Contents lists available at ScienceDirect

journal homepage: www.elsevier.com/locate/palae

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Multiproxy environmental characterization of lake level cycles in the Green River Formation of Utah and Colorado

The Eocene Green River Formation represents one of the largest petroleum resources in the world, and certainly the largest petroleum resource in the state of Utah. While the oil shales have figured prominently in the literature for the past century, surprisingly little basic knowledge of the geochemistry of these deposits exists, especially within the contex t of the characteristic and permeating lacustrine cyclicity. Competing theories of tectonic versus climatic drivers for these cycles make different predictions about the nature of the oil-shale geochemistry and are thus important in understanding the predictability of oil-shale resources, especially in other lacustrine petroleum systems that are geologically less well characterized. Here we document the ecosystem context of the lacustrine cyclicity using sedimentary facies, oil-shale yield, bulk nitrogen (?15N) and carbon isotopic (?13C) signatures of organic matter, and specific biomarker hydrocarbons (?13C alk) sampled at millennial resolution through a series of cycles at multiple localities in core and outcrop. This project is relevant to solicitation purposes (#2) oil resource potential and (#3) unconventional oil and gas resources such as tar sands and oil shale; it should lead to a greater understanding of the most fundamental aspects of the depositional history of these oil shales as well as the predictive power of facies models, all of which should ultimately play a part in Utah’s hydrocarbon potential and U.S. petroleum independence

Synchrony between the Central Atlantic

www.elsevier.com/locate/palae

Spatial and Temporal Patterns in Petrogenic Organic Carbon Mobilisation during the Paleocene-Eocene Thermal Maximum

The Paleocene-Eocene Thermal Maximum (PETM) was a transient global warming event recognised in the geologic record by a prolonged negative carbon isotope excursion (CIE). The onset of the CIE was the result of a rapid influx of 13C-depleted carbon into the ocean-atmosphere system. However, the mechanisms required to sustain the negative CIE remains unclear. Previous studies have identified enhanced mobilisation of petrogenic organic carbon (OCpetro) and argued that this was likely oxidised, increasing atmospheric carbon dioxide (CO2) concentrations after the onset of the CIE. With existing evidence limited to the mid-latitudes and subtropics, we determine whether: (i) enhanced mobilisation and subsequent burial of OCpetro in marine sediments was a global phenomenon; and (ii) whether it occurred throughout the PETM. To achieve this, we utilised a lipid biomarker approach to trace and quantify OCpetro burial in a global compilation of PETM-aged shallow marine sites (n = 7, including five new sites). Our results confirm that OCpetro mass accumulation rates (MARs) increased within the subtropics and mid-latitudes during the PETM, consistent with evidence of higher physical erosion rates and intense episodic rainfall events. The high-latitude sites do not exhibit distinct changes in the organic carbon source during the PETM. This may be due to the more stable hydrological regime and/or additional controls. Crucially, we also demonstrate that OCpetro MARs remained elevated during the recovery phase of the PETM. Although OCpetro oxidation was likely an important positive feedback mechanism throughout the PETM, we show that this feedback was both spatially and temporally variable

Paleogene Newfoundland sediment drifts

Integrated Ocean Drilling Program Expedition 342 was designed to recover Paleogene sedimentary sequences with unusually high deposition rates across a wide range of water depths (Sites U1403–U1411). The drilling area is positioned to capture sedimentary and geochemical records of ocean chemistry and overturning circulation beneath the flow of the Deep Western Boundary Current in the northwest Atlantic Ocean. In addition, two operational days were dedicated to a sea trial of the Motion Decoupled Hydraulic Delivery System developmental tool (Site U1402). The expedition was primarily targeted at reconstructing the Paleogene carbonate compensation depth (CCD) in the North Atlantic for reference to recently obtained high-fidelity records of the CCD in the equatorial Pacific. The site located in the deepest water (Site U1403) was at a paleodepth of ~4.5 km 50 m.y. ago, whereas the site located in the shallowest water (Site U1408) can be backtracked to a paleodepth of 2.5 km at the same time. The combination of sites yields a record of the history of CCD change over a 2 km depth range from the ocean abyss to middle range water depths. Notable findings include the discovery of intermittent calcareous sediments in the Cretaceous, Paleocene, and early to middle Eocene at 4.5 km paleodepth, suggesting a deep Atlantic CCD during these times. We find evidence of carbonate deposition events following the Cretaceous/Paleogene (K/Pg) boundary mass extinction, the Paleocene/Eocene Thermal Maximum, and the Eocene–Oligocene transition. These deposition events may reflect the rebalancing of ocean alkalinity after mass extinctions or abrupt global climate change. Intervals during which the CCD appears to have been markedly shallow in the North Atlantic include the Early Eocene Climatic Optimum, the late Eocene, and the middle Oligocene. A second major objective of Expedition 342 was to recover clay-rich sequences with well-preserved microfossils and high rates of accumulation in comparison to the modest rates of accumulation (~0.5–1 cm/k.y. in the Paleogene) typically encountered at pelagic sites. As anticipated, Expedition 342 recovered sequences with sedimentation rates of as much as 10 cm/k.y.—high enough to enable studies of the dynamics of past abrupt climate change, including both transitions into “greenhouse” and “icehouse” climate states, the full magnitudes of hyperthermal events, and rates of change in the CCD. We find that the thickest central parts of the various sediment drifts typically record similar depositional packages to those recovered in the thin “noses” and “tails” of these drifts, but these central parts are often massively expanded with clay, especially near the CCD. Times of rapid accumulation of drift deposits include the early Eocene to late middle Eocene, the late Eocene to early Oligocene, the late Oligocene and early Miocene, the later Miocene to probable late Pliocene, and the Pleistocene. Widespread hiatuses are present near the Paleocene/Eocene boundary into the middle early Eocene and the middle Oligocene. The Eocene/Oligocene boundary is a period of slow sedimentation at most sites but is expanded at Site U1411. A marked change in the geometry of drift formation is observed in the ?late Pliocene, as has been observed in drift deposits elsewhere. An unexpected finding was the recovery of a number of Cretaceous “critical boundaries.” These include the K/Pg boundary, the Campanian–Coniacian interval, the Cenomanian–Turonian boundary and oceanic anoxic event (OAE) 2, and the Albian/Cenomanian boundary OAE 1d. These intervals were drilled opportunistically when they were encountered near or above our target depth for a given site. The K/Pg boundary was recovered at Site U1403, where it proved to have a well-preserved, normally graded spherule bed and unusually well preserved earliest Danian planktonic foraminifer community. The Campanian–Coniacian interval was cored at Site U1407 and is unusual mainly for the relative biostratigraphic completeness of a sequence that elsewhere commonly shows hiatuses in the early Campanian. The Cenomanian–Turonian transition was also cored at Site U1407 and consists of a series of organic black shales in nannofossil chalk with as much as 11 wt% total organic carbon (TOC). The Cenomanian–Turonian sequence at Site U1407 is broadly similar in biostratigraphy, sequence of black shales, and sediment color to classic Italian and northern German outcrop sections. Finally, coring at Site U1407 also recovered a lower Cenomanian nannofossil chalk and nannofossil claystone record that extends into the biozones associated with OAE 1d. The Albian–Cenomanian sequence is notable for the generally high quality of microfossil preservation and its gradational contact with underlying Albian shallow-marine carbonate grainstone and packstone. We created high-quality spliced records of most of the sites on Southeast Newfoundland Ridge that penetrate sequences with carbonate-rich lithologies. As anticipated, the task of creating spliced records in the more clay-rich lithologies in some sites was not straightforward due to intervals of low-amplitude change in some physical properties data sets. All sites also proved to have differences in stratigraphy between adjacent holes showing that there is often considerable local variation within the drift sequences. Particularly expanded sedimentary sequences were drilled in Miocene–Oligocene, Eocene–Oligocene, and middle Eocene sequences. Comparison of our drilling results with seismic stratigraphy from the Southeast Newfoundland Ridge indicates large-scale lateral changes in age and thickness of sediment drift packages, regionally meaning that the area presents an attractive target for future expeditions aimed at recovering high deposition–rate records from many parts of the Cenozoic