Aunt Sallie\u27s Lament

Diamond shape bound book, 24 pages, mounted color illustrations. Limited edition of 120 copies signed by Claire Van Vliet, Mary Richardson, Audrey Holden and E.D. Levitt. This edition was made using the Permalin text block of the 1993 edition by Chronicle Books.. The design was made with Ellen Dorn Levitt and Audrey Holden who did most of the assembly and made the boxes with Mary Richardson. --Colophon. Book bound in a diamond-shape with the left point blunted for the spine. Each page is a different combination of colors and geometric shapes resembling quilt blocks. Additional Japanese and handmade papers added to this edition. Issued in a drop-spine box (31 cm.) covered with quilt-type fabric.https://digitalcommons.risd.edu/specialcollections_artistsbooks/1139/thumbnail.jp

Review of endemic Sulawesi squirrels.

260 p. : ill. (some col.), maps ; 26 cm. "Issued June 11, 2010." Includes bibliographical references (p. 246-255).Analyses of fur color patterns, morphometric data derived from external, cranial, and dental dimensions, and distributions of collection sites for voucher specimens form the basis for a taxonomic revision of Sulawesi’s endemic squirrel fauna. Eight species of tree squirrels in Rubrisciurus and Prosciurillus and two species of ground squirrels in Hyosciurus are recognized. All are diurnal and inhabit primary forest formations. Diet consists of fruit, nuts, seeds, and arthropods. Rubrisciurus rubriventer, the largest in body size, forages on the ground and in the lower canopy layer, is found throughout Sulawesi where primary forest persists, and occurs through an altitudinal range embracing tropical lowland evergreen and lower montane rain forests; it is absent from upper montane rain forest. Five species of arboreal squirrels comprise the Prosciurillus leucomus group, a cluster of species occupying the upper forest canopy: P. leucomus, known only from lowland and montane habitats in the northern peninsula and one offshore island; P. alstoni, recorded from lowland tropical evergreen rain forest in the eastern section of Sulawesi’s central core, the east-central and southeastern arms, and two southeastern islands; P. weberi, represented by a few specimens from the coastal lowlands of the southern core of Sulawesi; P. topapuensis, endemic to the western mountain block in Sulawesi’s central core and occurring along an altitudinal gradient from lowland evergreen rain forest to upper montane rain forest; and P. rosenbergii, the only species of squirrel collected on islands in the Sangihe Archipelago north of the northeastern tip of the northern peninsula. The Prosciurillus murinus group contains two species of small body size: P. murinus, found throughout Sulawesi and in all forest formations, from the coastal lowlands to mountaintops, and a forager in the lower canopy layers; and P. abstrusus, known only from montane forest habitats on Pegunungan Mekongga in the southeastern peninsula. Of two species of ground squirrels, Hyosciurus heinrichi occupies montane forest habitats in the western mountain block of Sulawesi’s central core. It is altitudinally parapatric to H. ileile, which inhabits lowland evergreen and lower montane rain forests in the western mountain block and northeastern lowlands of central Sulawesi, and montane forest on the northern peninsula. A slightly revised classification of Sciuridae is provided in which a new tribe, Exilisciurini, is proposed for the Bornean and Philippine Exilisciurus. Previously published results of morphological and molecular analyses point to Rubrisciurus, Prosciurillus, and Hyosciurus as a monophyletic cluster, the Hyosciurina, nested within a larger clade, the Nannosciurini, which along with Exilisciurini n. tribe and Funambulini, comprise the Nannosciurinae, one of the three subfamilies constituting Sciuridae, and one that contains most of the Indomalayan genera. The present diversity of species endemic to Sulawesi was derived from an ancient lineage that crossed a sea barrier from the Sunda Shelf to Sulawesi during the late Miocene. Eight new species of hoplopleurid sucking lice ‪(‬Insecta, Anoplura‪)‬ are described as parasitizing 8 of the 10 species of squirrels endemic to Sulawesi: Hoplopleura rubrisciuri from Rubrisciurus rubriventer, Hoplopleura leucomus from Prosciurillus leucomus, Hoplopleura alstoni from Prosciurillus alstoni, Hoplopleura topapuensis from Prosciurillus topapuensis, Hoplopleura murinus from Prosciurillus murinus, Hoplopleura abstrusus from Prosciurillus abstrusus, Hoplopleura heinrichi from Hyosciurus heinrichi, and Hoplopleura ileile from Hyosciurus ileile. Examples of Prosciurillus weberi and P. rosenbergii were surveyed but no lice were recovered. A phylogenetic analysis based on cladistic principles for six species of Sulawesian squirrel lice for which both sexes were available is presented and the results discussed with respect to host relationships. These new data are incorporated into a discussion covering zoogeography of global sciurid-sucking louse associations, emphasizing the Indomalayan squirrel fauna. Globally, members of 11 genera of Anoplura parasitize sciurids, a figure far exceeding the number of anopluran genera associated with any other mammalian family. Nine of these ‪(‬the enderleinellids, Atopophthirus, Enderleinellus, Microphthirus, Phthirunculus, and Werneckia; the hoplopleurid, Paradoxophthirus; and the polyplacids, Johnsonpthirus, Linognathoides, and Neohaematopinus‪)‬ are primary parasites of sciurids. The remaining two ‪(‬the hoplopleurid Hoplopleura, and the polyplacid Polyplax‪)‬ include representatives that are acquired ‪(‬secondary‪)‬ parasites of sciurids--the majority of species in these two louse genera parasitize other groups of mammals but a small number of species have transferred to squirrel hosts. Sciurid hosts and geographic distributions of these 11 anopluran genera are discussed. Historically, representatives of Hoplopleura colonized different sciurid hosts on several separate occasions with one known species on a North American tree squirrel ‪(‬Sciurus‪)‬, two described species on North American flying squirrels ‪(‬Glaucomys‪)‬, two species parasitizing North American species of chipmunks ‪(‬Tamias and Eutamias‪)‬, 14 described species from Indomalayan nannosciurine squirrels ‪(‬Callosciurus, Tamiops, Rubrisciurus, Prosciurillus, Hyosciurus, and Funambulus‪)‬, and one species parasitizing a Chinese xerine ground squirrel ‪(‬Sciurotamias‪)‬. The zoogeography of the seven sciurid-infesting louse genera known from Southeast Asia is discussed using data from nine different countries or regions ‪(‬China, Taiwan, Thailand, peninsular Malaysia, Sumatra, Java, Borneo, the Philippines, and Sulawesi‪)‬. A reduction in the number of sciuirid-infesting anopluran genera and species is apparent from mainland northern/western regions to insular southern/eastern regions with members of seven genera and 23 species described from China but only one genus and eight species from Sulawesi. The absence of known species of Hoplopleura from Bornean and Javanese squirrels suggests that such a fauna may await discovery on one or both of these islands. Six of the eight species of Hoplopleura found parasitizing species of endemic Sulawesi squirrels were recovered as a monophyletic clade from a phylogenetic analysis employing anatomical structures associated with male and female lice. ‪(‬Two species of Sulawesi Hoplopleura are based on females and nymphs only and were not incorporated into the analysis.‪)‬ The monophyletic cluster formed by the Sulawesian squirrel lice joined with the monophyletic assemblage containing the three Sulawesi squirrel genera--Rubrisciurus, Prosciurillus, and Hyosciurus--suggest that the ancestral squirrel lineage that arrived in Sulawesi during the late Miocene may have been carrying its unique Hoplopleura parasite

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Contributions in honor of Guy G. Musser.

450 p. : ill. (some col.), maps ; 26 cm. "Issued December 15, 2009." Includes bibliographical references.Contents: They sort out like nuts and bolts : a scientific biography of Guy G. Musser / Michael D. Carleton -- Taxonomy, distribution, and natural history of the genus Heteromys ‪(‬Rodentia: Heteromyidae‪)‬ in central and eastern Venezuela, with the description of a new species from the Cordillera de la Costa / Robert P. Anderson and Eliécer E. Gutiérrez -- Review of the Oryzomys couesi complex ‪(‬Rodentia: Cricetidae: Sigmodontinae‪)‬ in western Mexico / Michael D. Carleton and Joaquin Arroyo-Cabrales -- The antiquity of Rhizomys and independent acquisition of fossorial traits in subterranean muroids / Lawrence J. Flynn -- A new species of Reithrodontomys, subgenus Aporodon ‪(‬Cricetidae: Neotominae‪)‬, from the highlands of Costa Rica, with comments on Costa Rican and Panamanian Reithrodontomys / Alfred L. Gardner and Michael D. Carleton -- Phylogenetic relationships of harpyionycterine megabats ‪(‬Chiroptera: Pteropodidae‪)‬ / Norberto P. Giannini, Francisca Cunha Almeida, and Nancy B. Simmons -- A new genus and species of small ‪"‬tree-mouse‪"‬ ‪(‬Rodentia, Muridae‪)‬ related to the Philippine giant cloud rats / Lawrence R. Heaney, Danilo S. Balete, Eric A. Rickart, M. Josefa Veluz, and Sharon A. Jansa -- Biodiversity and biogeography of the moss-mice of New Guinea : a taxonomic revision of Pseudohydromys ‪(‬Muridae: Murinae‪)‬ / Kristofer M. Helgen and Lauren E. Helgen -- Systematic revision of sub-Saharan African dormice ‪(‬Rodentia: Gliridae‪)‬. Part 2, Description of a new species of Graphiurus from the central Congo Basin, including morphological and ecological niche comparisons with G. crassicaudatus and G. lorraineus / Mary Ellen Holden and Rebecca S. Levine -- Descriptions of new species of Crocidura ‪(‬Soricomorpha: Soricidae‪)‬ from mainland Southeast Asia, with synopses of previously described species and remarks on biogeography / Paulina D. Jenkins, Darrin P. Lunde, and Clive B. Moncrieff -- The six opossums of Félix de Azara : identification, taxonomic history, neotype designations, and nomenclatural recommendations / Robert S. Voss, Philip Myers, François Catzeflis, Ana Paula Carmignotto, and Josefina Barreiro -- Skull and dentition of Willeumys korthi, nov. gen. et sp., a cricetid rodent from the Oligocene ‪(‬Orellan‪)‬ of Wyoming / John H. Wahlert

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Phenotypic Characterization of <i>EIF2AK4</i> Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 ( BMPR2 ) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene ( EIF2AK4 ) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. Methods: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource–Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of &lt;1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. Results: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (K co ; 33% [interquartile range, 30%–35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23–38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. Conclusions: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low K co and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation. </jats:sec

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention