Target Therapy in Platinum-Refractory/Resistant Ovarian Cancer: From Preclinical Findings to Current Clinical Practice

Epithelial ovarian cancer (EOC) is the sixth most common malignancy in women. Ovarian tumors consist of several clinical and pathological entities that share an anatomic site. The gold standard treatment, both in front-line and in adjuvant setting, is represented by carboplatin/paclitaxel combination. Conversely, the second-line treatment is not well defined. The response to platinum is the major prognostic factor for survival. In this review we discuss the current views on platinum-refractory/resistant patient treatment only, which includes patients progressing or relapsing within 6 months from the last platinum-based course. Concerning this subgroup, the activity of several conventional drugs was confirmed in different trials without a significant impact in terms of overall survival. In the last years particular emphasis was given to targeted anti-angiogenetic therapy which produced a survival improvement with an acceptable toxicity profile. New “ad hoc” approaches, with a major attention to outcome-predictive factors, are eagerly awaited

Phthalates and Bisphenol A: presence in blood serum and follicular fluid of italian women undergoing assisted reproduction techniques

Background: folliculogenesis is a strictly regulated process that may be affected by endocrine disrupting chemicals (EDCs) through sometimes not so clear molecular mechanisms. Methods: we conducted a multicentric observational study involving six fertility centers across Italy, prospectively recruiting 122 women attending a fertility treatment. Recruited women had age ≤42 years, and normal ovarian reserve. Blood and follicular fluid samples were taken for EDCs measurement using liquid chromatography tandem mass spectrometry and each woman completed an epidemiological questionnaire. Results: The main EDCs found were monobutyl phthalate (MBP) (median blood: 8.96 ng/mL, follicular fluid 6.43 ng/mL), monoethylhexyl phthalate (MEHP) (median blood: 9.16 ng/mL, follicular fluid 7.68 ng/mL) and bisphenol A (BPA) (median blood: 1.89 ng/mL, follicular fluid 1.86 ng/mL). We found that serum MBP concentration was significantly associated with the considered area (p < 0.001, adj. mean: 7.61 ng/mL, 14.40 ng/mL, 13.56 ng/mL; Area 1: Milan–Turin, Area 2: Rome–Naples; Area 3: Catania–Bari, respectively) but negatively with home plastic food packaging (p = 0.004). Follicular MBP was associated with irregular cycles (p = 0.019). No association was detected between EDCs and eating habits and other clinical and epidemiological features. Conclusions: This study represents the first Italian biomonitoring of plastic EDCs in follicular fluid, laying the basis for future prospective evaluation on oocyte quality before assisted reproduction techniques (ART

It's getting hot in here – Microcontextual study of a potential pit hearth at the Middle Paleolithic site of El Salt, Spain

By studying combustion structures, which conceal information about anthropogenic activity, we might learn about their makers. This is especially important for remote time periods like the Middle Paleolithic, whose archaeological record comprises numerous combustion structures. The majority of these are simple, flat, open hearths, although a small number of features situated in pit-like depressions have been recorded. Given that hearths built on a flat surface can result in pit-like color alteration of the underlying sediment, accurate identification of pit hearths is a crucial step prior to behavioral interpretation. Here we present a comprehensive study of a possible pit hearth from the Middle Paleolithic site of El Salt, Spain, using a microcontextual approach combining micromorphology, lipid biomarker analysis, archaeomagnetism and zooarchaeology. This pit hearth involves a true depression containing a thick plant ash deposit. It reached very high temperatures, possibly multiple burning events and long combustion times. Morphologically distinct combustion structures in a single archaeological context may indicate different functions and thus a diverse fire technology, pointing to Neanderthal behavioral variability.ERC Consolidator Grant project PALEOCHAR – 648871 https://erc.europa.eu/funding/consolidator-grants, I + D Project HAR2008-06117/HIST, HAR2015-68321-P (MINECO-FEDER/UE), and the Cultural Heritage Department of the Valencia Government and the Archaeological Museum Camil Visedo of Alcoy, under the direction of Professor Bertila Galván of Universidad de La Laguna, Junta de Castilla y León (project BU235P18), the European Fund for Economic and Regional Development (EFRD) and the project PID2019-105796 GB-I00 of the Agencia Estatal de Investigación (AEI/10.13039/501100011033

Multi-phase seismic source imprint of tropical cyclones

International audienceThe coupling between the ocean activity driven by winds and the solid Earth generates seismic signals recorded by seismometers worldwide. The 2-10 s period band, known as secondary microseism, represents the largest background seismic wavefield. While moving over the ocean, tropical cyclones generate particularly strong and localized sources of secondary microseisms that are detected remotely by seismic arrays. We assess and compare the seismic sources of P, SV, and SH waves associated with typhoon Ioke (2006) during its extra-tropical transition. To understand their generation mechanisms, we compare the observed multi-phase sources with theoretical sources computed with a numerical ocean wave model, and we assess the influence of the ocean resonance (or ocean site effect) and coastal reflection of ocean waves. We show how the location and lateral extent of the associated seismic source is period-and phase-dependent. This information is crucial for the use of body waves for ambient noise imaging and gives insights about the sea state, complementary to satellite data

Rayleigh-wave attenuation across the conterminous United States in the microseism frequency band

International audienceMapping variations in the attenuation of seismic energy is important for understanding dissipative mechanisms in the lithosphere, and for modeling ground shaking associated with earthquakes. We cross-correlate ambient seismic signal recorded across the EarthScope Transportable Array in the 3–15 s period range. We apply to the resulting cross correlations a new method to estimate lateral variations in Rayleigh-wave attenuation, as a function of period, beneath North America. Between 3 and 6 s, our maps are dominated by a strong eastward decrease in attenuation. This pattern vanishes at longer periods, confirming early observations based on regional earthquakes. Attenuation maps and phase-velocity maps are anti-correlated at periods between 3 and 6 s, but the anti-correlation is also largely lost at longer periods. This corresponds to the attenuation coefficient decreasing with period more rapidly in the west than in the east, while the change in phase velocity with period is more uniform across the continent. Our results point to a transition in the properties of upper-crustal materials with depth, probably related to the closure of fluid-filled cracks and pores, and imply that measures of attenuation from seismic noise carry significant information on crustal rheology

On the shaping factors of the secondary microseismic wavefield

International audienceSeismic noise in the period band 3–10 s is known as secondary microseism, and it is generated at the ocean surface by the interaction of ocean gravity waves coming from nearly opposite directions. In this paper, we investigate the seismic content of the wavefield generated by a source at the ocean surface and three of the major wavefield shaping factors using the 2-D spectral element method: the ocean-continent boundary, the source site effect, and the thickness of seafloor sediments. The seismic wavefield recorded on the vertical component seismograms below the seafloor is mainly composed of the fundamental mode and the first overtone of Rayleigh waves. A mode conversion from the first overtone to the fundamental mode of Rayleigh waves occurs at the ocean-continent boundary. The presence of a continental shelf at the ocean-continent boundary produces a negligible effect on land-recorded seismograms, whereas the source site effect, i.e., the source location with respect to the local ocean depth and sediment thickness, plays the major role. A source in shallow water mostly enhances the fundamental mode of Rayleigh waves, whereas a source in deep water mainly enhances the first overtone of Rayleigh waves. Land-recorded long-period signals (T > 6 s) are mostly due to deep water sources, whereas land-recorded short-period signals (T 6 s)

Modelling the ocean site effect on seismic noise body waves

Secondary microseismic noise is generated by non-linear interactions between ocean waves at the ocean surface. We present here the theory for computing the site effect of the ocean layer upon body waves generated by noise sources distributed along the ocean surface. By defining the wavefield as the superposition of plane waves, we show that the ocean site effect can be described as the constructive interference of multiply reflected P waves in the ocean that are then converted to either P or SV waves at the ocean-crust interface. We observe that the site effect varies strongly with period and ocean depth, although in a different way for body waves than for Rayleigh waves. We also show that the ocean site effect is stronger for P waves than for S waves. We validate our computation by comparing the theoretical noise body wave sources with the sources inferred from beamforming analysis of the three seismogram components recorded by the Southern California Seismic Network. We use rotated traces for the beamforming analysis, and we show that we clearly detect P waves generated by ocean gravity wave interactions along the track of typhoon Ioke (2006 September). We do not detect the corresponding SV waves, and we demonstrate that this is because their amplitude is too weak

The persistent signature of tropical cyclones in ambient seismic noise

The spectrum of ambient seismic noise shows strong signals associated with tropical cyclones, yet a detailed understanding of these signals and the relationship between them and the storms is currently lacking. Through the analysis of more than a decade of seismic data recorded at several stations located in and adjacent to the northwest Pacific Ocean, here we show that there is a persistent and frequency-dependent signature of tropical cyclones in ambient seismic noise that depends on characteristics of the storm and on the detailed location of the station relative to the storm. An adaptive statistical model shows that the spectral amplitude of ambient seismic noise, and notably of the short-period secondary microseisms, has a strong relationship with tropical cyclone intensity and can be employed to extract information on the tropical cyclones