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Missense Variants in ATM in 26,101 Breast Cancer Cases and 29,842 Controls
Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Nick Orr, Alan Ashworth, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Barbara Burwinkel, Claus R. Bartram, Alfons Meindl, Rita K. Schmutzler, Angela Cox, Ian Brock, Graeme Elliott, Malcolm W.R. Reed, Melissa C. Southey, Letitia Smith, Amanda B. Spurdle, John L. Hopper, Fergus J. Couch, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Peter Schürmann, Regina Waltes, Michael Bremer, Thilo Dörk, Peter Devilee, Christie J. van Asperen, Rob A.E.M. Tollenaar, Caroline Seynaeve, Per Hall, Kamila Czene, Keith Humphreys, Jianjun Liu, Shahana Ahmed, Alison M. Dunning, Melanie Maranian, Paul D.P. Pharoah, Georgia Chenevix-Trench, Jonathan Beesley, Natalia V. Bogdanova, Natalia N. Antonenkova, Iosif V. Zalutsky, Hoda Anton-Culver, Argyrios Ziogas, Hiltrud Brauch, Yon-Dschun Ko, Ute Hamann, Peter A. Fasching, Reiner Strick, Arif B. Ekici, Matthias W. Beckmann, Graham G. Giles, Gianluca Severi, Laura Baglietto, Dallas R. English, Roger L. Milne, Javier Benítez, José Ignacio Arias, Guillermo Pita, Børge G. Nordestgaard, Stig E. Bojesen, Henrik Flyger, Daehee Kang, Keun-Young Yoo, Dong Young Noh, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Montserrat García-Closas, Stephen Chanock, Jolanta Lissowska, Louise A. Brinton, Jenny Chang-Claude, Shan Wang-Gohrke, Annegien Broeks, Marjanka K. Schmidt, Flora E. van Leeuwen, Laura J. Van't Veer, Sara Margolin, Annika Lindblom, Manjeet K. Humphreys, Jonathan Morrison, Radka Platte, Douglas F. Easton and Julian Peto
Olivia Fletcher
Nichola Johnson
Isabel dos Santos Silva
Nick Orr
Alan Ashworth
Heli Nevanlinna
Tuomas Heikkinen
Kristiina Aittomäki
Carl Blomqvist
Barbara Burwinkel
Claus R. Bartram
Alfons Meindl
Rita K. Schmutzler
Angela Cox
Ian Brock
Graeme Elliott
Malcolm W.R. Reed
Melissa C. Southey
Letitia Smith
Amanda B. Spurdle
John L. Hopper
Fergus J. Couch
Janet E. Olson
Xianshu Wang
Zachary Fredericksen
Peter Schürmann
Regina Waltes
Michael Bremer
Thilo Dörk
Peter Devilee
Christie J. van Asperen
Rob A.E.M. Tollenaar
Caroline Seynaeve
Per Hall
Kamila Czene
Keith Humphreys
Jianjun Liu
Shahana Ahmed
Alison M. Dunning
Melanie Maranian
Paul D.P. Pharoah
Georgia Chenevix-Trench
Jonathan Beesley
Natalia V. Bogdanova
Natalia N. Antonenkova
Iosif V. Zalutsky
Hoda Anton-Culver
Argyrios Ziogas
Hiltrud Brauch
Yon-Dschun Ko
Ute Hamann
Peter A. Fasching
Reiner Strick
Arif B. Ekici
Matthias W. Beckmann
Graham G. Giles
Gianluca Severi
Laura Baglietto
Dallas R. English
Roger L. Milne
Javier Benítez
José Ignacio Arias
Guillermo Pita
Børge G. Nordestgaard
Stig E. Bojesen
Henrik Flyger
Daehee Kang
Keun-Young Yoo
Dong Young Noh
Arto Mannermaa
Vesa Kataja
Veli-Matti Kosma
Montserrat García-Closas
Stephen Chanock
Jolanta Lissowska
Louise A. Brinton
Jenny Chang-Claude
Shan Wang-Gohrke
Annegien Broeks
Marjanka K. Schmidt
Flora E. van Leeuwen
Laura J. Van't Veer
Sara Margolin
Annika Lindblom
Manjeet K. Humphreys
Jonathan Morrison
Radka Platte
Douglas F. Easton
Julian Peto
DOI: 10.1158/1055-9965.EPI-10-0374 Published September 2010
Background: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious.
Methods: We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense single nucleotide polymorphisms (SNP) in ATM (S49C, S707P, F858L, P1054R, and L1420F) in 26,101 breast cancer cases and 29,842 controls from 23 studies in the Breast Cancer Association Consortium.
Results: Combining the data from all five SNPs, the odds ratio (OR) was 1.05 for being a heterozygote for any of the SNPs and 1.51 for being a rare homozygote for any of the SNPs with an overall trend OR of 1.06 (Ptrend = 0.04). The trend OR among bilateral and familial cases was 1.12 (95% confidence interval, 1.02-1.23; Ptrend = 0.02).
Conclusions: In this large combined analysis, these five missense ATM SNPs were associated with a small increased risk of breast cancer, explaining an estimated 0.03% of the excess familial risk of breast cancer.
Impact: Testing the combined effects of rare missense variants in known breast cancer genes in large collaborative studies should clarify their overall contribution to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 19(9); 2143–51. ©2010 AACR.
This article is featured in Highlights of This Issue, p. 2113
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, radiosensitivity, and a predisposition to malignancy (MIM #208900). The gene that is mutated in A-T, ATM (MIM #607585), encodes a protein kinase that plays a key role in cellular responses to DNA damage. The large majority of A-T cases are known to harbor mutations in ATM leading to a truncated or absent protein. Epidemiologic studies of families of A-T patients have shown a 2- to 5-fold increased risk of breast cancer for female relatives who are obligate heterozygous carriers of an A-T mutation (1, 2).
The increased risk of breast cancer in ATM mutation carriers has been confirmed by direct analysis of ATM mutations in breast cancer cases compared with controls. In a study of British familial breast cancer cases and controls, Renwick and colleagues identified 9 mutations that result in premature termination or exon skipping among 443 strongly familial cases (2.0%) compared with 2 in 551 controls (0.4%, P = 0.028; ref. 3). They also found three cases and no controls who carried one of two missense variants for which there is strong a priori evidence of a pathogenic phenotype in individuals with A-T (V2424G or SV2855_2856RI). Bernstein and colleagues identified 7 heterozygotes for the V2424G missense variant among 3,743 population-based breast cancer cases (0.2%) unselected for family history and none among 1,268 controls (P = 0.1; ref. 4). Based on the breast cancer history of first- and second-degree relatives of carrier cases, the breast cancer risk to age 70 years for heterozygotes was estimated to be 52% [95% confidence interval (95% CI), 28-80%; P < 0.0001].
An association between other ATM variants, particularly amino acid substitutions that are not expected to be associated with A-T, and breast cancer has also been hypothesized (5), but to date, there has been little evidence to support this (6, 7). In a previous study, we genotyped nine missense variants in ATM in 473 bilateral breast cancer cases and 2,463 controls as part of a high-throughput screen of 1,037 nonsynonymous single-nucleotide polymorphisms (SNP) within candidate "cancer genes" (8). None of these variants was common, with minor allele frequencies (MAF) in controls ranging from <0.1% (0 of 4,924 chromosomes) to 2.4% (116 of 4,926 chromosomes). Although no single ATM missense variant was significantly associated with breast cancer risk, there was a significant trend in risk with increasing numbers of variant ATM SNPs [odds ratio (OR), 1.27; 95% CI, 1.04-1.56; Ptrend = 0.02]. We selected four variants with MAF >1% [S707P (rs4986761), F858L (rs1800056), P1054R (rs1800057), and L1420F (rs1800058)] for further analysis in 26,101 invasive breast cancer cases and 29,842 controls in 23 studies within the Breast Cancer Association Consortium (BCAC). We also included a fifth variant [S49C (rs1800054)] with a MAF of 1.2%, which was not genotyped in our previous analysis (8) but for which there had been some prior evidence of an association with breast cancer risk (OR, 1.13; 95% CI, 0.99-1.30 P = 0.08) in an earlier BCAC analysis (9) that included a subset of the current studies.
Study populations and genotyping
Supplementary Table S1 summarizes the study details and genotyping platform for all studies that contributed data. Genotyping was done with 5′ nuclease assay (TaqMan), Sequenom iPLEX, or Illumina Golden Gate technology. TaqMan genotyping reagents were designed by Applied Biosystems as Assays-by-DesignSM and distributed by the University of Cambridge group to each of the centers that used this technology. Genotyping was done using the ABI PRISM 7900HT or 7500 Sequence Detection System according to the manufacturer's instructions. For five studies, SNPs were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for the determination of allele-specific primer extension products using the Sequenom MassARRAY system and iPLEX technology. The design of oligonucleotides was carried out according to the guidelines of Sequenom and performed using MassARRAY Assay Design software (version 1.0). In one study, SNPs were genotyped using customized Illumina Sentrix Bead Arrays according to the manufacturer's instructions.
Quality control criteria
We applied BCAC standard quality control (QC) guidelines (http://www.srl.cam.ac.uk/consortia/bcac/). In addition, we imposed a threshold of 99% for the call rate (compared with the standard threshold of 95%) and we excluded SNPs from studies where cluster plots, scored from 1 (poor) to 4 (good), scored by a single reader blinded to identifiers, scored 2 or less. These more stringent thresholds were imposed because the minor alleles of these SNPs are rare and therefore more susceptible to differential calling between cases and controls. S49C was not genotyped by 3 studies and data were excluded from analyses for QC criteria for 3 studies. S707P was not genotyped by 2 studies and data were excluded from analyses for QC criteria for 8 studies. F858L was genotyped by all studies; data were excluded from analyses for QC criteria for 1 study. P1054R was genotyped by all studies and data were excluded from analyses for QC criteria for 3 studies. L1420F was not genotyped by 2 studies and data were excluded from analyses for QC criteria for 8 studies. The full details of the studies that contributed data for each SNP, the numbers of cases and controls genotyped by each study, and the genotypes of cases and controls for each SNP are given in Supplementary Tables S1 and S2.
Statistical methods
The OR for each SNP and for being a carrier or rare homozygote for any SNP was tested using logistic regression with "study" as a stratifying covariate. To maximize the amount of data included in the analysis, SNPs that were not genotyped by a study or were excluded for QC criteria were coded as 0 for all subjects for the analysis of being a carrier or rare homozygote for any SNP. The effect of this will be to bias our OR estimate, marginally, toward the null.
Linkage disequilibrium metrics between SNPs (r2 and D′; Supplementary Table S3) were computed separately for each study using the Tagzilla module as implemented in GLU version 1.0a6. rs1800056 (F858L) and rs1800057 (P1054R) are correlated (r2 = 0.38-0.71; Supplementary Table S3), otherwise these rare SNPs are independent of each other (r2 < 0.001). Maximum likelihood estimates of haplotype frequencies for the four alleles defined by F858L and P1054R (i.e. F858+P1054, F858+1054R, 858L+1054R, and 858L+P1054) were estimated in cases and controls separately and in each of the studies separately using HaploStats (http://mayoresearch.mayo.edu/mayo/research/schaid_lab/software.cfm); Supplementary Table S3). ORs for F858+1054R, 858L+1054R, and 858L+P1054 versus the common allele F858+P1054 were estimated using unconditional logistic regression weighted for the phase assignment probability and with study as a stratifying covariate.
Statistical analyses were done using STATA version 10 (State College). All P values reported are two-sided. Meta-analyses (Fig. 1) were carried out using the Metan routine within STATA, using inverse variance weighting of the study specific estimates. Cochran's Q statistic and the I2 statistic (10) to quantify the proportion of the total variation due to heterogeneity between studies were calculated.
Trend OR estimates for S49C, S707P, F858L, P1054R, and L1420F combined by study in all cases and all controls (A) and in bilateral cases and cases with a family history of breast cancer and all controls (B). ORs and Ptrends were calculated, coding individuals who were common homozygotes for all genotyped SNPs as 0, individuals who were heterozygous for any rare variant as 1, and individuals who were rare homozygotes as 2 (statistical methods). Horizontal lines, 95% CIs. Diamond, combined, fixed-effects estimate of the OR and 95% CI. Vertical line, null effect (OR, 1.0).
The distribution of genotypes in cases and controls in each study for each ATM SNP is shown in Supplementary Table S2. Subjects reporting ethnicities other than Caucasian were excluded (see footnote in Supplementary Table S2). The MAFs for each of the five SNPs genotyped in this analysis differed significantly (P < 0.007; see footnote in Supplementary Table S1) among the 22 studies of Caucasian subjects; medians (ranges) were S49C, 1.2% (0.2-1.7%); S707P, 0.9% (0.6-1.6%); F858L, 1.5% (0.2-2.4%); P1054R, 2.6% (0.6-3.7%); and L1420F, 1.6% (0.2-2.7%). In the study in which the majority of subjects were of Asian ethnicity (SEBCS), three SNPs were monomorphic (S49C, S707P, and F858L), and for the other two SNPs (P1054R and L1420F), there was only one carrier among 872 control subjects.
In the combined analysis across studies, the point estimates for each of the heterozygote ORs were above 1.0 and the estimates of the homozygote ORs were higher (Table 1). The only significantly elevated OR was for L1420F homozygotes (5.31; 95% CI, 1.35-20.87). Two SNPs, F858L (rs1800056) and P1054R (rs1800057), are correlated (r2 = 0.38-0.71 across studies; Supplementary Table S3). The G allele of rs1800057 (1054R) is more common than the C allele of rs1800056 (858L; Supplementary Table S2); thus, the rare C allele of rs1800056 (858L) is almost completely contained on the rare G allele of rs1800057 (1054R) such that there are three main haplotypes for these two allelic variants (F858_P1054, F858_1054R, and 858L_1054R) and one extremely rare haplotype (858L_P1054; Supplementary Table S3). The trend OR estimates for each of the two haplotypes that carried the rare (C) allele of rs1800056 (858L_1054R and 858L_P1054) compared with the most common haplotype (F858_P1054) were 1.05 (95% CI, 0.95-1.16; P = 0.47) and 1.12 (95% CI, 0.61-2.05; P = 0.71), respectively. The OR estimate for the haplotype that carried the rare (G) allele of rs1800057 with the common T allele of rs1800056 (F858_1054R) was 0.97 (95% CI; 0.86-1.10, P = 0.65).
Summary heterozygote, homozygote, and trend ORs for S49C, S707P, F858L, P1054R, and L1420F
Combining the data from all five SNPs, the OR was 1.05 for being a heterozygote for any of the SNPs and 1.51 for being a rare homozygote for any of the SNPs (Ptrend = 0.04), with an overall ORtrend of 1.06 (Table 1) and no evidence of heterogeneity between studies (Fig. 1A; Cochrane Q = 21.5 21df, P = 0.43, I2 = 2.4%). Restricting the analysis to bilateral cases and those with a family history of breast cancer, the overall ORtrend was stronger (ORtrend, 1.12; Ptrend = 0.02; Table 1) with no evidence of heterogeneity between studies (Fig. 1B; Cochrane Q = 15.5 18df, P = 0.62, I2 = 0%).
Based on Swift's demonstration that carrier status for recessively inherited A-T is associated with a 3-fold increase in risk of female breast cancer (1) and on the more recent molecular validation of this observation (3), it is arguable that there is a high prior likelihood that a subset of polymorphic (MAF >1%) missense ATM variants will be associated with a modest increase in breast cancer risk. In our previous analysis of the combined effects of nine missense ATM variants (MAF <0.1-2.4%), we showed that, on average, each missense ATM SNP was associated with an OR of 1.27 (95% CI, 1.04-1.56) in bilateral breast cancer cases, implying an OR of 1.13 (95% CI, 1.02-1.25) for cases with a single primary breast cancer (11, 12).
We selected five SNPs for further investigation. Despite restricting our follow-up analysis to SNPs with MAFs estimated to be ≥1%, we did not have power to estimate the individual effects for these SNPs or the effects of individual haplotypes. The aim of this present analysis was, therefore, to test the composite hypothesis that rare polymorphic ATM variants are, on average, associated with an increased risk of breast cancer. The five SNPs we genotyped in this analysis had a combined carrier frequency of ∼12.5%; by genotyping 20,000 cases and 20,000 controls, we had 90% power at 1% significance to detect an OR of 1.10.
Our OR estimate of 1.06 (95% CI, 1.00-1.12) provides independent evidence that polymorphic missense variants in ATM are associated with a very modest increase in breast cancer risk, albeit at a nominal level of statistical significance (P = 0.04). The stronger OR estimate for bilateral cases and cases with a family history of breast cancer (OR, 1.12; 95% CI, 1.02-1.23; P = 0.02) provides additional support.
We identified four previous studies (13-16) in which at least 100 Caucasian breast cancer cases and 100 Caucasian controls were genotyped and for which individual effect sizes for S49C (rs1800054), S707P (rs4986761), F858L (rs1800056), P1054R (rs1800057), or L1420F (rs1800058) were reported (Table 2); we also obtained data for all five variants from the Wellcome Trust Case Control Consortium analysis (Table 2, ref. 17). For three of these (13, 14, 16), the case control series overlap with the current analysis; the other two (15, 17) do not support an association but are entirely consistent with a per-SNP OR of 1.06. A recent analysis of rare (MAF <1%), evolutionarily unlikely missense substitutions in ATM (18) reported a per-SNP OR estimate of 1.14 (95% CI, 0.90-1.44; P = 0.39) for the combined effects of 121 variants in 1,948 cases and 1,852 controls. We also identified two studies that compared the frequency of ATM variants in bilateral breast cancer cases versus unilateral breast cancer cases. One (19) reported no difference in the frequency of missense variants between bilateral cases and unilateral cases overall but a longer median time to developing a second cancer in carriers of a missense variant who also received radiotherapy. In the other (20), a study of gene-environment interactions (WECARE study) in which bilateral cases were counter-matched to unilateral "controls" on the basis of exposure to radiotherapy, rare (MAF <1%) A-T associated variants and those that were classified as deleterious according to the prediction algorithm SIFT (21) were associated with a nonsignificantly increased risk of a second breast cancer, whereas those that were classified as tolerated and several of the more common missense variants were associated with a protective effect. For the linked variants F858L and P1054R, this was statistically significant [OR, 0.5 (95% CI, 0.3-1.0) and 0.5 (95% CI, 0.3-0.9) for F858L and P1054R, respectively], raising the possibility of an interaction between radiotherapy and a subset of ATM variants.
Summary of previously published and publicly accessible data on S49C, S707P, F858L, P1054R, and L1420F
It is not yet clear whether polymorphic (MAF >1%) missense variants in ATM and other validated breast cancer genes could make a contribution to explaining the excess familial risk of breast cancer. With a combined carrier frequency of 12.6% in Caucasian controls and an estimated average OR of 1.06, these five ATM variants explain 0.03% of excess familial risk of breast cancer, compared with between 0.07% and 1.7% explained by each of the common variants identified in recent genome-wide association studies (7, 22-27). Rare SNPs (MAF ≤5%), however, account for a relatively large proportion of genetic variation (28); there are 83 rare missense SNPs in ATM listed in dbSNP (including the five genotyped in this study) and large numbers in other breast cancer genes (29-32).
Testing the combined effects of rare missense variants in known breast cancer genes in large collaborative studies should, eventually, clarify their overall contribution to breast cancer susceptibility. Gutierrez-Enriquez et al. (33) compared the radiosensitivity of lymphoblastoid cell lines (LCL) from breast cancer cases who were carriers of one or more rare allele(s) of S707P, F858L, P1054R, and L1420F to that of LCLs from healthy controls. They showed increased radiosensitivity in the LCLs from the breast cancer cases compared with the LCLs from controls generally, and specifically for the six LCLs from patients with at least one copy of the 858L + 1054R haplotype. Incorporating information from such functional assays and from next-generation in silico prediction algorithms may help to identify a subset that are most likely to be predictive of risk (34-36).
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
We thank the thousands of women who participated in this research. The HEBCS thanks Dr. Kirsimari Aaltonen and RN Hanna Jäntti for their help with the patient data and gratefully acknowledges the Finnish Cancer Registry for the cancer data. The GC-HBOC thanks Sandrine Tchatchou for participating in genotyping. The SBCS thanks Sabapathy Balasubramanian, Simon Cross, Helen Cramp, and Dan Connley for their contribution to the study. The ABCFS thanks Maggie Angelakos, Judi Maskiell, and Gillian Dite. The HABCS and HMBCS gratefully acknowledge their German colleague Johann H. Karstens for his support of the breast cancer studies at Hannover Medical School. The ORIGO study thanks P.E.A. Huijts, E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. The SEARCH study thanks the SEARCH and EPIC teams for recruitment of case patients and control subjects. kConFab thanks Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, the Clinical Follow-Up Study for its contributions to the resource, and the many families who contribute to kConFab. The AOCS Management Group (D. Bowtell, G. Chenevix-Trench, A. de Fazio, D. Gertig, A. Green, and P. Webb) gratefully acknowledges the contribution of all the clinical and scientific collaborators, the AOCS, and the ACS Management Group (A. Green, P. Parsons, N. Hayward, P. Webb, D. Whiteman), as well as all of the project staff, collaborating institutions, and study participants. The GENICA study acknowledges Christian Baisch for the collection of clinical and histopathologic data; Beate Pesch, Volker Harth, and Thomas Brüning for their involvement in the recruitment of study subjects and the collection of epidemiologic data; and Christina Justenhoven for genotyping and data management. The CNIO-BCS thanks Primitiva Menendez from the Hospital Central Universitario de Asturias (HUCA-Oviedo), Pilar Zamora from the La Paz University Hospital in Madrid, and Anna González-Neira, Charo Alonso, and Tais Moreno from the CNIO. The KBCP is thankful to Helena Kemiläinen and Aija Parkkinen for their contribution. The PBCS thanks Drs. Neonila Szeszenia-Dabrowska and Beata Peplonska of the Nofer Institute of Occupational Medicine (Lodz, Poland), Witold Zatonski of the Department of Cancer Epidemiology and Prevention, The M. Sklodowska-Curie Cancer Center and Institute of Oncology (Warsaw, Poland), Mark Sherman from the Division of Cancer Epidemiology and Genetics of the National Cancer Institute (USA), Jeff P Struewing from the National Human Genetics Research Institute (USA), and Pei Chao from Information Management Services (Sliver Spring, MD) for their valuable contributions to the study. The GESBC thanks Ursula Eilber for competent data coordination and management and Tanja Koehler for excellent technical assistance. The ABCS acknowledges L. Braaf, R. van Hien, R. Tollenaar, and the other contributors to the "BOSOM" study and H.B. Bueno-de-Mesquita for support in organizing the release of control DNA.
Grant Support: The BBCS is funded by Cancer Research UK (CR-UK) and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre and the National Cancer Research Network. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland grant 110663, the Finnish Cancer Society, and the Sigrid Juselius Foundation. The GC-HBOC study was supported by Deutsche Krebshilfe grant 107054, the Center of Molecular Medicine, Cologne, the Helmholtz Society, and the Dietmar-Hopp Foundation. The SBCS was supported by Yorkshire Cancer Research and the Breast Cancer Campaign. The ABCFS was supported by National Health and Medical Research Council of Australia (NHMRC) grant 145604, NIH grant CA102740-01A2, and National Cancer Institute, NIH grant CA-95-011 through cooperative agreements with members of the Breast Cancer Family Registry and principal investigators, Cancer Care Ontario grant CA69467, Columbia University grant CA69398, Fox Chase Cancer Center grant CA69631, Huntsman Cancer Institute grant CA69446, Northern California Cancer Center grant CA69417, and University of Melbourne grant CA69638. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of collaborating centers in the Breast CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the Breast CFR. The ABCFS was initially supported by the NHMRC, the New South Wales Cancer Council, and the Victorian Health Promotion Foundation. J.L. Hopper is an Australia Fellow of the NHMRC and Victorian Breast Cancer Research Consortium Group Leader. M.C. Southey and A.B. Spurdle are Senior Research Fellows of the NHMRC. Genotyping was in part supported by the Prostate Cancer Foundation of Australia. The MCBCS was supported by NIH grants CA122340 and CA128978, an NIH Breast Cancer Specialized Program of Research Excellence award to the Mayo Clinic (CA116201), and a Susan G. Komen Breast Cancer Foundation award. The HABCS was supported by an intramural grant from Hannover Medical School and German Research Foundation (DFG) grant Do761/2-1. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (N. Bogdanova) and the Friends of Hannover Medical School (N. Bogdanova). The ORIGO study was supported by the Dutch Cancer Society. The SASBAC study was supported by the Agency for Science, Technology and Research of Singapore (A*STAR), the NIH, and the Susan G. Komen Breast Cancer Foundation. SEARCH is funded by CR-UK programme grant C490/A11021. A.M. Dunning is supported by CR-UK grant C8197/A10865 and P.D.P. Pharoah is a Senior Clinical Research Fellow of CR-UK. kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by NHMRC grants 145684, 288704, and 454508. Financial support for the AOCS was provided by U.S. Army Medical Research and Materiel Command grant DAMD17-01-1-0729, the Cancer Council of Tasmania, Cancer Foundation of Western Australia, and NHMRC grant 199600. G. Chenevix-Trench is supported by the NHMRC. The UCIBCS is supported by NIH, National Cancer Institute grant CA-58860 and Lon V Smith Foundation grant LVS-18840. The GENICA study was supported by the German Human Genome Project and German Federal Ministry of Education and Research (BMBF) grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114. Genotyping analysis was supported by the Robert Bosch Foundation of Medical Research, Stuttgart, Germany, and the Deutsches Krebsforschungszentrum, Heidelberg, Germany. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. Infrastructure support for the MCCS recruitment and follow-up is provided by The Cancer Council Victoria, whereas cohort recruitment was partly funded by VicHealth. This work using the MCCS was supported by NHMRC grants 209057, 251533, and 396414 and genotyping was in part supported by the Prostate Cancer Foundation of Australia. The CNIO-BCS was supported by the Genome Spain Foundation, the Red Temática de Investigación Cooperativa en Cáncer, the Asociación Española Contra Cáncer, and Fondo de Investigación Sanitario grants PI081120 (J. Beesley) and PI081583 (R.L. Milne.). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Copenhagen University Hospital, Herlev Hospital. The SEBCS was supported National Research and Development (R&D) Program for Cancer Control grant 0620410-1 and Korea Health 21 R&D Project grant AO30001, Ministry of Health and Welfare, Republic of Korea. The KBCP is supported by the EVO funds of Kuopio University Hospital and the Finnish Cancer Foundation. The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services. The GESBC was supported by Deutsche Krebshilfe e.V. grant 70492. Funding for the ABCS was provided by Dutch Cancer Society grants NKI 2001-2423 and 2007-3839 and the Dutch National Genomics Initiative. KARBAC acknowledges funding from the Swedish Cancer Society and the Gustav V Julilee Foundation. The BCAC is funded by CR-UK grants C1287/A10118 and C1287/A7497. Meetings of the BCAC have been funded by the European Union COST Programme (BM0606). D.F. Easton is a Principal Research Fellow of CR-UK.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).
The Breast Cancer Association Consortium writing committee for this article was composed of O. Fletcher, N. Johnson, I. dos Santos Silva, N. Orr, A. Ashworth, and J. Peto.
BCAC: http://www.srl.cam.ac.uk/consortia/bcac/; Applied Biosystems: http://www.appliedbiosystems.com/; dbSNP: http://www.ncbi.nlm.nih.gov/projects/SNP/; Australian Ovarian Cancer Study: http://www.aocstudy.org/
Received April 8, 2010.
Revision received May 28, 2010.
Accepted June 28, 2010.
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. Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry. Hum Mutat 2006;27:1122–8.
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. No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer. Breast Cancer Res 2002;4:R15.
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. The relationship between twenty missense ATM variants and breast cancer risk: the Multiethnic Cohort. Cancer Epidemiol Biomarkers Prev 2003;12:733–8.
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. Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. Am J Hum Genet 2009;85:427–46.
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. The spectrum of ATM missense variants and their contribution to contralateral breast cancer. Breast Cancer Res Treat 2008;107:243–8.
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. p53 polymorphisms: cancer implications. Nat Rev Cancer 2009;9:95–107.
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. Functional consequences of ATM sequence variants for chromosomal radiosensitivity. Genes Chromosomes Cancer 2004;40:109–19.
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. Assessing pathogenicity: overview of results from the IARC Unclassified Genetic Variants Working Group. Hum Mutat 2008;29:1261–4.
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Vladimir Sinelnikov Presents WORLD WAR III: "The Terror Casino" September 26, 2008
Washington, D.C., District of Columbia 20045
Vladimir Sinelnikov will present World War III:"The Terror Casino" in the Peter Zenger room of the National Press Club on Friday, September 26th from 4-6 pm. Sinelnikov's new one-hour documentary presents a challenging Russian perspective on the origins and ideology of international terror, one seldom seen in the West. Following the screening, blogger (laurencejarvikonline) and filmmaker Laurence Jarvik (Who Shall Live and Who Shall Die?) will moderate a panel discussion with the filmmaker and Novoye Russkoye Slovo critic Oleg Sulkin.
Sinelnikov is a leading Russian filmmaker, having written, directed, and/or produced over 100 films for television including Tetralogy The Bell of Chernobyl ("shelved" by Soviet censors), about nuclear disaster; The Academician Sakharov – a Man for all Times, about Russia's Nobel Prize-winning dissident; and Oh, Russia, My Russia...People and Power, Artist and Power, about the return of emigre producer Yuri Lubimov to complete his production of Boris Godunov in the Taganka Theatre—a rehearsal interrupted by Lubimov's flight from the USSR ten years earlier; and Mirages and Hopes, about Russian emigration to Israel.
Among Sinelnikov's subjects in World War III:"The Terror Casino" are politicians, religious leaders, scholars, secret service agents, as well as family members of terror victims and those struggling with terror in Muslim nations. It features interviews with Russians such as Mikhail Gorbachev and Alexander Yakovlev (his last interview), Kyrgyz author Chingiz Aitmatov, and Palestinian leaders including Sami Abu-Zuchri, press-secretary of HAMAS. In addition there are interviews with Zbigniew Brzezinski, Rudolph Giuliani, Henry Kissinger, Benjamin Netanyahu, and Nathan Sharansky. Finally, there is testimony from family members of terror victims.
The filmmaker will present, introduce and discuss World War III:"The Terror Casino" with the audience and panel from 4pm to 6pm. Light refreshments will be served. Audio and video recording is permitted.
The National Press Club is located at 529 14th Street NW, Washington, DC 20004, at the corner of 14th & F Street, NW, at Metro Center. Seating is limited. To reserve a seat, please email lajarvik@gmail.com with the subject line "RSVP Sinelnikov," before noon Friday, September 26th.
This event is presented in cooperation with Clotho Studio and the Russian-American Arts Foundation.
Added by LaurenceJarvik on September 24, 2008
LaurenceJarvik

redpajama_set_name: RedPajamaCommonCrawl


text:
Bishops Call for Inquiry into Mine Violence
Southern African Catholic Bishops' Conference condemned the killings at platinum mine in Marikana and called for a judicial inquiry into the circumstances that led to the violence. Thirty-four people died and 78 were injured Aug. 16 when police opened fire on striking miners who, armed with machetes and homemade spears, were gathered on a rocky outcrop at the mine, 60 miles northwest of Johannesburg. Another 10 people, including two policemen, had already been killed in violence at the mine since the start of an illegal strike Aug. 10.
Kevin Dowling, Bishop of Roman Catholic Diocese of Rustenburg
"The senseless loss of life, especially through wanton violence, is always a tragedy and needs to be condemned in the strongest terms," the Southern African Catholic Bishops' Conference said in an Aug. 17 statement. "There are a lot of questions and not many answers," Kevin Dowling, Bishop of Roman Catholic Diocese of Rustenburg said in an Aug. 17 telephone interview.
The mine is located in his diocese. He and other church leaders were aware of the standoff between two trade unions over recognition agreements at the mine and "hoped that it would be resolved in the negotiations during the week," Bishop Dowling said. The miners were also demanding higher wages. The actions of the trade unions, the London-based Lonmin mining company and the police "need to be investigated" by an inquiry that also looks at "the living and working conditions at this mining operation," the bishops said.


text:
Shelter In Place Updates
About St. Timothy's
Worship at St. Tim's
Outreach at St. Tim's
SMUM
About St. Tim's Preschool
Apply to St. Tim's Preschool
< Return to Resources page
Disaster Preparedness at St. Tim's
Note: Additional information will be posted in the coming months. Contact Dave Wilde, the Congregational Disaster Coordinator, if you have any questions or comments. The St. Timothy's Disaster Preparedness Plan ("Plan") is established:
In accordance with the guidance from the Episcopal Relief and Development U.S. Disaster Program
At the direction of Bishop Mary Gray-Reeves, Diocese of El Camino Real; and,
With the approval of the Vestry of St. Timothy's Episcopal Church.
This Plan covers all St. Timothy's staff members and official church functions and operations. This plan is also meant to cover non-staff personnel and non-church related functions to the extent feasible. All St. Timothy's staff members are expected to operate in compliance with the plan and are responsible for assisting with its implementation. It is intended that this Plan will be communicated to all personnel and groups who use the facility, but the Plan does not necessarily supersede the specific emergency procedures established by other organizations (e.g., St. Timothy's Preschool, Champion Youth Enrichment School).
This Plan is intended to provide for the overall safety of people and property at the St. Timothy's Episcopal Church facility. This plan covers a variety of topics related to personnel safety, emergency preparedness, security, and loss prevention.
Disaster Leadership Team
The Congregational Disaster Coordinator provides leadership and guidance to the congregation in advance of, during, and following an emergency, and leads the Disaster Leadership Team (DLT). The Disaster Leadership Team supports the Coordinator and the congregation in preparedness and response efforts.
Current Team Members:
Kandace Klemba
Bill Rankin
Grace Schmidt
Bill Shreve
Dave Wilde (coordinator)
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text:
Q: How to add JavaScript chart to HTML document, conditionally? I've got a function that takes in a number variable and produces a gauge based on the variable.
function gaugeProgress(number) {
    percent = number;
    barWidth = 40;
    numSections = 3;
    ...
};

This is the original gauge: https://codepen.io/jaketrent/pen/eloGk although a few changes have been made.
I've then got another long function that only occurs once an input is made and a button is clicked.
I originally had the follow if/else statement, to determine if the input matched, and to add a message to the HTML document if it did.
 if(x = xyz) {
     addHTML += '
blah
'
 } else if (x = yz) {
     addHTML += '
blah blah
';
 else {
     addHTML += '
blah blah blah
'
 }

The if/else statement works as shown above (it does add the HTML line if it matches the user's input).
The gauge also works by itself (if I include

 in my HTML doc before running.
The issue I'm having is that I can't add the gauge directly from the if/else statement above. I've tried a variety of ways with no luck, such as:
addHTML += '
' + gaugeProgress(0.5) + '
';
and
addHTML += '

';
addHTML += document.getElementById("chart-gauge").innerHTML = gaugeProgress(0.5);

Any help would be much appreciated!

redpajama_set_name: RedPajamaStackExchange


We offer a unique selection of modern dog and cat bowls and feeders. These modern diners come in a variety of colors, sizes and styles.
We carry designer floor models, as well as elevated and wall-mounted dog bowls and cat bowls which are a healthier option than floor pet feeders as they allow your pet to eat without having to crouch their head down, alleviating undue stress and giving them better posture.
We also carry smart bowls and automatic pet feeders. These high-tech pet feeders personalize your dog's meals and feeding schedule based on his or her details and requirements. They also weigh food to assure the right serving sizes, alert you of changes in your dog's eating and drinking habits making you aware of any health concerns, automatically reorder food and more!
And not only will your dog or cat love their new contemporary bowl but you will also as these stylish designs will add a nice modern touch to your kitchen. Let your dog or cat dine in style with an ultra modern pet bowl.


text:
With $36M series B, Finch goes full speed ahead in microbiome therapy
Mar 1, 2018 9:56am
Finch merged with fellow microbiome biotech, Crestovo, in October, picking up the C. difficile treatment CP101 in the process. (Lois S. Wiggs/CDC)
Finch Therapeutics snagged another $36 million in funding, boosting its capital raised to $77 million and enabling it to carry its C. difficile treatment, CP101, through phase 2.
The Somerville, Massachusetts-based startup picked up CP101, what it calls a "full-spectrum microbiota product," in its October merger with Crestovo. At the time, Crestovo's pipeline was further ahead, having started a phase 2 trial of CP101 in 240 patients with C. diff infections.
In addition to supporting Finch's ongoing phase 2 efforts for CP101, the new funding will also advance its earlier-stage pipeline. This includes pushing forward FIN-524, a candidate composed of cultured bacterial strains for treating inflammatory bowel disease.
Six months before Finch tied the knot with Crestovo, it inked a pact with Takeda that saw the Japanese pharma hand over $10 million for the worldwide rights to FIN-524, as well as the rights to follow-on products for IBD. It was Takeda's second microbiome deal within a week—the company tapped NuBiyota and its microbiome platform to develop treatments for gastrointestinal diseases.
"We look forward to continued progress in PRISM 3, our ongoing Phase 2 study of CP101, an orally delivered Full-Spectrum Microbiota product being developed for recurrent C. difficile infections," said Mark Smith, CEO of Finch Therapeutics.
"We are also excited to advance our pipeline of therapeutic candidates into the clinic both through sponsored programs and in collaboration with Takeda and our academic partners as we work to realize the exciting potential of the human microbiome."
Clostridium difficile (C. diff) inflammatory bowel disease microbiome Finch Therapeutics


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Mary Robinson (née Darby; 27 November 1757 – 26 December 1800) was an English actress, poet, dramatist, novelist, and celebrity figure. She lived in England, in the cities of Bristol and London; she also lived in France and Germany for a time. She enjoyed poetry from the age of seven and started working, first as a teacher and then as actress, from the age of fourteen. She wrote many plays, poems and novels. She was a celebrity, gossiped about in newspapers, famous for her acting and writing. During her lifetime she was known as "the English Sappho". She earned her nickname "Perdita" for her role as Perdita (heroine of Shakespeare's The Winter's Tale) in 1779. She was the first public mistress of King George IV while he was still Prince of Wales.

Biography

Early life
Robinson was born in Bristol, England to Nicholas Darby, a naval captain, and her wife Hester (née Vanacott) who had married at Donyatt, Somerset, in 1749, and was baptised 'Polle(y)' ("Spelt 'Polle' in the official register and 'Polly' in the Bishop's Transcript") at St Augustine's Church, Bristol, 19 July 1758, the entry noting that she was born 27 November 1756. In her memoirs, Robinson gives her birth in 1758, but the year 1757 seems more likely according to recently published research (see appendix to Byrne, 2005). Her father deserted her mother and took a mistress when Robinson was still a child. The family hoped for a reconciliation, but Captain Darby made it clear that this was not going to happen. Without the support of her husband, Hester Darby supported herself and the five children born of the marriage by starting a school for young girls in Little Chelsea, London, (where Robinson taught by her 14th birthday). However, during one of his brief returns to the family, Captain Darby had the school closed (which he was entitled to do by English law). Darby died in the Russian naval service in 1785. Robinson, who at one point attended a school run by the social reformer Hannah More, came to the attention of actor David Garrick.

Marriage
Hester Darby encouraged her daughter to accept the proposal of an articled clerk, Thomas Robinson, who claimed to have an inheritance. Mary was against this idea; however, after falling ill and watching him take care of her and her younger brother, she felt that she owed him, and she did not want to disappoint her mother who was pushing for the engagement. After the early marriage, Robinson discovered her husband did not have an inheritance. He continued to live an elaborate lifestyle, however, and made no effort to hide multiple affairs. Subsequently, Mary supported their family. After her husband squandered their money, the couple fled to Talgarth, Breconshire (where Robinson's only daughter, Mary Elizabeth, was born in November). Here they lived in a fairly large estate, called Tregunter Park. Eventually her husband was imprisoned for debt in the Fleet Prison where she lived with him for many months. While it was common for the wives of prisoners to live with their husbands while indebted, children were usually sent to live with relatives to keep them away from the dangers of prison. However, Robinson was deeply devoted to her daughter Maria, and when her husband was imprisoned, Robinson brought the 6-month-old baby with her.

It was in the Fleet Prison that Robinson's literary career really began, as she found that she could publish poetry to earn money, and to give her an escape from the harsh reality that had become her life. Her first book, Poems By Mrs. Robinson, was published in 1775 by C. Parker. Additionally, Robinson's husband was offered work in the form of copying legal documents so he could try to pay back some of his debts, but he refused to do anything. Robinson, in an effort to keep the family together and to get back to normal life outside of prison, took the job instead, collecting the pay that her husband neglected to earn. During this time, Mary Robinson found a patron in Georgiana Cavendish, Duchess of Devonshire, who sponsored the publication of Robinson's second volume of poems, Captivity.

Theatre

After her husband obtained his release from prison, Robinson decided to return to the theatre. She launched her acting career and took to the stage playing Juliet at Drury Lane Theatre in December 1776. Robinson was best known for her facility with the 'breeches parts', and her performances as Viola in William Shakespeare'sTwelfth Night and Rosalind in As You Like It won her extensive praise. But she gained popularity with playing in Florizel and Perdita, an adaptation of Shakespeare, with the role of Perdita (heroine of The Winter's Tale) in 1779. It was during this performance that she attracted the notice of the young Prince of Wales, later King George IV of the United Kingdom. He offered her twenty thousand pounds to become his mistress. During this time, the very young Emma, Lady Hamilton sometimes worked as her maid and dresser at the theatre.

With her new social prominence, Robinson became a trend-setter in London, introducing a loose, flowing muslin style of gown based upon Grecian statuary that became known as the Perdita. It took Robinson a considerable amount of time to decide to leave her husband for the Prince, as she did not want to be seen by the public as that type of woman. Throughout much of her life she struggled to live in the public eye and also to stay true to the values in which she believed. She eventually gave in to her desires to be with a man who she thought would treat her better than Mr Robinson. However the Prince ended the affair in 1781, refusing to pay the promised sum. "Perdita" Robinson was left to support herself through an annuity promised by the Crown (but rarely paid), in return for some letters written by the Prince, and through her writings. After her affair with the young Prince of Wales she became famous for her rides in her extravagant carriages and her celebrity–like perception by the public.

Later life and death

Mary Robinson, who now lived separately from her husband, went on to have several love affairs, most notably with Banastre Tarleton, a soldier who had recently distinguished himself fighting in the American War of Independence. Prior to their relationship, Robinson had been having an affair with a man named Lord Malden. According to one account, Malden and Tarleton were betting men, and Malden was so confident in Robinson's loyalty to him, and believed that no man could ever take her from him. As such, he made a bet of a thousand guineas that none of the men in his circle could seduce her. Unfortunately for Malden, Tarleton accepted the bet and swooped in to not only seduce Robinson, but establish a relationship that would last the next 15 years. This relationship, though rumoured to have started on a bet, saw Tarleton's rise in military rank and his concomitant political successes, Mary's own various illnesses, financial vicissitudes and the efforts of Tarleton's own family to end the relationship. They had no children, although Robinson had a miscarriage. However, in the end, Tarleton married Susan Bertie, an heiress and an illegitimate daughter of the young 4th Duke of Ancaster, and niece of his sisters Lady Willoughby de Eresby and Lady Cholmondeley. In 1783, Robinson suffered a mysterious illness that left her partially paralysed. Biographer Paula Byrne speculates that a streptococcal infection resulting from a miscarriage led to a severe rheumatic fever that left her disabled for the rest of her life.

From the late 1780s, Robinson became distinguished for her poetry and was called "the English Sappho". In addition to poems, she wrote eight novels, three plays, feminist treatises, and an autobiographical manuscript that was incomplete at the time of her death. Like her contemporary Mary Wollstonecraft, she championed the rights of women and was an ardent supporter of the French Revolution. She died in poverty at Englefield Cottage, Englefield Green, Surrey, 26 December 1800, aged 44, having survived several years of ill health, and was survived by her daughter, Maria Elizabeth (1774-1818), who was also a published novelist. Administration of her estate was granted to her husband Thomas Robinson from whom she had long been separated and who in 1803 inherited a substantial estate from his half-brother William. One of Robinson's dying wishes was to see the rest of her works published. She tasked her daughter, Maria Robinson, with publishing most of these works. She also placed her Memoirs in the care of her daughter, insisting that she publish the work. Maria Robinson published Memoirs just a few months later.

Portraits
During her lifetime, Robinson also enjoyed the distinction of having her image captured by the most notable artists of the period. The earliest known, drawn by James Roberts II, depicts "Mrs. Robinson in the Character of Amanda" from Cibber's Love's Last Shift in 1777. In 1781, Thomas Gainsborough produced an oil sketch, Mrs. Mary Robinson 'Perdita', and an untitled study. That year, George Romney also painted Mrs. Mary Robinson and John Keyse Sherwin printed an untitled portrait. Joshua Reynolds sketched a study for what became Portrait of a Lady in 1782, and in 1784, he finished Mrs Robinson as Contemplation for which he also sketched a study. George Dance the Younger sketched a later portrait in 1793.

Literature

In 1792 Robinson published her most popular novel which was a Gothic novel titled, Vancenza; or The Dangers of Credulity. The books were "sold out by lunch time on the first day and five more editions quickly followed, making it one of the top-selling novels in the latter part of the eighteenth century." It did not receive either critical or popular acclaim. In 1794 she wrote The Widow; or, A Picture of Modern Times which portrayed themes of manners in the fashionable world. Since Robinson was a fashion icon and very much involved in the fashion world the novel did not get a lot of favourable reception in 1794 as it might have now. In 1796 she wrote Angelina: A Novel. It cost more money than it brought in. Through this novel, she offers her thoughts on the afterlife of her literary career.

There has been an increase in scholarly attention to Robinson's literary output in recent years. While most of the early literature written about Robinson focused on her sexuality, emphasising her affairs and fashions, she also spoke out about woman's place in the literary world, for which she began to receive the attention of feminists and literary scholars in the 1990s. Robinson recognised that, "women writers were deeply ambivalent about the myths of authorship their male counterparts had created" and as a result she sought to elevate woman's place in the literary world by recognising women writers in her own work. In A Letter to the Women of England, Robinson includes an entire page dedicated to English women writers to support her notion that they were just as capable as men of being successful in the literary world. These ideas have continued to keep Mary Robinson relevant in literary discussions today. In addition to maintaining literary and cultural notability, she has re-attained a degree of celebrity in recent years when several biographies of her appeared, including one by Paula Byrne entitled Perdita: The Literary, Theatrical, and Scandalous Life of Mary Robinson that became a top-ten best-seller after being selected for the Richard & Judy Book Club.

An eight-volume scholarly edition of Robinson's complete works was published in 2009–2010. In 2011, Daniel Robinson (no relation), editor of the poetry for the edition, published the first scholarly monograph to focus exclusively on her literary achievement--The Poetry of Mary Robinson: Form and Fame. A second monograph on Robinson's literary career, Mary Robinson and the Genesis of Romanticism: Literary Dialogues and Debts, 1784-1821, by Ashley Cross, appeared in 2016. Although, Robinson's novels were not as successful as she hoped, she had a talent for her poetry. Her ability to produce poetry can be seen furthermore in her poems titled "Sappho and Phaeon". Since the press had given her the name "The English Sappho", a clear relationship can be drawn between these poems and her literary name. The poems are love poems and many scholars have come to the conclusion that they represent her affairs with the Prince of Wales. Mary Darby Robinson was not only praised in literary circles for her poetry but also for her works written in prose. The two best known examples are "A Letter to the Women of England" (1798) and "The Natural Daughter" (1799). Both her works are dealing with the role of women during the Romantic Era. Mary Robinson as much as Mary Wollenstonecraft tried to put the focus on how inferior women were treated in comparison to men. The discrepancy can be seen in both of her works. "The Natural Daughter" can be seen as an autobiography of Mary Robinson. The characters are in many ways patterns of her own life and the stages of her life. All the characters are symbols of her own coming of age or people she met in her life.

Poetry

From the late 1780s, Robinson, striving to separate herself from her past scandals, and life as a theatre actress, turned to writing as a full-time career. Robinson, disregarding her previous associations with the nickname "Perdita", meaning "lost one", soon became distinguished for her poetry and was reclassified as "the English Sappho" by the English public. During her 25-year writing career, from 1775 until her premature death in 1800, Robinson produced an immense body of work. In addition to eight collections of poems, Robinson wrote eight novels, three plays, feminist treatises, and an autobiographical manuscript that was incomplete at the time of her death.

Poems by Mrs. Robinson, was published by C. Parker, in London, in 1775. "Poems" consisted of "twenty-six ballads, odes, and elegies" that "echo traditional values, praising values such as charity, sincerity, and innocence, particularly in a woman". Robinson's husband, Thomas Robinson was imprisoned at the King's Bench Prison for fifteen months for the gambling debts he acquired. Robinson originally intended for the profits made from this collection to help pay off his debts. But the publication of Poems could not prevent his imprisonment. Robinson lived for nine months and three weeks with Thomas and their baby within the squalor of prison.

Motivated by the months she spent in prison, Robinson wrote Captivity; a Poem and Celadon and Lydia, a Tale, published by T. Becket, in London, in 1777. This collection "described the horrors of captivity and painted a sympathetic picture of the 'wretch' and the 'guiltless partners of his poignant woes'...The poem ends admonishing people to open their hearts and to pity the unfortunate..."

Following the publication of Captivity, Robinson established a new poetic identity for herself. Robinson let go of her Della Cruscan style when she wrote Poems by Mary Robinson, published in 1791 by J. Bell in London, and Poems by Mrs. Robinson, published in 1793 by T. Spilsbury in London. A review was written by the Gentleman's Magazine and the reviewer stated that if Robinson had been less blessed with "beauty and captivating manners","her poetical taste might have been confined in its influence". At the end of the review, "the Gentleman's Magazine describes her poetry as elegant and harmonious.

In 1795, Robinson wrote a satirical poem titled London's Summer Morning, but it was published after her death in 1800. This poem showcased Robinson's critical perspective of the infrastructure and society of London. Robinson described the busy and loud sounds of the industrialised city in the morning. She employed characters such as the chimney-boy, and ruddy housemaid to make a heavy critique on the way English society treated children as both innocent and fragile creatures.

In 1796, Robinson argued for women's rationality, their right to education and illustrated ideas of free will, suicide, rationalisation, empiricism and relationship to sensibility in Sappho and Phaon: In a Series of Legitimate Sonnets.

During the 1790s, Robinson was highly inspired by feminism and desired to spread her liberal sentiments through her writing. She was an ardent admirer of Mary Wollstonecraft, an established and influential feminist writer of the period. But to Robinson's surprise, her intense feelings were not reciprocated by Wollstonecraft. While Robinson expected a strong friendship between the two of them to flourish, Wollstonecraft "found Robinson herself considerably less appealing than the title character of Angelina". In 1796, Wollstonecraft wrote an extremely harsh review of Robinson's work in the Analytical Review. It was this critique that was not critical, or well thought out. Instead, Wollstonecraft's review of Robinson proved to be relatively shallow and pointed at her jealousy of Robinson's comparable freedom. Wollstonecraft had the potential to spend more of her own time writing, instead of having to entertain her husband, William Goodwin. Robinson's "Letter to the Women of England against Mental Subordination" is still powerful reading. Robinson reiterates the rights women have to live by sexual passion.

Lastly, in 1800, after years of failing health and decline into financial ruin, Robinson wrote her last piece of literature during her lifetime: a series of poems titled the Lyrical Tales, published by Longman & Rees, in London. This poetry collection explored themes of domestic violence, misogyny, violence against destitute characters, and political oppression. "Robinson's last work pleads for a recognition of the moral and rational worth of women: 'Let me ask this plain and rational question-- is not woman a human being, gifted with all the feelings that inhabit the bosom of man?". Robinson's main objective was to respond to Lyrical Ballads written by authors Wordsworth and Coleridge; who were not as well known at the time. Although it was not as highly praised as Mary Wollstonecraft's "A Vindication of the Rights of Woman", published in 1792, Lyrical Tales provides a "powerful critique of the division of duties and privileges between the sexes. It places Robinson firmly on the side of the 'feminist' thinkers or 'modern' philosophers of the 1790s, as one of the strong defenders of her sex".

Criticism and reception
Robinson was known as a sexualised celebrity, but she was a very talented writer. Robinson did not receive recognition for her work until much later because of "strict attitudes led to a rejection of the literary work of such a notorious woman." She became a lesson to young girls about the dangers of promiscuity, and pleasure seeking. She was named by her friend Samuel Taylor Coleridge "as a woman of undoubted genius." The collection of Poems published in 1791 had a "subscription list of 600 people was headed by His Royal Highness, George, Prince of Wales, and included many other members of the nobility. Some people subscribed because of her writing, some because of her notoriety, and some perhaps out of pity for the former actress, now crippled and ill. Reviews were generally kind, and noted traces in her poems of a sensibility that would later be termed Romanticism." Twenty years after her death the Poetical Works of The Late Mrs. Robinson was published in 1824, which speaks to her ongoing popularity. Robinson's second novel The Widow, and in her controversial comedy Nobody: A Comedy in Two Acts both of which, according to newspaper reports, offended fashionable women. Needless to say, Robinson's playwright career was short-lived after all the bad reviews of her play. The upper class interpreted her satire as mockery on female gambling and it was an attack on moral legitimacy of the Whig elite. The upper class interpretation of Nobody reveals a great deal about the social and political anxieties during the revolutionary era.

Robinson's poems were popular, especially after she produced a variety of poems whilst working at the newspaper The Morning Post. The poetry columns had a double agenda of pleasing a substantial and diverse audience and shaping them into a select group of elite readers eager to buy and consume books. The public adored the novel Vancenza; or The Dangers of Credulity, but the critical reception was mixed. Furthermore, a biographer Paula Byrne recently dismissed it as a "product of the vogue for Gothic fiction [that] now seems overblown to the point of absurdity." Although Robinson's poetry was more popular than her other works, the most lucrative "was her prose. The money helped to support herself, her mother and daughter, and often Banastre Tarleton. Novels such as Vancenza (1792), The Widow (1794), Angelina (1796), and Walsingham (1797) went through multiple editions and were often translated into French and German. They owed part of their popularity to their suspected autobiographical elements. Even when her characters were placed in scenes of gothic horror, their views could be related to the experiences of their author."

Mary Robinson was one of the first female celebrities of the modern era. She was dubbed as scandalous, but on the other hand educated and able to be partially independent from her husband. She was one of the first women to enter the sphere of writing, and to be successful there. Scholars often argue that she used her celebrity status only in her own advantage, but it is to be noted how much she contributed to the awareness of early feminism. She tried to elaborate the ideas of equality for women in England during the late 18th century. Nevertheless, many contemporary women were not amused with how she exposed herself to the public and ostracised her. They did not want to be associated with her, since they feared to receive a bad reputation sympathising with Mary Robinson.

Works

Poetry

 Poems by Mrs. Robinson (London: C. Parker, 1775) Digital Edition
 Captivity, a Poem and Celadon and Lydia, a Tale. Dedicated, by Permission, to Her Grace the Duchess of Devonshire. (London: T. Becket, 1777)
 Ainsi va le Monde, a Poem. Inscribed to Robert Merry, Esq. A.M. [Laura Maria] (London: John Bell, 1790) Digital Edition
 Poems by Mrs. M. Robinson (London: J. Bell, 1791) Digital Edition
 The Beauties of Mrs. Robinson (London: H. D. Symonds, 1791)
 Monody to the Memory of Sir Joshua Reynolds, Late President of the Royal Academy, &c. &c. &c. (London: J. Bell, 1792)
 Ode to the Harp of the Late Accomplished and Amiable Louisa Hanway (London: John Bell, 1793)
 Modern Manners, a Poem. In Two Cantos. By Horace Juvenal (London: Printed for the Author, 1793)
 Sight, the Cavern of Woe, and Solitude. Poems (London: T. Spilsbury and Son, 1793)
 Monody to the Memory of the Late Queen of France (London: T. Spilsbury and Son, 1793)
 Poems by Mrs. M. Robinson. Volume the Second (London: T. Spilsbury and Son, 1793)
 Poems, by Mrs. Mary Robinson. A New Edition (London: T. Spilsbury, 1795)
 Sappho and Phaon. In a Series of Legitimate Sonnets, with Thoughts on Poetical Subjects, and Anecdotes of the Grecian Poetess (London: For the Author, 1796) Digital Edition
 Lyrical Tales, by Mrs. Mary Robinson (London: T. N. Longman and O. Rees, 1800) Digital Edition
 The Mistletoe. --- A Christmas Tale [Laura Maria] (London: Laurie & Whittle, 1800)

Novels
 Vancenza; or, the Dangers of Credulity. In Two Volumes (London: Printed for the Authoress, 1792)
 The Widow, or a Picture of Modern Times. A Novel, in a Series of Letters, in Two Volumes (London: Hookham and Carpenter, 1794)
 Angelina; a Novel, in Three Volumes (London: Printed for the Author, 1796)
 Hubert de Sevrac, a Romance, of the Eighteenth Century (London: Printed for the Author, 1796)
 Walsingham; or, the Pupil of Nature. A Domestic Story (London: T. N. Longman, 1797)
 The False Friend: a Domestic Story (London: T. N. Longman and O. Rees, 1799)
 Natural Daughter. With Portraits of the Leadenhead Family]. A Novel (London: T. N. Longman and O. Rees, 1799)

Dramas
 The Lucky Escape, A Comic Opera (performed on 23 April 1778 at the Theatre Royal, Drury Lane)
 The Songs, Chorusses, &c. in The Lucky Escape, a Comic Opera, as Performed at the Theatre-Royal, in Drury-Lane (London: Printed for the Author, 1778)
 Kate of Aberdeen (a comic opera withdrawn in 1793 and never staged)
 Nobody. A Comedy in Two Acts (performed on 27 Nov. 1794 at the Theatre Royal, Drury Lane) Digital Edition
 The Sicilian Lover. A Tragedy. In Five Acts (London: Printed for the Author, 1796)

Political Treatises

 Impartial Reflections on the Present Situation of the Queen of France; by A Friend to Humanity (London: John Bell, 1791)
 A Letter to the Women of England, on the Injustice of Mental Subordination. With Anecdotes. By Anne Frances Randall] (London: T. N. Longman and O. Rees, 1799) Digital Edition
 Thoughts on the Condition of Women, and on the Injustice of Mental Subordination (London: T. N. Longman and O. Rees, 1799)

Essays

 "The Sylphid. No. I," Morning Post and Gazetteer 29 Oct. 1799: 2 (also printed in Memoirs 3: 3–8)
 "The Sylphid. No. II," Morning Post and Gazetteer 7 Nov. 1799: 2 (also printed in Memoirs 3: 8–16)
 "The Sylphid. No. III," Morning Post and Gazetteer 16 Nov. 1799: 3 (also printed in Memoirs 3: 17–21)
 "The Sylphid. No. IV," Morning Post and Gazetteer 23 Nov. 1799: 2 (edited version printed in Memoirs 3: 21–26)
 "The Sylphid. No. V," Morning Post and Gazetteer 27 Nov. 1799: 2 (also printed in Memoirs 3: 27–31)
 "The Sylphid. No. VI," Morning Post and Gazetteer 7 Dec. 1799: 2 (edited version printed in Memoirs 3: 31–35)
 "The Sylphid. No. VII," Morning Post and Gazetteer 19 Dec. 1799: 2 (also printed in Memoirs 3: 35–40)
 "The Sylphid. No. VIII," Morning Post and Gazetteer 24 Dec. 1799: 2 (also printed in Memoirs 3: 41–45)
 "The Sylphid. No. IX," Morning Post and Gazetteer 2 Jan. 1800: 3 (also printed as No. XIV in Memoirs 3: 74–80)
 "To the Sylphid," Morning Post and Gazetteer 4 Jan. 1800: 3 (also printed as No. IX in Memoirs 3: 46–50)
 "The Sylphid. No. X," Morning Post and Gazetteer 7 Jan. 1800: 3 (also printed in Memoirs 3: 51–57)
 "The Sylphid. No. XI," Morning Post and Gazetteer 11 Jan. 1800: 2 (also printed in Memoirs 3: 58–63)
 "The Sylphid. No. XII," Morning Post and Gazetteer 31 Jan. 1800: 2 (edited version printed in Memoirs 3: 63–68)
 "The Sylphid. No. XIII," Memoirs 3: 68-73 (no extant copy of Morning Post exists)
 "Present State of the Manners, Society, &c. &c. of the Metropolis of England," Monthly Magazine 10 (Aug. 1800): 35–38.
 "Present State of the Manners, Society, &c. &c. of the Metropolis of England," Monthly Magazine 10 (Sept. 1800): 138-40
 "Present State of the Manners, Society, &c. &c. of the Metropolis of England," Monthly Magazine 10 (Oct. 1800): 218-22
 "Present State of the Manners, Society, &c. &c. of the Metropolis of England," Monthly Magazine 10 (Oct. 1800): 305-06

Translation

 Picture of Palermo by Dr. Hager translated from the German by Mrs. Mary Robinson (London: R. Phillips, 1800)

Biographical Sketches

 "Anecdotes of Eminent Persons: Memoirs of the Late Duc de Biron," Monthly Magazine 9 (Feb.1800): 43-46
 "Anecdotes of Eminent Persons: Account of Rev. John Parkhurst," Monthly Magazine 9 (July 1800): 560-61
 "Anecdotes of Eminent Persons: Account of Bishop Parkhurst," Monthly Magazine 9 (July 1800): 561
 "Anecdotes of Eminent Persons: Additional Anecdotes of Philip Egalité Late Duke of Orleans," Monthly Magazine 10 (Aug. 1800): 39-40
 "Anecdotes of Eminent Persons: Anecdotes of the Late Queen of France," Monthly Magazine 10 (Aug. 1800): 40-41

Posthumous Publications
 "Mr. Robert Ker Porter." Public Characters of 1800-1801 (London: R. Phillips, 1801)
 Memoirs of the Late Mrs. Robinson, Written by Herself with Some Posthumous Pieces. In Four Volumes (London: R. Phillips, 1801)
 "Jasper. A Fragment," Memoirs of the Late Mrs. Robinson, Vol. 3 (London: R. Phillips, 1801)
 "The Savage of Aveyron," Memoirs of the Late Mrs. Robinson, Vol. 3 (London: R. Phillips, 1801)
 "The Progress of Liberty," Memoirs of the Late Mrs. Robinson, Vol. 4 (London: R. Phillips, 1801)
 The Poetical Works of the Late Mrs. Mary Robinson: Including Many Pieces Never Before Published. In Three Volumes (London: Richard Phillips, 1806)

Publications about Robinson and Her Work

Biographies (Ordered by Date of Publication)

 "A Tribute of Respect to the Memory of the Late Mrs. Robinson, in the Form of a Monumental Inscription." Weekly Entertainer 37 (June 1801): 517.
 "Mrs. Robinson." Public Characters of 1800-1801. London: R. Phillips, 1801. 327–37.
 Jones, Stephen. "Robinson (Mary)." A New Biographical Dictionary: Containing a Brief Account of the Life and Writings of the Most Eminent Persons and Remarkable Characters in Every Age and Nation. 5th ed. London: Longman, Hurst, Rees and Orne; J. Wallis; W. Peacock and Sons; J. Harris; Scatcherd and Letterman; Vernor and Hood; and J. Walker, 1805. N. pag.
 "Biographical Sketch of Mrs. Mary Robinson." The Hibernia Magazine, and Dublin Monthly Panorama 3 (1811): 25–28.

 Craven, Mary. Famous Beauties of Two Reigns; Being an Account of Some Fair Women of Stuart & Georgian Times. London: E. Nash, 1906.
 Fyvie, John. Comedy Queens of the Georgian Era. New York: E.P. Dutton, 1907.
 Makower, Stanley. Perdita: A Romance in Biography. London: Hutchinson, 1908.

 Barrington, E. [Lily Adams Beck]. The Exquisite Perdita. New York: Dodd, Mead and Company, 1926.
 Benjamin, Lewis S. More Stage Favorites of the Eighteenth Century. Freeport, NY: Books for Libraries Press, Inc, 1929.
 Mendenhall, John C. "Mary Robinson (1758-1800)." University of Pennsylvania Library Chronicle 4 (1936): 2–10.
 Steen, Marguerite. The Lost One, a Biography of Mary (Perdita) Robinson. London: Methuen & Co., 1937.
 Bass, Robert D. The Green Dragoon: The Lives of Banastre Tarleton and Mary Robinson. New York: Henry Hold and Company, 1957.
 Ty, Eleanor. "Mary Robinson." In British Reform Writers, 1789-1832, edited by Gary Kelly, 297–305. Detroit: Thomson Gale, 1995.
 Levy, Martin J. "Mrs. Robinson." The Mistresses of King George IV. London: P. Owen, 1996. 13–43.
 Meyers, Kate Beaird. "Mary Darby Robinson ('Perdita')." An Encyclopedia of British Women Writers. Eds. Paul and June Schleuter. Rev. and Expanded. New Brunswick: Rutgers UP, 1998. 391-92.
 Schlueter, Paul, and June Schlueter. "Mary Robinson." An Encyclopedia of British Women Writers. New Brunswick: Rutgers UP, 1998.
 Pascoe, Judith, ed. "Introduction." Mary Robinson: Selected Poems. Peterborough, ON: Broadview Press, 2000.
 Binhammer, Katherine. "Mary Darby Robinson (1758–1800)." Female Spectator 4.3 (2000): 2–4.
 Byrne, Paula. Perdita: The Literary, Theatrical, and Scandalous Life of Mary Robinson. New York: Random House, 2004.
 Davenport, Hester. The Prince's Mistress: Perdita, a Life of Mary Robinson. Stroud: Sutton Publishing, 2004.
 Denlinger, Elizabeth Campbell. Before Victoria: Extraordinary Women of the British Romantic Era. New York: New York Public Library: Columbia University Press, 2005.
 Gristwood, Sarah. Perdita: Royal Mistress, Writer, Romantic. London: Bantam, 2005.
 Gristwood, Sarah. Bird of Paradise: The Colourful Career of the First Mrs Robinson. London: Bantam, 2007.
 Brewer, William D., ed. The Works of Mary Robinson. 8 vols. Pickering & Chatto, 2009–2010.
 Davenport, Hester, Ed. "'Sketch of Mrs Robinson's Life by Herself.'" In The Works of Mary Robinson, edited by William D. Brewer, 7: 333-35. London: Pickering and Chatto, 2010.
 Perry, Gill, Joseph Roach, and Shearer West. "Mary Robinson: Born in 1756/8 – Died in 1800." In The First Actresses: Nell Gwyn to Sarah Siddons. Ann Arbor: University of Michigan Press, 2011. 55.

Selected Resources on Robinson and Her Work

 Barron, Phillip. "'Who Has Not Wak'd': Mary Robinson and Cartesian Poetry." Philosophy and Literature 41.2 (2017): 392–399.
 Brewer, William D., ed. The Works of Mary Robinson. 8 vols. Pickering & Chatto, 2009–2010.
 Cross, Ashley. Mary Robinson and the Genesis of Romanticism: Literary Dialogues and Debts, 1784-1821. London: Routledge, 2016.
 Gamer, Michael, and Terry F. Robinson. "Mary Robinson and the Dramatic Art of the Comeback." Studies in Romanticism 48.2 (Summer 2009): 219–256.
 Ledoux, Ellen Malenas. "Florizel and Perdita Affair, 1779–80." BRANCH: Britain, Representation and Nineteenth-Century History. Ed. Dino Franco Felluga. Extension of Romanticism and Victorianism on the Net. Web. 2 June 2013.
 Pascoe, Judith. Mary Robinson: Selected Poems. Peterborough, ON: Broadview Press, 1999.
 Robinson, Daniel. The Poetry of Mary Robinson: Form and Fame. New York: Palgrave Macmillan, 2011.
 Robinson, Terry F. "Introduction." Nobody. By Mary Robinson. Romantic Circles. Web. March 2013.
 Robinson, Terry F. "Becoming Somebody: Refashioning the Body Politic in Mary Robinson's Nobody." Studies in Romanticism 55 (Summer 2016): 143–184.

Fictional Works about Robinson

 Plaidy, Jean. Perdita's Prince. 1969.
 Elyot, Amanda. All For Love: The Scandalous Life and Times of Royal Mistress Mary Robinson. A Novel. 2008.
 Lightfoot, Freda. Lady of Passion: The Story of Mary Robinson. 2013.

Notes

References
Binhammer, Katherine. 'Thinking Gender with Sexuality in 1790s Feminist Thought.' Feminist Studies 28.3 (2002): 667–90.
Byrne, Paula (2005). Perdita: The Life of Mary Robinson. London: HarperCollins and New York: Random House.
Gristwood, Sarah (2005). Perdita: royal mistress, writer, romantic. London: Bantam.

Robinson, Mary, and Mary Elizabeth Robinson (1801). Memoirs of the Late Mrs. Robinson. London: Printed by Wilkes and Taylor for R. Phillips.
Mary Darby Robinson biography
Mary Robinson memoirs

External links

 Mary Robinson at the Eighteenth-Century Poetry Archive (ECPA)

 Portrait of Mary Robinson by Gainsborough The Guardian, 26 August 2000
Mary Robinson profile Contemporary obituaries and death notices Tarleton site

English women poets
Mary
Mistresses of George IV of the United Kingdom
1757 births
1800 deaths
Actresses from Bristol
18th-century British women writers
English women novelists
Writers of the Romantic era
English stage actresses
English courtesans
English feminists
18th-century English actresses
English women dramatists and playwrights
18th-century English novelists
18th-century English poets
18th-century British dramatists and playwrights

redpajama_set_name: RedPajamaWikipedia


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There was a time when th design was on someone's drawing board and this would have been a small tweak. (I see references to this being Philip Labre's 1928 design, but the patent shows a flat ground pin.) At least Denmark got it right.


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I don't understand how you can open a drawing that was done previously, work on it for 5 minutes, forget to save it and not be able to reopen the original DWG file. Where did it disappear to? Did you search your entire hard drive? You're not on a network are you? Something seems amiss.
I remember that there is an issue with saving file while working in Block Editor. This could be it.
If this is the case, then the only hope is the backup file or autosave. If there is no backup, then he need to redraw it from scratch.
Yes, I've encountered that issue a few times before.
The file size ,currently, is 62.3KB.
Now we are getting some useful information.
It is unlikely there is anything salvagable in that file, but you might attach it here as requested previously for others to check.
The problem is,that I thought I had saved the file in my normal manner,but in the flap at the time I have obviously not done so.
I have located a .BAK file but that is the same size and I cannot open it anyway.
I do find meaningless and trivial not particularly helpful in this context-----but then you don't have the problem.
I will thank you for your interest----i have brought some amusement into your ivory towers and I shall continue to redraw the file.
I distinctly recall telling you what to do with a BAK file (i.e. - renaming). Maybe you skipped reading that post.
Hope the OP comes back, I'm interested in how this one plays out.
I hope the OP figures out that he probably only lost 5 minutes of work. This is just a classic example of not really knowing your CAD system and how it backs up your work. Not picking on the OP but any good CAD user should know this.
If that is the case, it should be cured with RECOVER.
Supposed to be updates to fix the "save from block editor" problem.
I want to make sure you understand the meaning of my reference to "floaters".
Occasionally you might accidently create some little piece of geometry far far away from the main geometry.
Then when you do a zoom all because AutoCAD has to back out so far to show everything - the geometry appears so small on the screen that it actually disappears. The sudden reaction is "all is lost". But it isn't really - simply need to find the floater(s) and delete or move closer the main geometry.
Everyone here has been through the same thing you experienced and learned these lessons the hard way.
I am certain there is nothing floating.
After many years on a drawing board,I am not confident with CAD or computers-----How do I attach the file to this message!!!!!
Under the Quick Reply text input field, click "Go Advanced," then "Manage Attachments."
I concur that there is no need to feel offended here. Everyone has had these moments of dread and panic, and everyone has lost drawings and data; consequently, everyone here feels for you. They just have not yet given up hope, because recovery may be very near and much easier than you think. I do admit--and I apologize for not being able to help it--that I was a bit amused at the ludicrous accusations, especially when so many are earnestly trying to help…for free!
If you are able to figure out how to post the drawing, be sure to post the .bak file as well, just in case it is somehow different.
As for floaters, how can you be so sure? You are too inexperienced at this to say this so confidently. Floaters can easily be created accidentally without one's realizing it. This is especially true when using COPY, as your original item is left intact. All you have to do is accidentally treat the base point as the displacement by hitting Enter prematurely. You may be wondering why nothing happened. While it may look like nothing happened, there is now a perfect copy floating way out there in space, just like you told it to do, accidentally of course.
Less likely things could hide everything from you, e.g., all Layers OFF or all Frozen. The Block Editor scenario mentioned does not seem likely, as you said you did not Save.
In many cases, one way to tell if you have anything in your drawing would be to enter the command SELECT and then the option ALL. If it reports 0 objects found, then you may indeed have an empty drawing. But it sounds like you do not, so why not give it a try just to see? Be sure to tell us what you find.
Looks blank to me. So now it is time to look at the .bak file as well as the .sv$ file (if there is one for this file).
I only see one layer in the drawing, is that correct?
I find the time report rather interesting. See attachment.
What I mean is, that drawing has only been opened for edit for about an hour and twenty minutes. It is definitely not a drawing that has been opened and worked on for up to three weeks, and the drawing is absolutely empty. I have a feeling the OP may have saved the default Drawing1.dwg over the original drawing somehow. this would probably render the .bak file empty as well.
You could be on to something there---I dimly recall Drawing1.dwg surfacing during the the shutdown panic.
I would like to thank everyone who has shown an interest---I've given up on any recovery possibility and I'm well on the path to recreation.
I think you said AutoCAD was set up to create BAK files. Did you find where the files were being saved to so you know in the future where to find them if you need to?
What do you have the time span set for re: automatic saves?
I would still look for the .bak file or the .sv$ files. Something I always do when I set up a new install of AutoCAD is the create a folder on the hard drive under C: for my "automatic save file location". Create the folder and then go into AutoCAD's options and select this folder for this function.
I also am a bit paranoid about autosaves and I have mine set to 10 minutes and I have my incremental save percentage set to 0 so it does a full save.
Just some things to look at so you don't lose work. Good luck.


text:
Mora said that Locklear probably will not start, but might be used in a rotation similar to how the team handled Marcus Trufant and Leroy Hill in their first games of the season last week.
T.J. Houshmandzadeh also talked to reporters today about some of the perceptions of him being portrayed after his reaction to some frustrating plays were caught on TV against Dallas.
Houshmandzadeh again reiterated that's the way he's always been, and that he's an emotional player who expresses himself outwardly when he's frustrated, and that he's actually gotten a lot better over his playing career, including time at Oregon State and Cincinnati.
He believes part of the public reaction to his actions on the field is a feeling out process between himself and fans in Seattle.
"Obviously, it's a feeling out process, a little bit like boxers in the first three rounds of a championship fight," he said. "You kind of feel each other out. But we're losing. If we were winning, I wouldn't be a problem because I wouldn't be doing it. And it's just different. I've done it my whole career. And it's not great. I'm not like saying it's acceptable or it's OK. But I've done that, they've seen it.
"It's just emotion. I love to win. I do not like to lose. And that's just how I express myself. I mean, why would I be happy about punting the ball and walk to the sideline with a smile on my face? Why would I want it? I just outwardly expressed how I felt inside. That's it.
Houshmandzadeh also described his play as 'terrible' so far this season.
"As of right now I'm not doing anything, for whatever reason" he said. "You can print whatever you want – why is it the case. But I don't know why it is like that. But I can't do nothing about it now. It's over with, as far as the first seven games. All you can do is try and do better."
Here's the injury report.
For Seattle, Ben Obomanu (oblique) was a limited participant and is questionable. S Jordan Babineaux (hip), QB Matt Hasselbeck (rib), LB Will Herring (shoulder), T Sean Locklear (ankle) and CB Ken Lucas (neck) were all full participants and are probable.
For Detroit, FB Jerome Felton (ankle), WR Calvin Johnson (knee) and RB Kevin Smith (shoulder) were limited participants and are questionable, although Johnson likely will play and Smith might be out there as well.


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Her words on such subjects have been featured in places like The Huffington Post, Mind Body Green, Oxfam, Nature & Health Magazine, Earth Events, Inspired Coach and her zero-waste ways even popped up on Sarah Wilsons personal blog.
Emily works as a copywriter and ghostwriter, specialising in wellness, personal growth, creative and sustainability. She's worked with over 70 clients including best-selling authors, TV personalities, nutritionists, coaches, chefs, photographers and even a real life princess (sadly, it was not Pocahontas).
Whatever the writing project – she helps her clients hone their message with confidence and charm. She doesn't like cliches, sleazy sales copy or licorice. She also runs a free writing community to help more women share their stories and ideas with the world (join it here).
Emily is a certified health and life coach and is passionate about the environment. She hates plastic pollution, loves that our daily actions can make a difference and believes in using your voice to talk about things that matter. She was Social Media Manager for a grassroots campaign that saw single-use plastic bags banned in her local city (and only the second time that's ever happened in Australia).


Businesses and creditors are concerned with a wide range of risks that can arise either within the company itself or externally. Risks include management or employee fraud, personal injury claims, product liability lawsuits, natural disasters, and business failures of key suppliers.
At Odoni Partners, we spend time reviewing internal control activities and corporate policies to help you devise a strategy that reduces risk, identifies procedural gaps, and ultimately helps to implement appropriate processes. As organizations continue to seek help with protecting financial and reputational assets, our team will help you turn risk and compliance efforts into opportunities to drive sustainable business value.


By DONNA BALANCIA – Wayne Kramer and Mike Watt are among rockers who gave the Sunset Strip a shot in the arm at the Whisky A Go-Go Tuesday night.
"This is the Whisky A Go Go, where (the jam session) belongs!" cried emcee Paulie Z, who along with the rest of the "regulars," perform a high-energy show to tear the house down, week in and week out.
"This is one of the most fun nights of the week," said Jesse, who drove down from Ventura to see some of the most talented side men in the business. And a few women contributed to the success of the night as well including Debby Holiday who has become a fixture in the festivities. Holiday knows how to bring the house to its collective knees and she did not disappoint Tuesday.
Ralph Saenz, known for his wild glamrock sendup as lead singer in the big-haired, babe-bustin' musical comedy troupe Steel Panther was on hand to sing Van Halen as a burlesque artist did her thing.
"I used to be in a Van Halen tribute band," Saenz admitted. Honestly the guy can do anything and make it all funny.
Paulie Z and the house band; The Disreputable Few; Joe Retta; Micki Free; Alex Kane; Mitch Perry; Chuck Wright; Joey Malone and a host of all-stars move on and off stage during the four-hour evening. It's a free night but even if they charged, it would be well worth a ticket to see this kind of talent. One moment to note: Paulie Z. asked for a moment of silence for the recent passing of Rainbow chef Miguel Murillo.
But the first set belonged to special guests Watt and Kramer who in the late 1970s set the tone for punkers yet to come. Kramer is a founder Detroit innovators MC5 and Watt was with The Stooges.