John Cole of Baltimore (1774-1855): his life and works

Thesis (M.A.)--Boston UniversityJohn Cole, the son of John and Ann Cole, was born in Tewkesbury, England, where he was baptized on June 24, 1774. At an early age, he emigrated to America, and settled in Baltimore, Maryland, the seat of all his later musical activities, until his death on August 17, 1855. Despite his early training, reputedly received from contact with the singing-schools of Andrew Law, Andrew Adgate and others, Cole considered himself basically a self-taught musician. At first a writer and bookseller as well as a band musician, he eventually concentrated mainly on the composition and editing of sacred music. Much of this music was intended for the use of the Protestant Episcopal Church in the United States of America, one of the earliest instances in this country of music composed for a particular denomination. His earliest activities in church music were in connection with St. Paul's and Christ Church in Baltimore, both Episcopal, and his concern with the production of music for the services of this church is reflected in numerous publications throughout his life. Among works including compositions adapted to the Episcopal liturgy are: Sacred Music of 1803, Episcopalian Harmony of 1811, The Seraph of 1821 and 1827, Primitive Psalmody of 1836, Parochial Psalmody of 1840, Laudate Dominum of 1842 and 1847, and a collection of Chants For the Use of the Protestant Enisconal Church which is undated. Cole had ample opportunity to foster the promulgation of his own works since he was not only a composer, but also a publisher of music which he could then distribute through his own music store. In later years he was joined in this venture by his son, George Frederick Handel Cole, who was born on May 7, 1803, of the union of John and Ann Brewer Cole. The firm of John Cole & Son remained in business until 1839, when it was sold to F. D. Benteen, who then continued as the publisher of some of Cole's later works. His son continued on his own for awhile but later moved to Charleston, South Carolina, where he eventually died in 1861. Cole's reputation in the Baltimore community as a musician of high standards is attested to by several factors. As early as A Collection of Psalm Tunes and Anthems composed in 1803, Cole published an anthem entitled "Mt. Vernon" which an annotation in his own handwriting describes as "sung at the Funeral Solemnities, on the death of Washington." Many of his publications of liturgical music were done under the patronage of the Bishops and Clergy of the Episcopal Church. In 1828, he was chosen to write "a Song for the Day" in honor of the Fourth of July and the commencement of the Baltimore and Ohio railroad. His most famous hymn-tune "Geneva" appeared in innumerable collections of church music until late in the nineteenth century. Finally, his association with the celebrated Lowell Mason on an apparently equal professional footing is reflected both by the presence of Cole's works in the Lowell Mason collection and the manuscript book of hymn-tunes sent by Cole to Mason with annotations discussing matters of musical import. A survey of Cole's publications reveals his significant position as a transitional figure between the native American composers like Billings and Holden and the advocates of the "better music" movement like Mason and Hastings, who in their zeal for "taste" turned away from the native tradition and toward foreign importations. Cole started out in the traditional way, teaching singing-schools and writing tunes that incorporated many features associated with the "Fuguing-tune" composers. His growing taste for European music led him to acorn the "village musicians of the past century" and to advocate the adoption of musical practices going back to Ravenscroft and other psalmodists, and extending to Handel, Bach, Mozart, Beethoven, and a group of lesser lights originating mainly in England in the later eighteenth century. He also admired greatly the German tradition of the chorale which he felt shbuld be emulated by American composers. Cole's later works reflect his concern for spreading the "newer" taste, and include, as a result, many compositions which would not be held in esteem today. Among these are several of a sentimental, "genteel" nature, a few adapted from secular pieces, and others which show a derivative acquaintance with the works of Handel and his followers. In his better compositions, however, Cole incorporates some of the vitality of the earlier American tradition, which he remembered throughout his life. He even goes back to the "sharpe-note" or "patent-note" tradition in his Union Harmony of 1829, decrying his previous prejudices against this system. He is also not averse to introduce sections of imitation in the best "fuguing-tune" tradition in a composition of a neo-Handelian cast like the anthem "O Be Joyful in the Lord" from Devotional Harmony. The dichotomy between old and new is seen clearly in the pages of The Rudiments of Music especially in the matter of performance practice. Proportional concepts of time-signatures and ornamentation practices of the early eighteenth century stand side by side with Romantic concern with text as the point of departure for musical interpretation, and the use of descriptive terminology for tempo, plus clear indication of the nuances and dynamics necessary for performance. In sum, John Cole will not take his place in American music history as an unsung genius or an extraordinarily gifted composer. Nevertheless many practices instituted by him take on new meaning when the struggle to establish these practices in the past is examined critically in the light of the present problems of church musicians. And no more objective clue to the daily musical life of a people can be found than in the analysis of the activities of an average, devoted practitioner of the art of music examined in the hum-drum exposition of his everyday commitments. The work of Cole, coupled with the sincere efforts of countless others, has contributed to the broad stream of musical culture which is the basis of our present-day achievements in this area, and for this reason alone, are these earlier efforts worthy of investigation

Evolutionary approaches to epistemic justification

What are the consequences of evolutionary theory for the epistemic standing of our beliefs? Evolutionary considerations can be used to either justify or debunk a variety of beliefs. This paper argues that evolutionary approaches to human cognition must at least allow for approximately reliable cognitive capacities. Approaches that portray human cognition as so deeply biased and deficient that no knowledge is possible are internally incoherent and self-defeating. As evolutionary theory offers the current best hope for a naturalistic epistemology, evolutionary approaches to epistemic justification seem to be committed to the view that our sensory systems and belief-formation processes are at least approximately accurate. However, for that reason they are vulnerable to the charge of circularity, and their success seems to be limited to commonsense beliefs. This paper offers an extension of evolutionary arguments by considering the use of external media in human cognitive processes: we suggest that the way humans supplement their evolved cognitive capacities with external tools may provide an effective way to increase the reliability of their beliefs and to counter evolved cognitive biases

The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

This corrects the article DOI: 10.1038/ncomms5999