Temporal sampling helps unravel the genetic structure of naturally occurring populations of a phytoparasitic nematode. 2. Separating the relative effects of gene flow and genetic drift

International audienceStudying wild pathogen populations in natural ecosystems offers the opportunity to better understand the evolutionary dynamics of biotic diseases in crops and to enhance pest control strategies. We used simulations and genetic markers to investigate the spatial and temporal population genetic structure of wild populations of the beet cyst nematode Heterodera schachtii on a wild host plant species, the sea beet (Beta vulgaris spp. maritima), the wild ancestor of cultivated beets. Our analysis of the variation of eight microsatellite loci across four study sites showed that (i) wild H. schachtii populations displayed fine-scaled genetic structure with no evidence of substantial levels of gene flow beyond the scale of the host plant, and comparisons with simulations indicated that (ii) genetic drift substantially affected the residual signals of isolation-by-distance processes, leading to departures from migration–drift equilibrium. In contrast to what can be suspected for (crop) field populations, this showed that wild cyst nematodes have very low dispersal capabilities and are strongly disconnected from each other. Our results provide some key elements for designing pest control strategies , such as decreasing passive dispersal events to limit the spread of virulence among field nematode populations

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Variation in neurosurgical management of traumatic brain injury: A survey in 68 centers participating in the CENTER-TBI study

Background Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Etude non invasive de la dynamique et de la génétique des populations chez une chauve-souris forestière : impact de la qualité de l'habitat et de la connectivité

Efficient conservation management against habitat degradation and fragmentation of a species requires understanding how the environment impacts its population dynamics and the species’ sensitivity to connectivity loss. Acquiring sufficient knowledge about these processes is challenging for any species, and is even more complicated for species too sensitive to be studied with classical methods. During this work, we studied the population dynamics and genetics of a woodland specialized bat who has undergone a serious decline in the north of Europe, the lesser horseshoe bat (Rhinolophus hipposideros), with non-invasive methods (counts, non-invasive genetics).Our results shown that climate and landscape around maternity colonies explain population size variations and dynamics of the lesser horseshoe bat. We also confirmed a direct impact of landscape on juvenile survival. We finally observed that genetic diversity could be strongly decreased by population history and a lack of connectivity between populations. Our results have direct implications for the lesser horseshoe bat conservation but also for the development of analyses integrating non-invasive genetic data in conservation biology.Mettre en place des mesures de protection efficaces contre la dégradation et la fragmentation de l'habitat d'une espèce nécessite d'être capable de comprendre l'impact de l'environnement sur sa dynamique de population ainsi que sa sensibilité à la perte de connectivité entre les populations. Obtenir ces informations est déjà un défi en soi, qui se complique encore pour les espèces trop sensibles au dérangement pour être suivies de manière classique. Lors de ce travail, nous avons étudié la dynamique et la génétique des populations d'une chauve-souris forestière qui a subi un très fort déclin dans le nord de l'Europe, le Petit rhinolophe (Rhinolophus hipposideros), à l'aide de méthodes non-invasives (comptages, génétique non-invasive).Nos résultats ont montré que le climat et le paysage autour des colonies de maternités influence la taille et la dynamique des populations du Petit rhinolophe. Nous avons également confirmé un impact direct du paysage sur la survie des juvéniles. Enfin, nous avons observé que la diversité génétique des populations pouvait être fortement diminuée par leurs histoires démographiques et par un manque de connectivité entre les populations. Ces résultats ont des implications directes pour la conservation du Petit rhinolophe mais aussi pour le développement des analyses intégrant des données de génétique non-invasive pour la biologie de la conservation

Non-invasive study of the population dynamics and genetics of a woodland-specialist bat : impact of habitat quality and connectivity

Mettre en place des mesures de protection efficaces contre la dégradation et la fragmentation de l'habitat d'une espèce nécessite d'être capable de comprendre l'impact de l'environnement sur sa dynamique de population ainsi que sa sensibilité à la perte de connectivité entre les populations. Obtenir ces informations est déjà un défi en soi, qui se complique encore pour les espèces trop sensibles au dérangement pour être suivies de manière classique. Lors de ce travail, nous avons étudié la dynamique et la génétique des populations d'une chauve-souris forestière qui a subi un très fort déclin dans le nord de l'Europe, le Petit rhinolophe (Rhinolophus hipposideros), à l'aide de méthodes non-invasives (comptages, génétique non-invasive).Nos résultats ont montré que le climat et le paysage autour des colonies de maternités influence la taille et la dynamique des populations du Petit rhinolophe. Nous avons également confirmé un impact direct du paysage sur la survie des juvéniles. Enfin, nous avons observé que la diversité génétique des populations pouvait être fortement diminuée par leurs histoires démographiques et par un manque de connectivité entre les populations. Ces résultats ont des implications directes pour la conservation du Petit rhinolophe mais aussi pour le développement des analyses intégrant des données de génétique non-invasive pour la biologie de la conservation.Efficient conservation management against habitat degradation and fragmentation of a species requires understanding how the environment impacts its population dynamics and the species’ sensitivity to connectivity loss. Acquiring sufficient knowledge about these processes is challenging for any species, and is even more complicated for species too sensitive to be studied with classical methods. During this work, we studied the population dynamics and genetics of a woodland specialized bat who has undergone a serious decline in the north of Europe, the lesser horseshoe bat (Rhinolophus hipposideros), with non-invasive methods (counts, non-invasive genetics).Our results shown that climate and landscape around maternity colonies explain population size variations and dynamics of the lesser horseshoe bat. We also confirmed a direct impact of landscape on juvenile survival. We finally observed that genetic diversity could be strongly decreased by population history and a lack of connectivity between populations. Our results have direct implications for the lesser horseshoe bat conservation but also for the development of analyses integrating non-invasive genetic data in conservation biology

What can be learned from wild populations of pests to better manage resistances in the fields?

Session 2: Agricultural Ecology Pests and PesticidesFollowing the ban of pesticide treatments, resistant varieties have emerged as one of the best environmental-friendly methods to control populations of parasitic nematodes. However, as host resistances exert strong selective pressures on parasites populations, they are likely to be overcome more or less rapidly, according to the effective sizes of parasite populations and to the level of gene flow among them. In agricultural landscapes, gene flow is mainly the result of human activities. Hence, to better manage these pests in agricultural fields, these two parameters should be evaluated in non-disturbed wild populations. The cyst nematode Heterodera schachtii is growing both on cultivated beet, in the fields, and on its wild relative, the sea beet. To characterize effective sizes and levels of gene flow in the wild, we assessed the temporal variation of allele frequencies at microsatellite loci from two successive samples taken one year apart on individual plants from different beaches. According to the environmental conditions of the studied areas, the number of generations produced by Heterodera schachtii between the two samplings was estimated as ranging from 4 to 10. Patterns of genetic diversity observed were incompatible with the occurrence of efficient gene flow, even between neighboring host plants, which resulted in low effective population sizes with respect to the actual number of individuals found in each rhizosphere of host plants. These low effective population sizes and the inability of the parasite to actively disperse over large distances suggested very limited possibilities to overcome resistances, provided that the passive transport of cysts by agricultural machinery, and by spreading sludge processing from sugar factories, are themselves limited

Exploring the causes of small effective population sizes in cyst nematodes using artificial Globodera pallida populations

International audienceThe effective size of a population is the size of an ideal population which would undergo genetic drift at the same rate as the real population. The balance between selection and genetic drift depends on the effective population size (N-e), rather than the real numbers of individuals in the population (N). The objectives of the present study were to estimate N-e in the potato cyst nematode Globodera pallida and to explore the causes of a low N-e/N ratio in cyst nematodes using artificial populations. Using a temporal analysis of 24 independent populations, the median N-e was 58 individuals (min N-e = 25 and max N-e = 228). N-e is commonly lower than N but in the case of cyst nematodes, the N-e/N ratio was extremely low. Using artificial populations showed that this low ratio did not result from migration, selection and overlapping generations, but could be explain by the fact that G. pallida populations deviate in structure from the assumptions of the ideal population by having unequal sex ratios, high levels of inbreeding and a high variance in family sizes. The consequences of a low N-e, resulting in a strong intensity of genetic drift, could be important for their control because G. pallida populations will have a low capacity to adapt to changing environments