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It is crucial that biodiversity conservation initiatives in agriculture take into account how farmers understand and value their relationships with nature. However, while highly relevant for pan‐European conservation work, insight into differences and commonalities in farmers' views across socio‐ecologically different European regions is still lacking. Therefore, we studied how farmers describe the relationship between how they farm and biodiversity in two contrasting regions: the Netherlands and the French Massif Central. In both regions, we included two specific study areas. We focused on dairy farming, as it is a key sector in terms of socio‐economic importance and biodiversity impact in both regions. In each area, we conducted 15 in‐depth interviews focusing on the impacts of the farm on biodiversity and vice versa, as well as on the relational importance of biodiversity to the farmer. We allowed farmers to use the term ‘biodiversity’ in their own words. We analysed our data using the Integrated Nature Futures Framework (I‐NFF), a recently proposed framework for analysing what people value positively and negatively about nature‐related matters. Six main narratives emerged, which we named ‘farming WITH biodiversity’, ‘farming FROM biodiversity—valorising what is there’, ‘farming FROM biodiversity—innovating for sustainability’, ‘farming FOR biodiversity’, ‘farming SEPARATE from biodiversity—out of necessity’ and ‘farming SEPARATE from biodiversity—out of conviction’. These narratives vary in how farmers conceptualise biodiversity, perceive and value interactions between farming and biodiversity, and define problems and solutions. Although we encountered partly the same narratives in the Dutch and Massif Central areas, we also noted considerable differences. In the Dutch areas, we frequently encountered ‘FOR’, which strongly depicts biodiversity as an additional service that requires payment, and ‘SEPARATE—out of conviction’, which argues for production‐intensive systems. In the Massif Central areas, we virtually never encountered these narratives and instead more often encountered ‘WITH’, which depicts farming as naturally integrated with biodiversity. Moreover, the narratives had strong region‐specific details. We close by discussing how better insight into such differences and commonalities can help foster more understanding engagement with farmers on the topic of biodiversity. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog.

The analysis of the consequences of participatory foresight in agriculture over the long term is little studied in the scientific literature. In particular, it questions how farmers deal with the proposed scenarios afterwards and the modalities of their implementation. This article aims to overcome this by proposing an ex-post analysis of a foresight process with New World Kirkpatrick's Model (NWKM) carried out in mid-2018 in the Fourme de Montbrison cheese Protected Designation of Origin (PDO) area in the Massif Central (France). A set of 24 semi-structured interviews was conducted in spring and summer 2020 with the dairy farmers involved. Moreover, collective organization has been investigated through participatory observation and an analysis of project's progress reports until March 2021. The results show that while the engagement of farmers in the collective dynamic remains, it needs to be continuously rebuilt over time, particularly in order to overcome the effects of social risk-taking and insecurity that farmers must face. In addition, the place of stakeholders needs to be clarified. The article proposes a series of guidelines based on the project's experience and the “Monitor and Adjust” approach of the NWKM. It demonstrates the importance of establishing long-term follow-ups to foresight approaches to encourage farmers into action.

This article offers a method for the ongoing evaluation of an approach to support farmers, based on a combination of serious games. This approach was proposed to a group of farmers in a French cheese PDO area producing the Fourme de Montbrison, to adapt their fodder management practices to climate change. Four games (Lauracle, Rami fourrager, Aeole, Dynamix) were combined on different scales (farm, territory) with other forms of animation (training, on-farm experimentation, farm visits) for two years. The Kirkpatrick’s evaluation model was adapted and used to assess this approach on four levels of evaluation (reactions, learning, behaviour and results). We use a combination of different tools before, during and after game sessions such as participant observation; in-game observations and debriefings of game sessions; interviews and technical diagnosis. Several monitoring and adjustment sequences during the design of the process are highlighted allowing to improve its adequacy and applicability. The adjustments concern the choice of the games, their animation, and the support process on the field. They highlight the importance of integrating the evaluation along the way to design and improve a support process based on serious games. The perspective of this work is to evaluate the effects of the whole approach, by identifying effective changes in perceptions and practices, and to make this theoretical model operational for agricultural extension.

The analysis of the consequences of participatory foresight in agriculture over the long term is little studied in the scientific literature. In particular, it questions how farmers deal with the proposed scenarios afterwards and the modalities of their implementation. This article aims to overcome this by proposing an ex-post analysis of a foresight process with Kirkpatrick’s model carried out in mid-2018 in a PDO territory in the Massif Central (France). A set of 24 semi-structured interviews was conducted in spring and summer 2020 with the dairy farmers involved. Moreover, collective organization has been investigated through participatory observation and an analysis of project's progress reports until March 2021. The results show that while the engagement of farmers in the collective dynamic remains, it needs to be continuously rebuilt over time, particularly in order to overcome the effects of social risk-taking that farmers must face. The article proposes a series of guidelines based on the project's experience and demonstrates the importance of establishing long-term follow-ups of foresight approaches to encourage farmers into action.

Despite recent improvements in sequencing methods, there remains a need for assays that provide high sequencing depth and comprehensive variant detection. Current methods 1 – 4 are limited by the loss of native modifications, short read length, high input requirements, low yield or long protocols. In the present study, we describe nanopore Cas9-targeted sequencing (nCATS), an enrichment strategy that uses targeted cleavage of chromosomal DNA with Cas9 to ligate adapters for nanopore sequencing. We show that nCATS can simultaneously assess haplotype-resolved single-nucleotide variants, structural variations and CpG methylation. We apply nCATS to four cell lines, to a cell-line-derived xenograft, and to normal and paired tumor/normal primary human breast tissue. Median sequencing coverage was 675× using a MinION flow cell and 34× using the smaller Flongle flow cell. The nCATS sequencing requires only ~3 μg of genomic DNA and can target a large number of loci in a single reaction. The method will facilitate the use of long-read sequencing in research and in the clinic. Point mutations, structural variants and DNA methylation at target loci are assessed by nanopore sequencing.

Defects in endosomal sorting have been implicated in Alzheimer’s disease. Endosomal traffic is largely controlled by phosphatidylinositol-3-phosphate, a phosphoinositide synthesized primarily by lipid kinase Vps34. Here we show that phosphatidylinositol-3-phosphate is selectively deficient in brain tissue from humans with Alzheimer’s disease and Alzheimer’s disease mouse models. Silencing Vps34 causes an enlargement of neuronal endosomes, enhances the amyloidogenic processing of amyloid precursor protein in these organelles and reduces amyloid precursor protein sorting to intraluminal vesicles. This trafficking phenotype is recapitulated by silencing components of the ESCRT (Endosomal Sorting Complex Required for Transport) pathway, including the phosphatidylinositol-3-phosphate effector Hrs and Tsg101. Amyloid precursor protein is ubiquitinated, and interfering with this process by targeted mutagenesis alters sorting of amyloid precursor protein to the intraluminal vesicles of endosomes and enhances amyloid-beta peptide generation. In addition to establishing phosphatidylinositol-3-phosphate deficiency as a contributing factor in Alzheimer’s disease, these results clarify the mechanisms of amyloid precursor protein trafficking through the endosomal system in normal and pathological states. Endosomal sorting is regulated by phosphatidylinositol-3-phosphate and anomalies in this process are implicated in Alzheimer’s disease. Here the authors show that deficiency of phosphatidylinositol-3-phosphate in vitro enhances the pathological trafficking and processing of amyloid precursor protein.

The recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only WHO prequalified vaccine recommended for use to respond to outbreaks of Ebola virus (species Zaire ebolavirus) by WHO's Strategic Advisory Group of Experts on Immunization. Despite the vaccine's widespread use during several outbreaks, no real-world effectiveness estimates are currently available in the literature. We conducted a retrospective test-negative analysis to estimate effectiveness of rVSV-ZEBOV vaccination against Ebola virus disease during the 2018–20 epidemic in the Democratic Republic of the Congo, using data on suspected Ebola virus disease cases collected from Ebola treatment centres. Those eligible for inclusion had an available Ebola virus RT-PCR result, available key data, were eligible for vaccination during the outbreak, and had symptom onset aligning with the period in which a ring-vaccination protocol was in use. After imputing missing data, each individual confirmed by RT-PCR to be Ebola virus disease-positive (defined as a case) was matched to one individual negative for Ebola virus disease (control) by sex, age, health zone, and month of symptom onset. Effectiveness was estimated from the odds ratio of being vaccinated (≥10 days before symptom onset) versus being unvaccinated among cases and controls, after adjusting for the matching factors. The imputation, matching and effectiveness estimation, was repeated 500 times. 1273 (4·8%) of 26 438 eligible individuals were positive for Ebola virus disease (cases) and 25 165 (95·2%) were negative (controls). 40 (3·1%) cases and 1271 (5·1%) controls were reported as being vaccinated at least 10 days before symptom onset. After selecting individuals who reported exposure to an individual with Ebola virus disease within the 21 days before symptom onset and matching, the analysis datasets comprised a median of 309 cases and 309 controls. 10 days or more after vaccination, the effectiveness of rVSV-ZEBOV against Ebola virus disease was estimated to be 84% (95% credible interval 70–92). This analysis is the first to provide estimates of the real-world effectiveness of the rVSV-ZEBOV vaccine against Ebola virus disease, amid the widespread use of the vaccine during a large Ebola virus disease outbreak. Our findings confirm that rVSV-ZEBOV is highly protective against Ebola virus disease and support its use during outbreaks, even in challenging contexts such as in the eastern Democratic Republic of the Congo. Médecins Sans Frontières. For the French translation of the abstract see Supplementary Materials section.

Purpose To examine whether increased lateral femoral condyle ratio (LFCR) correlates with increased risk of Anterior cruciate ligament (ACL) injury (1) and to evaluate the relationship between the LFCR and anterolateral complex (ALC) injury in non-contact ACL torn knees (2). Methods Six hundred and seventy-two patients who underwent ACL reconstruction surgery between 2013 and 2019 were retrospectively reviewed, and 120 patients were finally included in the study. Forty patients (ACL + ALC injury) were included in the study group, while forty patients with isolated ACL injury (isolated ACL injury group) and 40 patients who suffered from meniscal tear without ACL or ALC injury were matched in a 1:1 fashion by age, sex, and BMI to the study group (ACL + ALC injury). The LFCR was measured on standard lateral radiographs in a blinded fashion. The differences between the three groups were analyzed by ANOVA. A ROC (Receiver Operating Characteristic) curve was produced to determine risk of ACL injury and risk of concomitant ALC injury in non-contact ACL injury. Results The mean LFCR was 71.9% ± 3.1% in the ACL + ALC injury group, 68.4% ± 3.2% in the isolated ACL injury group, and 66.8% ± 2.6% in the control group (patients who suffered from meniscal tear without ACL or ALC injury). Significantly greater LFCR was found in the ACL + ALC injury group than that in the isolated ACL injury group ( p  < 0.017). Greater LFCR was additionally confirmed in the ACL injury group as compared to the control group ( p  < 0.05). ROC curve analysis demonstrated that LFCR > 68.3% was predictive for an increased risk of ACL injury in the entire cohort. LFCR > 69.4% was predictive for an increased risk of ALC injury in non-contact ACL ruptured patients. Conclusion Increased LFCR was found to be associated with greater risk of ALC injury in non-contact ACL ruptured patients. Additionally, increased LFCR was further confirmed to be correlated with increased risk of ACL injury in an Asian population. The data from this study may help recognize patients undergoing ACL reconstruction that could benefit from additional extra-articular tenodesis. Level of evidence III.

The rVSVΔG-ZEBOV-GP vaccine constitutes a valuable tool to control Ebola virus disease outbreaks. This retrospective cohort study aimed to assess the protective effect of the vaccine against death among patients with confirmed Ebola virus disease. In this retrospective cohort analysis of patients with confirmed Ebola virus disease admitted to Ebola health facilities in the Democratic Republic of the Congo between July 27, 2018, and April 27, 2020, we performed univariate and multivariate analyses to assess case fatality risk and cycle threshold for nucleoprotein according to vaccination status, Ebola virus disease-specific treatments (eg, mAb114 and REGN-EB3), and other risk factors. We analysed all 2279 patients with confirmed Ebola virus disease. Of these 2279 patients, 1300 (57%) were female and 979 (43%) were male. Vaccination significantly lowered case fatality risk (vaccinated: 25% [106/423] vs not vaccinated: 56% [570/1015]; p<0·0001). In adjusted analyses, vaccination significantly lowered the risk of death compared with no vaccination, with protection increasing as time elapsed from vaccination to symptom onset (vaccinated ≤2 days before onset: 27% [27/99], adjusted relative risk 0·56 [95% CI 0·36–0·82, p=0·0046]; 3–9 days before onset: 20% [28/139], 0·44 [0·29–0·65, p=0·0001]; ≥10 days before onset: 18% [12/68], 0·40 [0·21–0·69; p=0·0022]; vaccination date unknown: 33% [39/117], 0·69 [0·48–0·96; p=0·0341]; and vaccination status unknown: 52% [441/841], 0·80 [0·70–0·91, p=0·0011]). Longer time from symptom onset to admission significantly increased risk of death (49% [1117/2279], 1·03 [1·02–1·05; p<0·0001]). Cycle threshold values for nucleoprotein were significantly higher—indicating lower viraemia—among patients who were vaccinated compared with those who were not vaccinated; the highest difference was observed among those vaccinated 21 days or longer before symptom onset (median 30·0 cycles [IQR 24·6–33·7]) compared with patients who were not vaccinated (21·4 cycles [18·4–25·9], p<0·0001). To our knowledge, this is the first observational study describing the protective effect of rVSVΔG-ZEBOV-GP vaccination against death among patients with confirmed Ebola virus disease admitted to an Ebola health facility. Vaccination was protective against death for all patients, even when adjusted for Ebola virus disease-specific treatment, age group, and time from symptom onset to admission. Médecins Sans Frontières. For the French translation of the abstract see Supplementary Materials section.

Bantu languages are spoken by about 310 million Africans, yet the genetic history of Bantu-speaking populations remains largely unexplored. We generated genomic data for 1318 individuals from 35 populations in western central Africa, where Bantu languages originated. We found that early Bantu speakers first moved southward, through the equatorial rainforest, before spreading toward eastern and southern Africa. We also found that genetic adaptation of Bantu speakers was facilitated by admixture with local populations, particularly for the HLA and LCT loci. Finally, we identified a major contribution of western central African Bantu speakers to the ancestry of African Americans, whose genomes present no strong signals of natural selection. Together, these results highlight the contribution of Bantu-speaking peoples to the complex genetic history of Africans and African Americans.