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PDF file - 157K, Supplemental Table 1. Regulatory T cell genes included in this study (N=25). Supplemental Table 2. Regulatory T cell SNPs included in this study. Supplemental Table 3. Participating invasive epithelial ovarian cancer studies. Supplemental Table 4. Association between clinical variables and overall survival.

The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22–1.64; P = 5.7 × 10−6], rs791587 (HR, 1.36; 95% CI, 1.17–1.57; P = 6.2 × 10−5), rs2476491 (HR, = 1.40; 95% CI, 1.19–1.64; P = 5.6 × 10−5), and rs10795763 (HR, 1.35; 95% CI, 1.17–1.57; P = 7.9 × 10−5), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54–0.82; P = 9.3 × 10−5) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer. Cancer Immunol Res; 2(4); 332–40. ©2014 AACR.

Introduction: Ovarian cancer is the leading cause of death from gynecological related cancers worldwide. Most patients are diagnosed at late stages due to asymptomatic disease and lack of effective screening modalities. Additionally, in women with an ovarian mass the diagnosis of ovarian cancer can be challenging with many women having surgery only to discover a benign pathology. Liquid biopsies, including analyses of cell-free DNA (cfDNA) fragmentomes in the circulation, have shown promise for the early detection of cancer and may provide a useful avenue for detection of ovarian cancer. Methods: To evaluate cfDNA fragmentomes for detecting ovarian cancer, we assessed plasma from 507 women, including 128 with ovarian cancers comprising high grade serous, endometrioid, mucinous and clear cell subtypes, 48 with benign masses, and 223 without cancer, as well as a validation cohort of 108 women with (n=14) and without (n=94) ovarian cancers from a separate institution. We obtained cfDNA from each individual and performed low-coverage (1-2x) whole genome sequencing. The cfDNA fragmentome data were analyzed with our DELFI (DNA evaluation of fragments for early interception) approach optimized for high specificity. We used a cross-validated machine learning model, and the fixed DELFI model was evaluated in the external validation cohort. Results: Individuals with ovarian cancer had significantly higher DELFI scores than those without cancer (mean 0.59 vs 0.18, respectively, p < 0.0001) resulting in an AUC of 0.85 (95% CI = 0.80-0.90). DELFI was successful in identifying high-grade serous ovarian cancer across all stages, with sensitivities of 56%, 60%, 58% and 100% for stages I - IV, respectively, at 99% specificity. We further applied DELFI to evaluate women with ovarian masses in a prospective observational cohort (NL58253.031.16). Women with benign masses had DELFI scores lower than those with ovarian cancer (mean 0.23 vs 0.59, p< .0001) and were distinguished with an overall AUC of 0.80 (95% CI = 0.73-0.86). In the external validation cohort, women with cancer were distinguished from women without cancer with an AUC of 0.88 (95% CI = 0.72 - 1.0). At the DELFI score threshold with 99% specificity in the cross-validated cohort, the external validation cohort had specificity of 97% with an overall sensitivity of 79%. The cfDNA fragmentome profiles reflected chromosomal, chromatin, transcription factor binding site, and disease-specific pathway changes known to be altered in ovarian cancer. We are extending these efforts to over 1000 individuals with and without ovarian cancer and the integrated results will be presented. Conclusion: Overall, we demonstrate the utility of cfDNA fragmentomes for noninvasive detection of ovarian cancer. These results may provide a feasible approach for ovarian cancer screening and management of patients with ovarian masses. Citation Format: Akshaya V. Annapragada, Jamie E. Medina, Pien Lof, Dimitrios Mathios, Zachariah H. Foda, Michaël Noë, Sarah Short, Adrianna Bartolomucci, Daniel C. Bruhm, Euihye Jung, Jenna Canzoniero, Noushin Niknafs, Stephen Cristiano, Vilmos Adleff, Heather Symecko, Daan van de Broek, Stephen B. Baylin, Michael F. Press, Dennis Slamon, Gottfried Konecny, Susan Domchek, Ronny Drapkin, Jillian Phallen, Robert B. Scharpf, Christianne Lok, Victor E. Velculescu. Early detection of ovarian cancer using cell-free DNA fragmentomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 773.

This chapter discusses the need of geospatial data and the new technical tools for data acquisition and maintenance of (topographic) data to support SDGs. The chapter provides an example of data acquisition for urban and high mountain areas.

In December 2011, UNGGIM initiated a cooperative project with ISPRS to resume the former UN Secretariat studies on the status of topographic mapping in the world, conducted between 1968 and 1986. After the design of a questionnaire with 27 questions, the UNGGIM Secretariat sent the questionnaires to the UN member states. 115 replies were received from the 193 member states and regions thereof. Regarding the global data coverage and age, the UN questionnaire survey was supplemented by data from the Eastview database. For each of the 27 questions, an interactive viewer was programmed permitting the analysis of the results. The authoritative data coverage at the various scale ranges has greatly increased between 1986 and 2012. Now, a 30 % 1 : 25 000 map data coverage and a 75 % 1 : 50 000 map data coverage has been completed. Nevertheless, there is still an updating problem, as data for some countries is 10 to 30 years old. Private Industry, with Google, Microsoft and Navigation system providers, have undertaken huge efforts to supplement authoritative mapping. For critical areas on the globe, MGCP committed to military mapping at 1 : 50 000. ISPRS has decided to make such surveys a sustainable issue by establishing a working group.

The status of world topographic mapping and the acquisition of satellite image data for land resource mapping applications are reviewed. Special focus has been placed on results from the German MOMS-02 system, which offers high-resolution, stereoscopic image data for the production of medium-scale maps. It is concluded that topographic mapping from space is on the verge of becoming an operational reality.

The International Federation of Surveyors (FIG) has recently stated that about 30 to 50 countries in the world have cadastral systems in operation. Another 50 countries are in the process of establishing one. The remainder of 90 countries do not have a land registry system and they do not have the funds to establish one.

After disappointing results achieved with older chemosensitivity tests such as the human tumor clonogenic assay (HTCA) during the 1980s, the last decade has seen a renaissance of the concept of individualized chemotherapy in oncology, markedly stimulated by the development of newer nonclonogenic assays. These methods appear to be able to overcome major technical limitations associated with older assays, now allowing for successful testing of most of the tumor specimens submitted. Currently, the ATP-based tumor chemosensitivity assay (ATP-TCA) can be regarded as the most sophisticated assay to investigate both solid samples and effusions derived from patients with various organ tumors. During the last 5 years, the ATP-TCA has been used successfully to screen for novel drug combinations for further clinical use in both ovarian and breast cancer such as mitoxantrone plus paclitaxel (NT) and treosulfan plus gemcitabine (TG), respectively. Clinical trials that have been set up in heavily pretreated patients with recurrent ovarian or breast cancer have convincingly confirmed the high activity of these combinations previously demonstrated in preclinical investigations using the ATP-TCA. In a recent phase II trial performed in 59 patients with relapsed ovarian carcinoma, ATP-TCA-directed therapy was able to triple the response rate and to double the survival time, compared with published empirical chemotherapy regimes. Preliminary results with ATP-TCA-directed therapy in breast cancer also evidenced promising response rates. These results have been confirmed by additional prospective clinical trials using other types of modern nonclonogenic assays. A phase III trial that is now actively recruiting patients with platinum-refractory ovarian cancer to verify the promising phase II studies will prove the further value of the ATP-TCA as a predictor applicable in routine clinical oncology.

The motivation for mapping from space is given by the fact that past conventional mapping methods have not been able to provide adequate mapping coverages at the required scales, except for priority areas.

A survey control system for the Province of New Brunswick is established by tellurometer and geodimeter traverses. The cost per station for monumentation, survey, and electronic computation of coordinates was $78.70. Approximately 500 stations are established per year during the field season of 4 months. The relative accuracy for tellurometer traverses with stations 5 miles to 10 miles apart is 1:65000. The precision for geodimeter traverses with stations 0.5 mile to 2 miles apart is 1:38000. Coordinate control surveys by electronic instruments are therefore more economical and more accurate than previous methods.

A review of the fundamental classical concepts of least squares adjustment, based on the development by Gauss is presented. The method of least squares leads to a most probable value of the adjusted quantity under the assumption that the arithmetic mean yields the most probable result and that the uncorrelated observations are normally distributed. It is shown further that the method of least squares leads to an adjusted value with a resulting smallest standard error for any symmetrical distribution. It is indicated that this is also true for correlated observations and that various statistical tests make least squares adjustment a powerful tool for statistical analysis.

An adequate environmental data bank must be based on geometrically defined parcels of land. A distinction is made between the description of an area of land and its definition. To define land parcels properly, a network of permanent control points is required. Where such a network is lacking, large-scale maps can serve as substitutes, but the precision of definition will be inferior. The paper gives suggestions for indexing land parcels, the types of files in a data bank and the establishment of a national bank of control survey data. The author’s final conclusion is that there is no better assurance for the long-term value of a data bank than the use of control surveys for its geometrical foundation.

The writers make a theoretical accuracy comparison between triangulation, trilateration, combined triangulation and trilateration and traversing for secondary control survey nets, connecting previously established primary control.

The paper emphasizes that the choice of a proper procedure is essential for efficient glacier surveying. Terrestrial versus aerial photogrammetry and the use of electronic surveying procedures versus triangulation have been tested in surveys on the Athabasca and Saskatchewan glaciers, and on glaciers in northern Ellesmere Island, southeastern Alaska, and the Yukon Territory. The Otto Fiord glacier survey in northern Ellesmere Island demonstrates that no ground control is needed for volumetric glacier studies. Accurate maps needed for other studies depend on the establishment of control. Control can most efficiently be determined by tellurometer and phototheodolite with helicopter support, as shown in Alaskan glacier surveys. For large glaciers phototopography provides a good means of extending control from tellurometer traverse stations, as demonstrated in the Mount Kennedy survey. Simple one-color maps are an economical means of preserving survey results for future glaciological evaluation.

A large portion of infrared radiation can only be recorded photographically with special sensing devices. Such images show much similarity to photographs taken by a continuous strip camera, but have a somewhat different geometry and distortion characteristic. The principal sources of distortions are scanning technique distortion, errors of exterior orientation elements, velocity errors of the aircraft, errors of interior orientation elements, distortions of the optical and electronic system and errors of the recording device. The magnitude of these errors is demonstrated by numerical examples.

This paper and the following paper by T. J. Blachut were delivered originally at the North American Symposium on Urban Surveying and Mapping, Mexico City, in January 1969. They are presented here, ...

Photogrammetry (photography from aircraft) is now considered the standard topographic data acquisition tool the world over and yet, progress in mapping from aerial photographs is so slow that it has accomplished no more than 40–45% of the desired topographic map coverage at the necessary scales of 1:50 000 or 1:100 000. With existing methods of aerial photogrammetry, it will not be possible to achieve world land coverage at these scales by the year 2000.

(1985). Greetings from International Society for Photogrammetry and Remote Sensing (ISPRS) Cartography: Vol. 14, No. 1, pp. 24-24.