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This paper explores transnational circulation during the early 1970s of lifelong education and recurrent education as 'policy repertoires' addressing redistribution of participation in organised (adult) learning throughout life. Focused on a re-reading of UNESCO's 1972 report on lifelong education, the paper offers a critical analysis of the Faure Commission's 'position-taking' with regard to its understanding of recurrent education as a policy repertoire. Frequently cited differences between the Commission's policy recommendations for lifelong education and its position-taking regarding recurrent education are shown to have fragile empirical foundations. This paper argues that Faure's report explicitly appropriated and openly incorporated arguments favouring recurrent education in its own policy recommendations for lifelong education. Mainstream interpretations of the Faure report are subsequently subjected to a critical analysis of putative neoliberal tendencies articulated by the Faure Commission's own report. Key areas for further social-historical research regarding policy repertoires in the 1970s are identified.

UNLABELLED: As the closest living relatives of animals, choanoflagellates offer insights into the ancestry of animal cell physiology. Here, we report the isolation and characterization of a colonial choanoflagellate from Mono Lake, California. The choanoflagellate forms large spherical colonies that are an order of magnitude larger than those formed by the closely related choanoflagellate Salpingoeca rosetta. In cultures maintained in the laboratory, the lumen of the spherical colony is filled with a branched network of extracellular matrix and colonized by bacteria, including diverse Gammaproteobacteria and Alphaproteobacteria. We propose to erect Barroeca monosierra gen. nov., sp. nov. Hake, Burkhardt, Richter, and King to accommodate this extremophile choanoflagellate. The physical association between bacteria and B. monosierra in culture presents a new experimental model for investigating interactions among bacteria and eukaryotes. Future work will investigate the nature of these interactions in wild populations and the mechanisms underpinning the colonization of B. monosierra spheres by bacteria. IMPORTANCE: The diversity of organisms that live in the extreme environment of Mono Lake (California, USA) is limited. We sought to investigate whether the closest living relatives of animals, the choanoflagellates, exist in Mono Lake, a hypersaline, alkaline, arsenic-rich environment. We repeatedly isolated members of a new species of choanoflagellate, which we have named Barroeca monosierra. Characterization of B. monosierra revealed that it forms large spherical colonies containing diverse co-isolated bacteria, providing an opportunity to investigate mechanisms underlying physical associations between eukaryotes and bacteria.

BackgroundPosterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort.MethodsWe searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2.FindingsWe identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9-59·8; I2=77%), 60% (56-64; I2=35%) were women, and 80% (72-89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid β in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75-87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56-75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90-97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93-100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90-97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54-88; I2=89%), Lewy body disease (44%, 25-62; I2=77%), and cerebrovascular injury (42%, 24-60; I2=88%).InterpretationThese data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity.FundingNone.

To fully understand human memory, it is necessary to understand its lifespan development. However, memory assessments often rely on significantly different methodologies for different age groups, and their results are typically not directly comparable. In this paper, we present a quantitative assessment of memory function spanning an age range of five to 85 years that is based on a model-based memory assessment. This approach yields a uniform metric that is directly interpretable and can be compared across different tasks and materials that are appropriate for different age groups. The results show a robust U-shape function, with long-term memory function at age 5 being comparable to that of cognitively impaired elderly individuals. These results and the method utilized could provide a new foundation for future studies on memory development across life stages.

Expanding on previous research highlighting the learning benefits of errors, this study explores the enduring effects of error-induced learning. Using an adaptive fact-learning system, 23 participants engaged in recognition, recall, and error tasks, with repeated testing for memory assessment. Initial findings echoed previous results: items learned through errors initially took longer to retrieve. However, a significant shift occurred over time; error items demonstrated faster retrieval speeds compared to study items, and, most notably, they exhibited greater resilience against forgetting. This study reaffirms the positive role of errors in learning and uncovers their contribution to enhanced long-term memory retention. These insights challenge traditional learning paradigms, advocating for an educational approach that recognizes and leverages the value of errors in learning processes.

BackgroundThe distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.MethodsData for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong).ResultsNo histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis.ConclusionsWe provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.

Recent studies suggest that errors facilitate learning in certain conditions. Despite this, reinforcement paradigms dominate learning methods, subscribing to the narrative that errorless learning is the foundation of an ideal learning environment. If we continue to view learning from this restrictive perspective, we may fail to capture and apply the benefits of errors. In this paper, we investigate two potential mechanisms of post-error learning. Participants (N = 61) learned word pairs in either a study or error trial before taking a final test. Supporting past error learning literature, errors before a study opportunity led to better performance on a final test. Differences in reaction times between conditions support the theory that errors increase learning by acting as a mediator, or secondary cue, to the correct answer on subsequent tests.

Computational models of memory used in adaptive learning settings trace a learner's memory capacities. However, less work has been done on the implementation of these models in the clinical realm. Current assessment tools lack the reliable, convenient, and repeatable qualities needed to capture the individualized and evolving nature of memory decline. The goal of this project was to predict and track memory decline in subjectively- or mildly cognitively impaired (MCI) individuals by using a model-based, adaptive fact-learning system. Here, we present data demonstrating that these tools can diagnose mild memory impairment with over 80% accuracy after a single 8-minute learning session. These findings provide new insights into the nature and progression of memory decline and may have implications for the early detection and management of Alzheimer's disease and other forms of dementia.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.

PurposeTo evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.MethodsWe included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk.ResultsFor BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC

Plant meristems are self-renewing groups of pluripotent stem cells that produce lateral organs in a stereotypical pattern. Of interest is how the radially symmetrical meristem produces laminar lateral organs. Both the male and female inflorescence meristems of the dominant Fascicled ear (Fas1) mutant fail to grow as a single point and instead show deep branching. Positional cloning of two independent Fas1 alleles identified an ∼160 kb region containing two floral genes, the MADS-box gene, zmm8, and the YABBY gene, drooping leaf2 (drl2). Both genes are duplicated within the Fas1 locus and spatiotemporally misexpressed in the mutant inflorescence meristems. Increased zmm8 expression alone does not affect inflorescence development; however, combined misexpression of zmm8, drl2, and their syntenic paralogs zmm14 and drl1, perturbs meristem organization. We hypothesize that misexpression of the floral genes in the inflorescence and their potential interaction cause ectopic activation of a laminar program, thereby disrupting signaling necessary for maintenance of radially symmetrical inflorescence meristems. Consistent with this hypothesis, RNA sequencing and in situ analysis reveal altered expression patterns of genes that define distinct zones of the meristem and developing leaf. Our findings highlight the importance of strict spatiotemporal patterns of expression for both zmm8 and drl2 and provide an example of phenotypes arising from tandem gene duplications.

The basal ganglia (BG) performs an important functional role in cognition, but models disagree about the nature of the relationship between BG activity and activity in other cortical areas. Previous computational models can be categorized as implementing the effects of the BG on prefrontal cortex as either local and direct, or involving other regions and, therefore, modulatory. To test which of these two effects best represents the role of the BG, a large fMRI dataset of 200 participants performing six, representative cognitive tasks was analyzed through Dynamic Causal Modeling (DCM). To ensure that DCM models were realistic and representative of a general brain architecture, the models were implemented within the putative neural underpinnings of the Common Model of Cognition, an abstract blueprint for cognition. The comparison showed that Mixed model, including both Direct and Modulatory connectivity, consistently outperformed models that included only direct or modulatory connections. It was also found that the relative rankings of the Direct and Modulatory models depended on the specific task, suggesting that the BG is a flexible system that adapts to task demands.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P

This paper examines transnational circulation of political and pedagogical ideas associated with "éducation permanente" with particular reference to post-war Western Europe. It offers a socio-historical reconstruction of pan-European dissemination and reception of policy repertoires articulated by governmental and non-governmental policy actors. It focuses on advocacy regarding permanent education as a pan-European repertoire associated with the Council of Europe during the 1960s and 1970s. The paper explores involvement of French and other francophone nationals in circulatory regimes, who were engaged in mediating partisan reform aspirations, exchange of information, and dissemination of innovative practices at national, transnational, and pan-European levels. The more specific focus of this paper addresses participation of 'rooted cosmopolitans' in policy formation, who are defined as policy actors rooted in specific national contexts, but who engage in regular activities involving their participation in transnational networks. The conclusions call for further research into circulatory regimes at local, sub-national, regional, national, bilateral, transnational, and pan-European during the 1960s and 1970s. Such research should focus on revisiting different expert, reformist, missionary, and militant networks responsible for building peripatetic 'scholar-militant-activist' coalitions that historically contributed to pan-European policy repertoires seeking to mobilise citizens to participate in the unfinished political project of pan-European cultural democracy.

The literature regarding the social organisation of 'adult' learning opportunities throughout the life course postulates different significations of policy concepts such as 'lifelong education', 'permanent education', 'recurrent education', and 'lifelong learning' in the 1970s. This paper examines policy formation processes in France during the 1950s when the development of "éducation permanente" was characterised by often-conflicting policy repertoires articulating arguments for redistributing opportunities to participate in organised (adult) learning throughout life. In the post-war context of rapid economic growth and technological change, it focuses on the policy repertoires articulated by the state, civil society organisations, and markets regarding individual and collective opportunities to continue to acquire knowledge, skills and sensitivities throughout life. Based upon a critical rereading of primary and secondary published texts, the analysis suggests that "éducation permanente" constituted a social field of problematic relationships between individual and collective interests regarding the acquisition of knowledge, skills and sensitivities. This constituted the dialectic between economic/vocational, technical reconversion practices in relation to social, cultural, and personal regeneration practices in a rapidly changing capitalist society. The conclusions identify a number of issues calling for further comparative historical research into often-conflicting policy repertoires that propagated policies to promote 'long lives of learning'.

Limited access to healthy food caused by food insecurity makes diabetes mellitus (DM) self-management more challenging. Using data from Hunger in America 2014 (n = 60,122 US food pantry users), we sought to understand food preferences and coping strategy utilization (e.g. choosing between paying for food and medical care) among households seeking assistance from US food pantries with and without DM members. The prevalence of wanting and not obtaining fruits, vegetables, dairy, and protein was high among all households. After adjusting for sociodemographic characteristics, households with DM members were more likely to want and not obtain fruits, vegetables, and dairy, and were also more likely to use several coping strategies to increase food access, compared to households without DM members. These results highlight the high demand for healthy food items among clients from US food pantries, particularly among households with DM, as well as the extra burden DM may place on food insecure households.

Delineation between distinct populations of cells is essential for organ development. Boundary formation is necessary for the maintenance of pluripotent meristematic cells in the shoot apical meristem (SAM) and differentiation of developing organs. Boundaries form between the meristem and organs, as well as between organs and within organs. Much of the research into the boundary gene regulatory network (GRN) has been carried out in the eudicot model Arabidopsis thaliana. This work has identified a dynamic network of hormone and gene interactions. Comparisons with other eudicot models, like tomato and pea, have shown key conserved nodes in the GRN and species-specific alterations, including the recruitment of the boundary GRN in leaf margin development. How boundaries are defined in monocots, and in particular the grass family which contains many of the world's staple food crops, is not clear. In this study, we review knowledge of the grass boundary GRN during vegetative development. We particularly focus on the development of a grass-specific within-organ boundary, the ligule, which directly impacts leaf architecture. We also consider how genome engineering and the use of natural diversity could be leveraged to influence key agronomic traits relative to leaf and plant architecture in the future, which is guided by knowledge of boundary GRNs.

Alzheimer's disease (AD) is a leading cause of mortality among the elderly. We performed a whole-genome sequencing study of AD in the Chinese population. In addition to the variants identified in or around the APOE locus (sentinel variant rs73052335, P = 1.44 × 10-14), two common variants, GCH1 (rs72713460, P = 4.36 × 10-5) and KCNJ15 (rs928771, P = 3.60 × 10-6), were identified and further verified for their possible risk effects for AD in three small non-Asian AD cohorts. Genotype-phenotype analysis showed that KCNJ15 variant rs928771 affects the onset age of AD, with earlier disease onset in minor allele carriers. In addition, altered expression level of the KCNJ15 transcript can be observed in the blood of AD subjects. Moreover, the risk variants of GCH1 and KCNJ15 are associated with changes in their transcript levels in specific tissues, as well as changes of plasma biomarkers levels in AD subjects. Importantly, network analysis of hippocampus and blood transcriptome datasets suggests that the risk variants in the APOE, GCH1, and KCNJ15 loci might exert their functions through their regulatory effects on immune-related pathways. Taking these data together, we identified common variants of GCH1 and KCNJ15 in the Chinese population that contribute to AD risk. These variants may exert their functional effects through the immune system.