Role of brachytherapy in the treatment of cancers of the anal canal. Long-term follow-up and multivariate analysis of a large monocentric retrospective series.

BACKGROUND AND PURPOSE: There are few data on long-term clinical results and tolerance of brachytherapy in anal canal cancer. We present one of the largest retrospective analyses of anal canal cancers treated with external beam radiotherapy with/without (±) chemotherapy followed by a brachytherapy boost. MATERIALS AND METHODS: We performed a retrospective analysis of clinical results in terms of efficacy and toxicity. The impact of different clinical and therapeutic variables on these outcomes was studied. RESULTS: From May 1992 to December 2009, 209 patients received brachytherapy after external beam radiotherapy ± chemotherapy. Of these patients, 163 were stage II or stage IIIA (UICC 2002) and 58 were N1-3. According to age, ECOG performance status (PS), and comorbidities, patients received either radiotherapy alone (58/209) or radiochemotherapy (151/209). The median follow-up was 72.8 months. The 5- and 10-year local control rates were 78.6 and 73.9 %, respectively. Globally, severe acute and late G3-4 reactions (NCI-CTC scale v. 4.0) occurred in 11.2 and 6.3 % of patients, respectively. Univariate analysis showed the statistical impact of the pelvic treatment volume (p = 0.046) and of the total dose (p = 0.02) on the risk of severe acute and late toxicities, respectively. Only six patients required permanent colostomy because of severe late anorectal toxicities. CONCLUSION: After a long follow-up time, brachytherapy showed an acceptable toxicity profile and high local control rates in patients with anal canal cancer

Deep-ocean mixing driven by small-scale internal tides

Turbulent mixing in the ocean is key to regulate the transport of heat, freshwater and biogeochemical tracers, with strong implications for Earth’s climate. In the deep ocean, tides supply much of the mechanical energy required to sustain mixing via the generation of internal waves, known as internal tides, whose fate—the relative importance of their local versus remote breaking into turbulence—remains uncertain. Here, we combine a semi-analytical model of internal tide generation with satellite and in situ measurements to show that from an energetic viewpoint, small-scale internal tides, hitherto overlooked, account for the bulk (>50%) of global internal tide generation, breaking and mixing. Furthermore, we unveil the pronounced geographical variations of their energy proportion, ignored by current parameterisations of mixing in climate-scale models. Based on these results, we propose a physically consistent, observationally supported approach to accurately represent the dissipation of small-scale internal tides and their induced mixing in climate-scale models

Uncertainty information in climate data records from Earth observation

Climate data records (CDRs) derived from Earth observation (EO) should include rigorous uncertainty information, to support application of the data in policy, climate modelling and numerical weather prediction reanalysis. Uncertainty, error and quality are distinct concepts, and CDR products should follow international norms for presenting quantified uncertainty. Ideally, uncertainty should be quantified per datum in a CDR, and the uncertainty estimates should be able to discriminate more and less certain data with confidence. In this case, flags for data quality should not duplicate uncertainty information, but instead describe complementary information (such as the confidence held in the uncertainty estimate provided, or indicators of conditions violating retrieval assumptions). Errors have many sources and some are correlated across a wide range of time and space scales. Error effects that contribute negligibly to the total uncertainty in a single satellite measurement can be the dominant sources of uncertainty in a CDR on large space and long time scales that are highly relevant for some climate applications. For this reason, identifying and characterizing the relevant sources of uncertainty for CDRs is particularly challenging. Characterisation of uncertainty caused by a given error effect involves assessing the magnitude of the effect, the shape of the error distribution, and the propagation of the uncertainty to the geophysical variable in the CDR accounting for its error correlation properties. Uncertainty estimates can and should be validated as part of CDR validation, where possible. These principles are quite general, but the form of uncertainty information appropriate to different essential climate variables (ECVs) is highly variable, as confirmed by a quick review of the different approaches to uncertainty taken across different ECVs in the European Space Agency’s Climate Change Initiative. User requirements for uncertainty information can conflict with each other, and again a variety of solutions and compromises are possible. The concept of an ensemble CDR as a simple means of communicating rigorous uncertainty information to users is discussed. Our review concludes by providing eight recommendations for good practice in providing and communicating uncertainty in EO-based climate data records

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkage between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function. However, the mechanism by which abacavir induces this pathologic T cell response remains unclear. Here we show that abacavir can bind within the F-pocket of the peptide-binding groove of HLA-B*57:01 thereby altering its specificity. This supports a novel explanation for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can alter the repertoire of self-peptides presented to T cells thus causing the equivalent of an alloreactive T cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir, and that were recognized by T cells of hypersensitive patients. The assays we have established can be applied to test additional compounds with suspected HLA linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA linked hypersensitivities as well as guide the development of safer drugs

Topographic shelf waves control seasonal melting near Antarctic Ice Shelf grounding lines

The buttressing potential of ice shelves is modulated by changes in subshelf melting, in response to changing ocean conditions. We analyze the temporal variability in subshelf melting using an autonomous phase-sensitive radio-echo sounder near the grounding line of the Roi Baudouin Ice Shelf in East Antarctica. When combined with additional oceanographic evidence of seasonal variations in the stratification and the amplification of diurnal tides around the shelf break topography (Gunnerus Bank), the results suggest an intricate mechanism in which topographic waves control the seasonal melt rate variability near the grounding line. This mechanism has not been considered before and has the potential to enhance local melt rates without advecting different water masses. As topographic waves seem to strengthen in a stratified ocean, the freshening of Antarctic surface water, predicted by observations and models, is likely to increase future basal melting in this area. \ud Plain Language Summary Ice shelves (or the floating parts of the Antarctic ice sheet) lose primarily mass through melting at their bottom in contact with the ocean. This thins them and makes them more vulnerable to potential collapse. To understand the processes governing such thinning, direct and long-time measurements are essential. Here we report on the first high-resolution time series of direct melt measurements on the Roi Baudouin Ice Shelf in Dronning Maud Land during 2016. We find that subshelf melt varies on both seasonal and daily time scales. Temporal variations stem from topographical ocean waves that originate on the continental shelf and transfer ocean properties without time delay within the ice shelf cavity. Therefore, seasonal variations highly depend on the presence/absence of sea ice in front of the ice shelf, which impact the strength of topographical waves. This mechanism is highly efficient at increasing the ice-ocean exchanges and may explain regional differences in ice shelf melt

Climate recorded in seawater: A workshop on water-mass transformation analysis for ocean and climate studies

First workshop on water-mass transformation analysis for ocean physics, biogeochemistry, and climate. 4–6 February 2019, Sydney, New South Wales, AustraliaInternational audienceAn international cohort of oceanographers, marine biogeochemists, and climate modelers gathered to expand the use of water-mass transformation diagnostics in studies of ocean physics, biogeochemistry, and climate. Led by early-career scientists, the group laid out avenues to leverage growing oceanic observational databases and new model capabilities, using fundamental understanding of the ocean’s layering

Decision process in large-scale crisis management

International audienceThis paper deals with the decision-aiding process in large-scale crisis such as natural disasters. It consists in four phases: decision context characterization, system modelling, aggregation and integration. The elements of the context, such as crisis level, risk situation, decision-maker problem issue are defined through the characterization phase. At the feared event occurrence, these elements will interact on a target system. Through the model on this system, the consequences to stakes could be assessed or estimated. The presented aggregation approaches will allow taking the right decisions. The architecture of a Decision Support System is presented in the integration phase

Historical changes in the stomatal limitation of photosynthesis: empirical support for an optimality principle

The ratio of leaf‐internal (ci) to ambient (ca) partial pressure of CO2, defined here as χ, is an index of adjustments in both leaf stomatal conductance and photosynthetic rate to environmental conditions. Measurements and proxies of this ratio can be used to constrain vegetation models uncertainties for predicting terrestrial carbon uptake and water use. We test a theory based on the least‐cost optimality hypothesis for modelling historical changes in χ over the 1951‐2014 period, across different tree species and environmental conditions, as reconstructed from stable carbon isotopic measurements across a global network of 103 absolutely‐dated tree‐ring chronologies. The theory predicts optimal χ as a function of air temperature, vapour pressure deficit, ca and atmospheric pressure. The theoretical model predicts 39% of the variance in χ values across sites and years, but underestimates the inter‐site variability in the reconstructed χ trends, resulting in only 8% of the variance in χ trends across years explained by the model. Overall, our results support theoretical predictions that variations in χ are tightly regulated by the four environmental drivers. They also suggest that explicitly accounting for the effects of plant‐available soil water and other site‐specific characteristics might improve the predictions

A combined microbial and biogeochemical dataset from high-latitude ecosystems with respect to methane cycle.

High latitudes are experiencing intense ecosystem changes with climate warming. The underlying methane (CH4) cycling dynamics remain unresolved, despite its crucial climatic feedback. Atmospheric CH4 emissions are heterogeneous, resulting from local geochemical drivers, global climatic factors, and microbial production/consumption balance. Holistic studies are mandatory to capture CH4 cycling complexity. Here, we report a large set of integrated microbial and biogeochemical data from 387 samples, using a concerted sampling strategy and experimental protocols. The study followed international standards to ensure inter-comparisons of data amongst three high-latitude regions: Alaska, Siberia, and Patagonia. The dataset encompasses diferent representative environmental features (e.g. lake, wetland, tundra, forest soil) of these high-latitude sites and their respective heterogeneity (e.g. characteristic microtopographic patterns). The data included physicochemical parameters, greenhouse gas concentrations and emissions, organic matter characterization, trace elements and nutrients, isotopes, microbial quantifcation and composition. This dataset addresses the need for a robust physicochemical framework to conduct and contextualize future research on the interactions between climate change, biogeochemical cycles and microbial communities at highlatitudes