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

Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning

The RAMI On-line Model Checker (ROMC): A web-based benchmarking facility for canopy reflectance models

The exploitation of global Earth Observation data hinges increasingly on physically-based radiative transfer (RT) models. These models simulate the interactions of solar radiation within a given medium (e.g., clouds, plant canopies) and are used to generate look-up-tables that are embedded into quantitative retrieval algorithms, such as those delivering the operational surface products for MODIS, MISR and MERIS. An assessment of the quality of canopy RT models thus appears essential if accurate and reliable information is to be derived from them. Until recently such an undertaking was a time consuming and labour intensive process that was made even more challenging by the general lack of absolute reference standards. Several years of benchmarking activities in the frame of the RAdiation transfer Model Intercomparison (RAMI) exercise have now led to the development of the RAMI On-line Model Checker (ROMC). The ROMC is a web-based tool allowing model developers and users to autonomously assess the performance of canopy RT models (http://romc.jrc.ec.europa.eu/). Access to the ROMC is free and enables users to obtain both statistical and graphical indications as to the performance of their canopy RT model. In addition to providing an overall indication of the skill of a given model to correctly match the reference data, the ROMC allows also for interactive comparison/evaluations of different model versions/submissions of a given user. AllROMCgraphs can be downloaded in PostScript format and come with a reference number for easy usage in presentations and publications. It is hoped that the ROMC will prove useful for the RT modeling community as a whole, not only by providing a convenient means to evaluate models outside the triennial phases of RAMI but also to attract participation in future RAMI activities

Charge and current-sensitive preamplifiers for pulse shape discrimination techniques with silicon detectors

New charge and current-sensitive preamplifiers coupled to silicon detectors and devoted to studies in nuclear structure and dynamics have been developed and tested. For the first time shapes of current pulses from light charged particles and carbon ions are presented. Capabilities for pulse shape discrimination techniques are demonstrated.Comment: 14 pages, 12 figures, to be published in Nucl. Inst. Meth.

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

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

Fragmentation branching ratios of highly excited hydrocarbon molecules CnH and their cations CnH+ (n<4)

We have measured fragmentation branching ratios of neutral CnH and CnH+ cations produced in high velocity (4.5 a.u) collisions between incident CnH+ cations and helium atoms. Electron capture gives rise to excited neutral species CnH and electronic excitation to excited cations CnH+. Thanks to a dedicated set-up, based on coincident detection of all fragments, the dissociation of the neutral and cationic parents were recorded separately and in a complete way. For the fragmentation of CnH, the H-loss channel is found to be dominant, as already observed by other authors. By contrast, the H-loss and C-loss channels equally dominate the two-fragment break up of CnH+ species. For these cations, we provide the first fragmentation data (n > 2). Results are also discussed in the context of astrochemistry

Barents-2.5km v2.0: An operational data-assimilative coupled ocean and sea ice ensemble prediction model for the Barents Sea and Svalbard

An operational ocean and sea ice forecast model, Barents-2.5, is implemented at MET Norway for short-term forecasting at the coast off Northern Norway, the Barents Sea, and waters around Svalbard. Primary forecast parameters are the sea ice concentration (SIC), sea surface temperature (SST), and ocean currents. The model is also a substantial input for drift modeling of pollutants, ice berg, and in search-and-rescue pertinent applications in the Arctic domain. Barents-2.5 has recently been upgraded to include an Ensemble Prediction System with 24 daily realizations of the model state. SIC, SST and in-situ hydrography are constrained through the Ensemble Kalman Filter (EnKF) data assimilation scheme executed in daily forecast cycles with lead time up to 66 hours. While the ocean circulation is not directly constrained by assimilation of ocean currents, the model ensemble represents the given uncertainty in the short-term current field by retaining the current state for each member throughout forecast cycles. Here we present the model setup and a validation in terms of SIC, SST and in-situ hydrography. The performance of the ensemble to represent the models uncertainty, and the performance of the EnKF to constrain the model state are discussed, in addition to the model&rsquo;s forecast capabilities for SIC and SST.</p