dataesr/scientific-paragraphs-categorization huggingface dataset:
Fourth, we tested associations between specific negative childhood events and participants' internalizing symptoms trajectories adjusting for covariates. In additional analyses, we tested interactions between negative events and participants' sex and age. Moreover, restricting the sample to participants with complete 1991, 1999, and 2009 data (n5674), we tested whether the association between negative childhood events and internalizing symptoms trajectories was not explained by high childhood emotionality. Analyses were performed using SPSS (version 16. 0, SPSS Inc, Chicago, ILL) and SAS V9 (SAS Institute, 2006).
Schmahmann. Dr. Habas then provides an evaluation of the functional connections between the cerebellum and cerebral perceptual systems, drawing on studies using modern neuroimaging techniques. Dr. Paulin provides an evolutionary and comparative perspective on cerebellar involvement in perceptual functions. Evidence for a cerebellar role in visual and auditory processing is summarized by Drs. Baumann and Mattingley, followed by a commentary from Drs. Pavlova and Sokolov on visual processing of biological motion. Dr. Cullen writes on the critical function of the cerebellum in self-motion perception. Evidence for a role of the cerebellum in pain perception is reviewed by Drs. Borra and Moulton. Dr. Ivry presents a hypothesis and data to suggest that the cerebellum acts as a timing device for motor and nonmotor processes.
Acknowledgments (1)  Dr. Schmahmann 's work was supported in part the  MINDlink and Birmingham Foundations. (2) Dr. Baumann was supported by an  Australian Research Council (ARC)   Discovery Early Career Researcher Award  and  Dr. Mattingley  by an  ARC   Australian Laureate Fellowship  ( FL110100103 ), the  ARC-SRI Science of Learning Research Centre  ( SR120300015 ), and the  ARC Centre of Excellence for Integrative Brain Function  ( ARC Centre Grant   CE140100007 ). (3)  Dr. Pavlova  was supported by  Else Kröner Fresenius Foundation  (Grant  P2013_127 ), the  Reinhold-Beitlich Foundation , the  Berthold Leibinger Foundation , and the  Heidehof Foundation  (Grant  59073. 01. 1/3. 13 ). (4)  Dr. Borra  was supported by funding from the  Sigrid Juselius Foundation , the  Instrumentarium Research Foundation , the  Finnish Medical Foundation , the  Paulo Foundation  and the  Academy of Finland  ( 270352 ).
In Budongo, unlike Taı ¨, chimpanzees are not exposed to significant predation pressure (no confirmed sightings of large predators such as leopards since the onset of long-term research in 1992 and no direct human hunting of primates  [15] ), nor have there been any confirmed cases of death from anthropogenic disease  [15]. Chimpanzee deaths as a result of human-wildlife conflict over crop-raiding have been recorded, as have deaths from snaretraps laid with the intention of catching other prey, such as antelope or bush-pigs, but in general, mortality rates in this community are relatively low. Because these low mortality rates impact on the number of orphans, and therefore on the number of opportunities for adoption available for analysis, we combined the new data from our own long-term records with those extracted from the published records of two other longterm East African chimpanzee research sites, Gombe and Mahale, in which no systematic analysis of adoption has taken place.
Data collection Since the onset of research at the Budongo Conservation Field Station in 1991  [15] , field assistants have been recording party composition, ranging behaviour, and the frequency and duration of key social behaviours between individuals, such as grooming and aggression. Cases of adoption and associated behaviour in the Sonso chimpanzee community were extracted from long-term data sources. Researchers and field assistants keep a logbook for the purpose of collating unusual or rare observations; this record includes all deaths and adoptions between 1991 and 2013, and more detailed reports of allomaternal care provided to orphaned infants between October 2007 and January 2013. In addition, we interrogated the six highly experienced chimpanzee field assistants, two of whom have worked with the Sonso community for over 20 years.
Briefly, we noninvasively collected chimpanzee faecal samples, which were first processed with a two-step ethanol-silica method, before extracting DNA using the QIAamp DNA stool kit with slight modifications of the manufacturer's (QIAGEN) protocol  [24]. We then used a two-step amplification method, where we initially combined all primer pairs with template DNA in a multiplex PCR followed by dilutions of the resultant PCR products for amplification of each individual locus, using fluorescently labelled forward primers and nested reverse primers in singleplex PCR reactions  [25]. Paternity was assigned through likelihood-based methods implemented in the program CERVUS  [26]  and for male offspring, through Y-chromosome haplotype sharing. CERVUS analyses were conducted with the following parameters: 10,000 simulated offspring, 0.
Analysis of published data from other long-term field sites Cases of orphaned individuals reported at other sites were examined for the following details: age of orphan, presence of maternal sibling in community, age of adopter (in years), any known kin-relationship of adopter to orphan, time before care was provided (in months), and survival of orphan after one year. Where data were unavailable these cases were excluded from the relevant analyses. In cases where the adoption or care was described simply as 'fast' or 'quick', we assigned an estimate of 1week. In a small number of cases in the Taı ¨communities (where mortality is high), single individuals adopted more than one orphan, although this never occurred simultaneously. In one case an individual could have contributed more than one data point to an analysis, in this case we calculated and used a single mean value.
463. 8 years; unpaired t-test: t = 4. 76 df = 24 p,0. 0001). Given the effectiveness of adoption by both mature individuals and immature siblings, we analysed all cases of adoptions across the different field sites for the presence or absence of kin members in the group at the time of adoption. Importantly, we found that in none of the 16 cases in which an orphan had an older maternal sibling present was it adopted by an unrelated individual, even when the only older maternal sibling present was also an immature individual (which occurred in 11/16 cases). Our own data and the data of all long-term sites thus show that orphaned infant chimpanzees are first and foremost adopted by maternal siblings, regardless of age, if they are available. Where maternal siblings are not available, unrelated mature individuals may then adopt.
Discussion Our study shows that, across the major East African chimpanzee study sites, kin adoption takes priority, even if the kin-adopters are themselves still immature and mature non-kin adopters are available, suggesting that the 'default' pattern of adoption in chimpanzees is based on mutual support between orphaned siblings. Adoption by unrelated mature individuals does happen, and indeed was the most frequently observed type of adoption in the total data set and for the Tai community. Importantly, Table  1. Individuals recorded as adopting (providing allomaternal-care to) orphans at long-term chimpanzee research sites, including cases of temporary care given during mother's absence. The adopter's age is given in years at time of the mother's death or disappearance. Time to start of care is recorded in months (note cases recorded as 'fast' are listed as 1-week or less).
Despite ample cases of sibling adoption we found no evidence for adoption by a paternal sibling (see Table  S1 ), suggesting that the social-bonds that exist before the death of their mother play a key factor in the onset of adoptive behaviour. This hypothesis is further supported by the interesting exception to maternal sibling adoption in the Sonso community, where the orphan 'Polina' was not adopted by her maternal brother 'Pascal'. The two siblings were separated by an unusually long interbirth interval of six years, and at the time of their mother's death 'Pascal' had already been associating with the adult males of the community for several years, and only infrequently spent time with his mother and 'Polina'. We observed only one case of non-kin adoption in Sonso, although non-kin adoptions formed the majority of cases in the dataset.
Acknowledgments We thank the staff of the  Budongo Conservation Field Station , the  Uganda National Council for Science and Technology , the  President's Office , the  Uganda Wildlife Authority  and the National Forestry Authority. We thank two reviewers for their helpful comments. We thank  C. Rowney  for assistance with laboratory analyses and  C. Crockford ,  R. Wittig ,  V. Reynolds ,  Z. Zommers  and  L. Vigilant  for providing faecal samples.
This research was funded by the  Leverhulme Trust   Research Leadership Award F/00268/AP  (http://www. leverhulme. ac. uk/), a  Wenner-Gren Foundation Dissertation Fieldwork  grant (http://www. wennergren. org/),the  British Academy  Grant  SG411998  (http://www. brit. ac. uk) and the  Royal Zoological Society of Scotland  (http://www. rzss. org. uk). This project has received funding from the  European Union 's  Seventh Framework Programme  for research, technological development and demonstration under grant agreement no. 283871. Genetic analyses were funded by the  Max Planck Society, Boston University , and the  Leakey Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Statistical analysis was performed by the RKward V 0. 6. 1 software with 0. 05 denoting significance. The study was performed and presented in accordance with the STROBE guidelines. A thematic analysis of the advance directives was performed by two researchers. Results: A total of 197 medical records were evaluable. The mean age of the patients was 66 years (range: 18-91). Nearly 2/3 of them (64. 5%) designated a proxy, 6. 1% wrote advance directives, and 8. 1% and 4. 6% expressed a wish to meet a religious representative or a volunteer, respectively. The 2-year survival rate was 78. 4% [95%CI: 68. 2-90. 2]. Patients who wrote advance directives were statistically older (p <0. 00025). Patients who wrote an advance directive were more likely to have expressed a wish to meet a religious representative (p <0.
Sample selection Two hundred medical records of patients presenting with an HM and treated in the Haematological Unit of a University Hospital (Limoges, France) from June 1, 2008 to April 30, 2012 were randomly drawn. Data was extracted by a clinical research engineer using an abstraction protocol to perform a retrospective descriptive quantitative analysis  [17]. Demographic and study data were collected from the patient information form which is completed by all patients on their first visit to the centre and kept in their medical records. Any medical records without this patient information form filled in by the patient or his legal representative were not retained for analysis. Study data included: whether an HCP had been designated, whether an AD had been written and was available, mention of a wish to meet a religious representative or a volunteer.
Demographic data A total of 2180 medical records were listed during the study period. Among them, 200 were randomly selected and 197 (98. 5%) patient information forms retained for analysis. Three (1. 5%) were excluded for missing data. The patients characteristics are summarized in Table  1. There were no significant differences in the number of patients designating an HCP or writing an AD throughout the period  (2008-2009, 2010, 2011-2012)  from when the information programme was introduced to the end of the study. The sex ratio was 1. 26, the average age was 64. 4 ± 15. 8 [range: 18-91] years and 73 (37. 0%) were 70 years or older. A total of 136 (69. 0%) and 61 (31. 0%) patients presented with malignant lymphoid and malignant myeloid pathologies and others, respectively. The 2-year survival rate of the entire cohort was 78.
Acknowledgements This paper originated from a dissertation presented at the  Espace Éthique , under the supervision of  Pr E. Hirsch  within the framework of a Masters Degree 2 in Ethics,  Science, Health and Society AP-HP, Paris, France. The authors are grateful to  Danièle Leboul  for her training in qualitative analysis,  Olivier Chicaud ,  Nicole Fort ,  Karen Poole  and  Lucas Jaccard  for their technical assistance.
Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan.
The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN bingepurge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3. 01×10 -  ) in SOX2OT and rs17030795 (P=5. 84×10 -  ) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5. 76×10 -6 ) between CUL3 and FAM124B and rs1886797 (P=8. 05×10 -  ) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10 -6 ), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection.
Discovery dataset We conducted a GWAS across 15 discovery datasets, comprising a total of 2,907 AN cases and 14,860 ancestrally matched controls of European origin (Table  1 ). All AN cases were female. Diagnostic determination was via semi-structured or structured interview or population assessment strategy based on DSM diagnostic criteria. Cases met DSM-IV criteria for lifetime AN (restricting or binge-purge subtype) or lifetime DSM-IV eating disorders "not otherwise specified" (EDNOS) AN-subtype (i. e. , exhibiting the core features of AN). We did not require the presence of amenorrhea as this criterion does not increase diagnostic specificity. 44, 45   iven the frequency of diagnostic crossover, a lifetime history of bulimia nervosa was allowed. 46 Exclusion criteria included the diagnosis of medical or psychiatric conditions that might have confounded the diagnosis of AN (e.
Genotyping, imputation and quality control AN cases from the 15 sites were genotyped using Illumina 660W-Quad arrays (Illumina, Inc. , San Diego, CA, USA) at the Wellcome Trust Sanger Institute. Funding was available only for genotyping AN cases. Thus, control genotypes were selected from existing datasets matched as closely as possible to the ancestry of cases and Illumina arrays as similar as possible to the 660W array (Table  S1 ). Quality control (QC) of directly typed variants was performed within each of the 15 case-control datasets (Table  S2 , Supplementary Information). Phasing and imputation was performed separately for each of the 15 datasets using a common set of single nucleotide polymorphisms (SNPs) passing QC (Table  S2 ) using the program Impute2 v2. 1. 2 (Supplementary Information).
Statistical analysis Single-SNP association analyses were performed under an additive genetic modelseparately within each of the 15 datasets (Supplementary Information). We tested for association across the autosomes and the non-pseudoautosomal region of the X chromosome. Imputation and association analysis of the non-pseudoautosomal region of the chromosome X data were based on females (2,907 AN cases and 10,594 controls). Association analyses were performed using SNPTEST v2. 2. 0  49  under an additive model and using a score test. To guard against false positives due to population stratification, we carried out association analysis within each dataset and then combined the results using meta-analysis (for the French dataset, the first principal component was added as a covariate). Fixed-effects metaanalyses were performed using GWAMA.
Replication We prioritized directly genotyped and imputed SNPs for replication based on statistical significance (P < 10 -4 ), robust QC metrics, and vicinity to plausible candidate genes. In total 96 SNPs (95 autosomal and one on chromosome X) in 66 genomic regions showed nominal evidence for association. We selected 72 independent, uncorrelated variants representing each of the 66 associated genomic regions and added 4 proxies for the most associated SNPs resulting in 76 SNPs for replication. Cluster plots of all prioritized SNPs were examined using Evoker 51 in cases and controls separately to minimize the possibility of spurious association due to genotyping error. We included 27 ancestry-informative markers (AIMs) for genotyping in the replication datasets, to guard against population stratification (Supplementary Information).
52 r replication data included 15 datasets-two existing in silico datasets and 13 datasets for de novo genotyping (Table  1 ). The in silico dataset from the USA came from an existing GWAS of AN genotyped using the Illumina HumanHap610 platform (Illumina, San Diego, CA, USA)  53  and the other in silico dataset came from Estonian Genome Center (www. biobank. ee) and was genotyped using the Illumina OmniExpress array. De novo genotyped samples included newly collected AN cases and controls from members of the GCAN and samples from the same sites as the discovery samples that had failed GWAS QC (including saliva and whole genome amplified samples). De novo SNP genotyping was carried out using the iPLEX Gold Assay (Sequenom, Inc. , San Diego, CA, USA). SNPs with poor Sequenom design metrics were replaced with high-LD proxies.
Sample and SNP QC were performed within each replication dataset. QC included checking for sex inconsistencies and exclusions based on sample call rate <80%, SNP call rate <90% and exact Hardy-Weinberg Equilibrium (HWE) p<0. 0001. In total, replication genotypes (in silico and de novo) of 76 prioritized SNPs and 27 AIMs were available from 2,677 AN cases and 8,629 controls of European ethnicity and 458 AN cases and 421 controls from Japan. Association analyses of prioritized SNPs were performed under an additive genetic model within each replication dataset with and without adjustment for AIMs. AIMs that showed nominally significant p-values for allele frequency differences between de novo typed cases and controls were used for conditional analysis (Table  S3 ). As there were no qualitative differences between these results, the main text reports the unadjusted results.
The USA replication dataset contained individuals who were related to individuals from the USA discovery dataset. As such, those samples were excluded from the discovery dataset and combined with replication USA samples to correctly account for relatedness between samples for the final global meta-analysis and sign test. Software packages GenABEL  54  and GEMMA  55  were used for replication analysis of the USA dataset. Fixed-effects metaanalysis across the replication datasets was performed using GWAMA  50  (with and without adjustment for AIMs and in samples of European ancestry only, i. e. , excluding Japan, also with and without adjustment for AIMs). We also performed meta-analyses across the discovery and replication datasets, comprising a total of 5,551 AN cases and 21,080 controls (USA discovery samples were included only once as part of the replication phase).
05 (minimum p-value was 0. 003) in the replication dataset meta-analysis (binomial P=0. 0135) (Table  S5 ). Based on 72 independent SNPs taken forward, we would expect 0. 05×72=3. 6 SNPs to reach P=0. 05 by chance. The 0. 0135 P value reflects this enrichment in signal. No signals surpassed genome-wide significance (P=5×10 -8 ) in the final global meta-analysis across all discovery and replication samples (Table  S5 ) or in the AN subtype analyses (Tables  S6-S7 ). Of critical importance, we observed significant evidence of SNP effect sizes in the replication data in the same direction as the discovery set (55/72 signals, sign test binomial P=4×10  -6  ). This enrichment was also observed for the AN restricting (58/72, P=8×10 -8 ) and binge-purge (56/72, P=1×10 -6 ) subtype analyses. These results strongly indicate that the prioritized set of variants is likely to contain true positive signals for AN but that the current sample size is insufficient to detect these effects.
05 (binomial P=0. 1906). Twenty-six of these 53 SNPs had the same direction of effect as originally reported (binomial P value=1) (Table  S12 ). Thirteen of 15 SNPs associated with extreme obesity were extracted from our dataset and 9 of these were independent. Four of these 9 SNPs had the same direction of effect as originally reported (binomial P value=1) (Table  S13 ). Three SNPs (in TMEM18, FTO and MC4R) had P<0. 05 (binomial P value=0. 0084), indicating modest enrichment of nominally associated SNPs from extreme obesity in our discovery dataset.
27 for the AN restricting subtype and 1. 28 for the AN binge-purge subtype. Given these limitations in power, our strongest indicator that larger sample sizes could detect genetic variants associated with AN was revealed in the sign tests. The strong and significant evidence for SNP effect sizes in the same direction between discovery and replication sets (P=4×10 -6 ) clearly suggests that larger sample sizes could successfully identify variants associated with AN and with the AN subtypes potentially enabling differentiation on a genetic level between restricting and binge/purge subtypes. Several genetic variants were suggestively associated with AN (P<10 -5 ) (Table  2 ). Two variants, rs9839776 in SOX2OT and rs17030795 in PPP3CA, were identified through analysis of all discovery and replication datasets.
Acknowledgements for Controls Austria. Controls in Vienna were collected with support to  Harald Aschauer  by  Österreichische Nationalbank  (ÖNB Project Nr. 5777  and  13198 ),  Austrian Science Fund  (Pr. Nr. P7639 ),  European Science Foundation  ( ESF Programme MNMI ) and  European Commission  (Biomed 1, J1182E25A). Canada. NIH  grant No. - U24 CA074783  to  S. Gallinger. This work was made possible through collaboration and cooperative agreements with the  Colon Cancer Family Registry and PIs. The content of this manuscript does not necessarily reflect the views or policies of the  National Cancer Institute  or any of the collaborating institutions or investigators in the Colon CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the  US Government or the Colon CFR.
Czech Republic. Support came from the  European Regional Development Fund  and the  State Budget of the Czech Republic (RECAMO ,  CZ. 1. 05/2. 1. 00/03. 0101 ). dbGAP  DAC. Research support to collect data and develop an application to support this project was provided by  3P50CA093459 ,  5P50CA097007 ,  5R01ES011740 , and  5R01CA133996. Germany. We thank all probands from the community-based cohorts of PopGen, KORA, and the  Heinz Nixdorf Recall (HNR)  study. This study was supported by the  German Federal Ministry of Education and Research (BMBF) , within the context of the  National Genome Research Network plus (NGFNplus) , and the  MooDS-Net  (grant  01GS08144  to S. C. ). The KORA research platform was initiated and financed by the  Helmholtz Center Munich, German Research Center for Environmental Health , which is funded by the  BMBF  and by the  State of Bavaria.