aim of our study was to investigate their characteristics of attentional abilities compared to intellectually average children. Method Fifty‐five intellectually gifted children (age range 8–14 years old) were compared to 55 intellectually average children (age range 8–14 years old) using the Attention Network Test (ANT) to assess these three attentional constructs. Results Intellectually gifted children made fewer errors than intellectually average children in the processing of the ANT. In terms of attention network scores, they also outperformed intellectually average children in executive control only. Conclusion Intellectually gifted children do not differ from intellectual average children in terms of the speed of processing in a speeded task such as ANT, but they stand out in terms of accuracy of processing. Intellectually gifted children have better ability to focus volitionally in order to solve a simple perceptual conflict than intellectually average children.

Abstract Background Homelessness has emerged as a public health priority, with growing numbers of vulnerable populations despite advances in social welfare. In February 2020, the United Nations passed a historic resolution, identifying the need to adopt social‐protection systems and ensure access to safe and affordable housing for all. The establishment of housing stability is a critical outcome that intersects with other social inequities. Prior research has shown that in comparison to the general population, people experiencing homelessness have higher rates of infectious diseases, chronic illnesses, and mental‐health disorders, along with disproportionately poorer outcomes. Hence, there is an urgent need to identify effective interventions to improve the lives of people living with homelessness. Objectives The objective of this systematic review is to identify, appraise, and synthesise the best available evidence on the benefits and cost‐effectiveness of interventions to improve the health and social outcomes of people experiencing homelessness. Search Methods In consultation with an information scientist, we searched nine bibliographic databases, including Medline, EMBASE, and Cochrane CENTRAL, from database inception to February 10, 2020 using keywords and MeSH terms. We conducted a focused grey literature search and consulted experts for additional studies. Selection Criteria Teams of two reviewers independently screened studies against our inclusion criteria. We included randomised control trials (RCTs) and quasi‐experimental studies conducted among populations experiencing homelessness in high‐income countries. Eligible interventions included permanent supportive housing (PSH), income assistance, standard case management (SCM), peer support, mental health interventions such as assertive community treatment (ACT), intensive case management (ICM), critical time intervention (CTI) and injectable antipsychotics, and substance‐use interventions, including supervised consumption facilities (SCFs), managed alcohol programmes and opioid agonist therapy. Outcomes of interest were housing stability, mental health, quality of life, substance use, hospitalisations, employment and income. Data Collection and Analysis Teams of two reviewers extracted data in duplicate and independently. We assessed risk of bias using the Cochrane Risk of Bias tool. We performed our statistical analyses using RevMan 5.3. For dichotomous data, we used odds ratios and risk ratios with 95% confidence intervals. For continuous data, we used the mean difference (MD) with a 95% CI if the outcomes were measured in the same way between trials. We used the standardised mean difference with a 95% CI to combine trials that measured the same outcome but used different methods of measurement. Whenever possible, we pooled effect estimates using a random‐effects model. Main Results The search resulted in 15,889 citations. We included 86 studies (128 citations) that examined the effectiveness and/or cost‐effectiveness of interventions for people with lived experience of homelessness. Studies were conducted in the United States (73), Canada (8), United Kingdom (2), the Netherlands (2) and Australia (1). The studies were of low to moderate certainty, with several concerns regarding the risk of bias. PSH was found to have significant benefits on housing stability as compared to usual care. These benefits impacted both high‐ and moderate‐needs populations with significant cimorbid mental illness and substance‐use disorders. PSH may also reduce emergency department visits and days spent hospitalised. Most studies found no significant benefit of PSH on mental‐health or substance‐use outcomes. The effect on quality of life was also mixed and unclear. In one study, PSH resulted in lower odds of obtaining employment. The effect on income showed no significant differences. Income assistance appeared to have some benefits in improving housing stability, particularly in the form of rental subsidies. Although short‐term improvement in depression and perceived stress levels were reported, no evidence of the long‐term effect on mental health measures was found. No consistent impact on the outcomes of quality of life, substance use, hospitalisations, employment status, or earned income could be detected when compared with usual services. SCM interventions may have a small beneficial effect on housing stability, though results were mixed. Results for peer support interventions were also mixed, though no benefit was noted in housing stability specifically. Mental health interventions (ICM, ACT, CTI) appeared to reduce the number of days homeless and had varied effects on psychiatric symptoms, quality of life, and substance use over time. Cost analyses of PSH interventions reported mixed results. Seven studies showed that PSH interventions were associated with increased cost to payers and that the cost of the interventions were only partially offset by savings in medical‐ and social‐services costs. Six studies revealed that PSH interventions saved the payers money. Two studies focused on the cost‐effectiveness of income‐assistance interventions. For each additional day housed, clients who received income assistance incurred additional costs of US$45 (95% CI, −$19, −$108) from the societal perspective. In addition, the benefits gained from temporary financial assistance were found to outweigh the costs, with a net savings of US$20,548. The economic implications of case management interventions (SCM, ICM, ACT, CTI) was highly uncertain. SCM clients were found to incur higher costs than those receiving the usual care. For ICM, all included studies suggested that the intervention may be cost‐offset or cost‐effective. Regarding ACT, included studies consistently revealed that ACT saved payers money and improved health outcomes than usual care. Despite having comparable costs (US$52,574 vs. US$51,749), CTI led to greater nonhomeless nights (508 vs. 450 nights) compared to usual services. Authors' Conclusions PSH interventions improved housing stability for people living with homelessness. High‐intensity case management and income‐assistance interventions may also benefit housing stability. The majority of included interventions inconsistently detected benefits for mental health, quality of life, substance use, employment and income. These results have important implications for public health, social policy, and community programme implementation. The COVID‐19 pandemic has highlighted the urgent need to tackle systemic inequality and address social determinants of health. Our review provides timely evidence on PSH, income assistance, and mental health interventions as a means of improving housing stability. PSH has major cost and policy implications and this approach could play a key role in ending homelessness. Evidence‐based reviews like this one can guide practice and outcome research and contribute to advancing international networks committed to solving homelessness.

Abstract The ancient solar energetic particle (SEP) events of 774/775 CE and 993/994 CE were characterized thanks to radionuclide productions stored in environmental archives as ice cores or tree rings. Primary cosmic ray spectra deduced from these cosmogenic isotope data indicate that the impact of these extreme SEP events would have been much more significant than any of the ones observed during the modern era. However, the impact of these should be studied more accurately in the framework of the ambient dose equivalent impacting aircrew and passengers in the air traffic context by considering physical parameters such as time profile or anisotropy properties. In this study, the impact that 774/775 CE and 993/994 CE past extreme SEP events could have had on modern air traffic is discussed. Possible event spectra for these ancient events are derived from the spectra ground‐level enhancement (GLE) 5 and GLE 69, which have been observed during the modern era and have been widely studied/characterized using measurements. The investigations include the impact of the SEP activity on ambient dose equivalent, including detailed analyses considering route, airplane characteristics (departure, arrival, continent, airplane type), and the time occurrence of the SEP event. Statistical analyses show that additional dose levels can reach values on the order of 70 mSv, which is absolutely significant considering the current air traffic recommendations. The orders of magnitude of the ambient dose equivalent induced during past extreme SEP events raises a number of issues, both for aircrews and for avionics hardware. This study demonstrates that simulations can be useful for the evaluation of risks in case of extreme SEP events.

Background With the emergence of coronary computed tomography (CT) angiography, anomalous aortic origin of a coronary artery (ANOCOR) is more frequently diagnosed. Fractional flow reserve derived from CT (FFRCT) is a noninvasive functional test providing anatomical and functional evaluation of the overall coronary tree. These unique features of anatomical and functional evaluation derived from CT could help for the management of patients with ANOCOR. We aimed to retrospectively evaluate the physiological and clinical impact of FFRCT analysis in the ANOCOR registry population. Methods and Results The ANOCOR registry included patients with ANOCOR detected during invasive coronary angiography or coronary CT angiography between January 2010 and January 2013, with a planned 5‐year follow‐up. We retrospectively performed FFRCT analysis in patients with coronary CT angiography of adequate quality. Follow‐up was performed with a clinical composite end point (cardiac death, myocardial infarction, and unplanned revascularization). We obtained successful FFRCT analyses and 5‐year clinical follow‐up in 54 patients (average age, 60±13 years). Thirty‐eight (70%) patients had conservative treatment, and 16 (30%) patients had coronary revascularization after coronary CT angiography. The presence of an ANOCOR course was associated with a moderate reduction of FFRCT value from 1.0 at the ostium to 0.90±0.10 downstream the ectopic course and 0.82±0.11 distally. No significant difference in FFRCT values was identified between at‐risk and not at‐risk ANOCOR. After a 5‐year follow‐up, only one unplanned percutaneous revascularization was reported. Conclusions The presence of ANOCOR was associated with a moderate hemodynamic decrease of FFRCT values and associated with a low risk of cardiovascular events after a 5‐year follow‐up in this middle‐aged population.

Abstract Soil microorganisms are essential to agroecosystem functioning and services. Yet, we still lack information on which farming practices can effectively shape the soil microbial communities. The aim of this study was to identify the farming practices, which are most effective at positively or negatively modifying bacterial and fungal diversity while considering the soil environmental variation at a landscape scale. A long‐term research study catchment (12 km2) representative of intensive mixed farming (livestock and crop) in Western Europe was investigated using a regular grid for soil sampling (n = 186). Farming systems on this landscape scale were described in terms of crop rotation, use of fertilizer, soil tillage, pesticides treatments, and liming. Molecular microbial biomass was estimated by soil DNA recovery. Bacterial and fungal communities were analyzed by 16S and 18S rRNA gene pyrosequencing. Microbial biomass was significantly stimulated by the presence of pasture during the crop rotation since temporary and permanent pastures, as compared to annual crops, increased the soil microbial biomass by +23% and +93% respectively. While soil properties (mainly pH) explained much of the variation in bacterial diversity, soil tillage seemed to be the most influential among the farming practices. A 2.4% increase in bacterial richness was observed along our gradient of soil tillage intensity. In contrast, farming practices were the predominant drivers of fungal diversity, which was mainly determined by the presence of pastures during the crop rotation. Compared to annual crops, temporary and permanent pastures increased soil fungal richness by +10% and +14.5%, respectively. Altogether, our landscape‐scale investigation allows the identification of farming practices that can effectively shape the soil microbial abundance and diversity, with the goal to improve agricultural soil management and soil ecological integrity.