A Preliminary Study of Magnetosphere-Ionosphere-Thermosphere Coupling at Jupiter: Juno Multi-Instrument Measurements and Modeling Tools.

The dynamics of the Jovian magnetosphere are controlled by the interplay of the planet's fast rotation, its main iogenic plasma source and its interaction with the solar wind. Magnetosphere-Ionosphere-Thermosphere (MIT) coupling processes controlling this interplay are significantly different from their Earth and Saturn counterparts. At the ionospheric level, they can be characterized by a set of key parameters: ionospheric conductances, electric currents and fields, exchanges of particles along field lines, Joule heating and particle energy deposition. From these parameters, one can determine (a) how magnetospheric currents close into the ionosphere, and (b) the net deposition/extraction of energy into/out of the upper atmosphere associated to MIT coupling. We present a new method combining Juno multi-instrument data (MAG, JADE, JEDI, UVS, JIRAM and Waves) and modeling tools to estimate these key parameters along Juno's trajectories. We first apply this method to two southern hemisphere main auroral oval crossings to illustrate how the coupling parameters are derived. We then present a preliminary statistical analysis of the morphology and amplitudes of these key parameters for eight among the first nine southern perijoves. We aim to extend our method to more Juno orbits to progressively build a comprehensive view of Jovian MIT coupling at the level of the main auroral oval.

Cryptic diversity in Amazonian frogs: Integrative taxonomy of the genus Anomaloglossus (Amphibia: Anura: Aromobatidae) reveals a unique case of diversification within the Guiana Shield.

Lack of resolution on species boundaries and distribution can hamper inferences in many fields of biology, notably biogeography and conservation biology. This is particularly true in megadiverse and under-surveyed regions such as Amazonia, where species richness remains vastly underestimated. Integrative approaches using a combination of phenotypic and molecular evidence have proved extremely successful in reducing knowledge gaps in species boundaries, especially in animal groups displaying high levels of cryptic diversity like amphibians. Here we combine molecular data (mitochondrial 16S rRNA and nuclear TYR, POMC, and RAG1) from 522 specimens of Anomaloglossus, a frog genus endemic to the Guiana Shield, including 16 of the 26 nominal species, with morphometrics, bioacoustics, tadpole development mode, and habitat use to evaluate species delineation in two lowlands species groups. Molecular data reveal the existence of 18 major mtDNA lineages among which only six correspond to described species. Combined with other lines of evidence, we confirm the existence of at least 12 Anomaloglossus species in the Guiana Shield lowlands. Anomaloglossus appears to be the only amphibian genus to have largely diversified within the eastern part of the Guiana Shield. Our results also reveal strikingly different phenotypic evolution among lineages. Within the A. degranvillei group, one subclade displays acoustic and morphological conservatism, while the second subclade displays less molecular divergence but clear phenotypic divergence. In the A. stepheni species group, a complex evolutionary diversification in tadpole development is observed, notably with two closely related lineages each displaying exotrophic and endotrophic tadpoles.

Cryptic diversity in the Hypsiboas semilineatus species group (Amphibia, Anura) with the description of a new species from the eastern Guiana Shield.

We used molecular and morphological data to investigate the hidden diversity within the Hypsiboas semilineatus species group, and more specifically within H. geographicus, an allegedly widespread species in northern South America. As a result, the identity of H. geographicus was clarified, several candidate species were detected and one of them, from the eastern Guiana Shield, is described herein as a preliminary step to resolve the taxonomy of the group. Hypsiboas diabolicus sp. nov. is mainly distinguished from closely-related species by an acuminate snout in lateral view, well-developed webbing between fingers and toes, and unspotted carmine/crimson colouration on the concealed surfaces of legs, feet and hands in life. The tadpole of the new species is described and is characterized by a large A-2 gap, a mostly single row of large marginal papillae, and a dark brown to black colouration. We also describe the advertisement call of the new species, which is defined as a soft call consisting of short clusters of 2-3 chuckles with a dominant frequency ranging between 1.11-1.19 kHz. Hypsiboas diabolicus sp. nov. is currently known only from the eastern Guiana Shield, and is probably endemic to that region. The new species' range overlaps broadly with another candidate species referred to as H. aff. semilineatus 1. Our preliminary results stress out a high cryptic diversity in that species group and the need for a formal redescription of Hypsiboas geographicus based on more topotypic material than what is currently available  to properly sort out the taxonomic status of several lineages in that clade.

A new Dendropsophus Fitzinger, 1843 (Anura: Hylidae) of the parviceps group from the lowlands of the Guiana Shield.

Many Amazonian frog species that are considered widely distributed may actually represent polyspecific complexes.. A minute tree frog from the Guiana Shield originally assigned to the allegedly widely distributed Dendropsophus brevifrons proved to be a yet undescribed species within the D. parviceps group. We herein describe this new species and present a phylogeny for the D. parviceps group. The new species is diagnosed from other Dendropsophus of the parviceps group by its small body size (19.6-21.7 mm in males, 22.1-24.5 mm in females), thighs dorsally dark grey with cream blotches without bright yellow patch, absence of dorsolateral and canthal stripe, and an advertisement call comprising trills (length 0.30-0.35 s) composed of notes emitted at a rate of 131-144 notes/s, generally followed by click series of 2-3 notes. Its tadpole is also singular by having fused lateral marginal papillae and absence of both labial teeth and submarginal papillae. Genetic distances (p-distance) are >5.3% on the 12S and >9.3% on the 16S from D. brevifrons, its closest relative. This species occurs from the Brazilian state of Amapá, across French Guiana and Suriname to central Guyana and is likely to also occur in adjacent Brazilian states and eastern Venezuela. This species is not rare but is difficult to collect because of its arboreal habits and seasonal activity peaks.

Treatment of acute schizophrenia with paliperidone ER: predictors for treatment response and benzodiazepine use.

The Paliperidone ER Treatment in Acute Intervention (PERTAIN) study was designed to explore treatment response, tolerability, and safety of flexible doses of paliperidone ER in patients with schizophrenia admitted for an acute exacerbation. This paper addresses a secondary analysis of PERTAIN data designed to explore predictors for treatment response, flexible dosing, and concomitant benzodiazepine use. This prospective, multicenter, phase 3b, open-label, single-arm, 6-week study used flexible doses of paliperidone ER (3 to 12mg once daily) to treat patients hospitalized for an acute exacerbation of schizophrenia, reflecting more closely daily clinical practice. Predictive models were evaluated for paliperidone ER flexible dosing, treatment response, and concomitant treatment with benzodiazepines as distinct independent variables. For the analysis of explanatory variables, a stepwise logistic regression was used, taking into account patient age, gender, body mass index, diagnosis and duration of schizophrenia, number of prior hospitalizations, psychotic symptoms (PANSS), disease severity (CGI-S), and patient functioning (PSP) at baseline. Early response (defined as response within 2weeks of treatment initiation) was also used as a predictor. Clinical response (defined as ≥30% decrease in PANSS total score and ≥1 point decrease in CGI-S from baseline to endpoint) was predicted by early clinical response (p<0.001) and there was a trend for the diagnosis of paranoid schizophrenia vs. other types of schizophrenia to predict clinical response (p=0.0525). High response (defined as ≥50% decrease in PANSS total score and ≥2 points decrease in CGI-S from baseline to endpoint) was predicted by early high response, higher baseline CGI-S, or female gender. More severely ill patients with a higher baseline CGI-S were twice likely to be treated concomitantly with a benzodiazepine.

The science of exoplanets and their systems.

A scientific forum on "The Future Science of Exoplanets and Their Systems," sponsored by Europlanet and the International Space Science Institute (ISSI) and co-organized by the Center for Space and Habitability (CSH) of the University of Bern, was held during December 5 and 6, 2012, in Bern, Switzerland. It gathered 24 well-known specialists in exoplanetary, Solar System, and stellar science to discuss the future of the fast-expanding field of exoplanetary research, which now has nearly 1000 objects to analyze and compare and will develop even more quickly over the coming years. The forum discussions included a review of current observational knowledge, efforts for exoplanetary atmosphere characterization and their formation, water formation, atmospheric evolution, habitability aspects, and our understanding of how exoplanets interact with their stellar and galactic environment throughout their history. Several important and timely research areas of focus for further research efforts in the field were identified by the forum participants. These scientific topics are related to the origin and formation of water and its delivery to planetary bodies and the role of the disk in relation to planet formation, including constraints from observations as well as star-planet interaction processes and their consequences for atmosphere-magnetosphere environments, evolution, and habitability. The relevance of these research areas is outlined in this report, and possible themes for future ISSI workshops are identified that may be proposed by the international research community over the coming 2-3 years.

A new species of the genus Pristimantis (Amphibia, Craugastoridae) associated with the moderately elevated massifs of French Guiana.

We describe a new Pristimantis from French Guiana, northern South America, which is mainly distinguished from known phenotypically related congeners (i.e. species from the polyphyletic unistrigatus species group) occurring at low and middle elevations in the Guiana Shield by the combination of a distinct tympanum, a lower ratio of tibia vs. hand length, a reddish groin region, and a distinct advertisement call consisting of clusters of generally four short notes. The new species inhabits pristine primary forests on the slopes of isolated massifs reaching more than 400 m elevation, and seems not to occur below ca. 200 m above sea level. Such a sharp altitudinal limit suggests a strong influence of thermal variation on the distribution of the species, and therefore a potential sensitivity to climate change. With only nine isolated populations documented so far, the new species should be prioritized for conservation. Historical climate fluctuations during the Quaternary are likely responsible for the distribution pattern of the new species. 

Selection and characterization of recombinant dromedary antiovalbumin antibody fragments that do not cross-react with ovalbumin-related protein X: use for immunoaffinity.

Ovalbumin-related protein X (OVAX) and ovalbumin are two very close ovalbumin-related serpins. As primary data on OVAX remain recent, information about possible cross-reaction of available antiovalbumin antibodies with OVAX is still missing. Using labeled purified OVAX and dot ligand blotting, we identified 49 recombinant dromedary antiovalbumin single domain antibody (sdAb) fragments that were unable to bind OVAX. Discrimination between OVAX and ovalbumin was confirmed for two of the corresponding sdAb fragments by surface plasmon resonance and Western ligand blotting (WLB) characterizations. Furthermore, they were covalently linked to Sepharose and used as an affinity matrix for ovalbumin depletion. At least 90% of the original ovalbumin was eliminated from the allantoic fluid of 14 day old chicken embryo in one step. These sdAb fragments, which bind ovalbumin with nanomolar affinity, should also contribute to a better characterization of ovalbumin preparations.

Lenalidomide in lower-risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis-stimulating agents.

Lenalidomide (LEN) has been shown to yield red blood cell (RBC) transfusion independence in about 25% of lower risk myelodysplastic syndromes (MDS) without del(5q), but its efficacy in patients clearly refractory to erythropoiesis-stimulating agents (ESA) is not known. We report on 31 consecutive lower-risk non-del(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion-dependent (RBC-TD) patients, who became transfusion-independent (RBC-TI). Nine of the responders relapsed, whereas 6 (40%) were still responding and transfusion-free after 11(+)-31(+) months. Median response duration was 24 months. The erythroid response rate was lower in refractory cytopenia with multilineage dysplasia (27% vs. 60%) and tended to be higher in patients treated with LEN + ESA (55% vs. 36%). Response duration was significantly longer in responders who obtained RBC-TI and in patients treated with LEN after primary resistance to ESA. The main toxicity of LEN was cytopenias. We confirm that, in a patient population of lower risk MDS without del 5q clearly resistant to ESA, LEN is an interesting second line therapeutic option. Its combination with ESAs in this context warrants prospective studies.

Systematic donor blood qualification by flow cytometry would have been able to avoid CLL-type MBL transmission after unrelated hematopoietic stem cell transplantation.

The current screening for eligibility of unrelated volunteer marrow donors comprises a complete clinical check-up, a blood CBC and serum protein immunoelectrophoresis. This allows to eliminate acute leukemias, myeloproliferative and myelodysplastic disorders, myelomas and MGUS. To date, the risk of transmission of chronic lymphocytic leukemia (CLL) disease is only evaluated by the clinical evaluation and CBC. We report here the case of a CLL-type MBL disease occurring in a 12-year-old boy after unrelated BMT. Deep biological investigations, as Immunophenotyping, cytogenetic and molecular biology allow us to determine the donor origin of the CLL clone. In 2010, 14.2% donor (105/737) for unrelated hematopoietic stem cell transplantation were over 45y. It is currently estimated (USA) that 1 in 210 men and women will be diagnosed with CLL during their lifetime. Given the long asymptomatic phase of CLL, this raises the case for a detection strategy analog to that used for MGUS and myeloma through serum protein electrophoresis. This case-report, to our knowledge, of a CLL-type MBL unrelated donor-to-recipient transmission through BMT raises ethical and practical questions, such as the proper information about disease transmission risk. The cost-effectiveness of a systematic peripheral blood Immunophenotyping in donors elder than 40y at time of stem cell donation should be evaluated.

Treatment with lenalidomide does not appear to increase the risk of progression in lower risk myelodysplastic syndromes with 5q deletion. A comparative analysis by the Groupe Francophone des Myelodysplasies.

BACKGROUND: Although lenalidomide is very effective in the treatment of anemia of lower risk myelodysplastic syndromes with 5q deletion (del 5q), concerns have been raised over the fact that this drug could trigger progression to acute myeloid leukemia in some patients. DESIGN AND METHODS: Ninety-five transfusion-dependent patients with lower risk myelodysplastic syndromes with del 5q were treated with lenalidomide (10 mg/day, for 3 weeks every 4 weeks); six (6.3%) of the patients progressed to acute myeloid leukemia. This cohort of 95 lenalidomide-treated patients was compared to a historical control cohort of 99 patients with lower risk myelodysplastic syndromes with del 5q who never received lenalidomide, using a propensity score approach that can control for potential confounders in non-randomized comparisons. RESULTS: The 4-year estimated cumulative incidence of leukemia was 9% in patients treated with lenalidomide and 15.8% in controls who did not receive lenalidomide (P=0.16). CONCLUSIONS: Using a propensity score approach, we found no significant difference in acute myeloid leukemia progression and survival from diagnosis between the cohort treated with lenalidomide and the control cohort.

Treatment by Lenalidomide in lower risk myelodysplastic syndrome with 5q deletion--the GFM experience.

We treated 95 RBC transfusion dependent lower risk MDS with del 5q with Lenalidomide (10mg/day, 3 weeks/4 weeks). Median age was 70.4, median interval from diagnosis 29 months. IPSS was low in 31% and intermediate-1 in 69% patients. Del 5q was isolated, with 1 additional and >1 additional abnormality in 79%, 14%, and 6% patients, respectively. 62 (65%) patients achieved transfusion independence (TI). The only significant factor predicting TI was baseline platelet count >150 G/L and platelet decrease by at least 50% during the first weeks of treatment (p=0.001). Grade III-IV neutropenia and thrombocytopenia were seen in 74% and 37.9% of the cases, respectively, and 3 deaths were attributed to cytopenias. Eight (8%) patients developed deep venous thrombosis (DVT). Platelet decrease by less than 50% predicted a higher risk of DVT. Only 6 patients (6.3%) patients progressed to AML, but median follow-up time was short (18 months). We confirm the high rate of TI with Lenalidomide in lower risk MDS with del 5q. Very close patient monitoring for cytopenias and DVT is mandatory, especially during the first weeks of treatment.

Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Diffuse large B-cell lymphoma is a common cancer in elderly patients. Although treatment has been standardised in younger patients, no prospective study has been done in patients over 80 years old. We aimed to investigate the efficacy and safety of a decreased dose of CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone) chemotherapy with a conventional dose of rituximab in elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, multicentre, single-arm, phase 2 study of patients aged over 80 years who had diffuse large B-cell lymphoma. Patients were included from 38 centres in France and Belgium. All patients received six cycles of rituximab combined with low-dose CHOP (R-miniCHOP) at 3-week intervals. Patients received 375 mg/m(2) rituximab, 400 mg/m(2) cyclophosphamide, 25 mg/m(2) doxorubicin, and 1 mg vincristine on day 1 of each cycle, and 40 mg/m(2) prednisone on days 1-5. The primary endpoint was overall survival, both unadjusted and adjusted for treatment and baseline prognostic factors. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT01087424. FINDINGS: 150 patients were enrolled between Jan 9, 2006, and Jan 23, 2009 and 149 were included in the intention-to-treat analyses. Median age was 83 years (range 80-95). After a median follow-up of 20 months (range 0-45), the median overall survival was 29 months (95% CI 21 to upper limit not reached); 2-year overall survival was 59% (49-67%). In multivariate analyses, overall survival was only affected by a serum albumin concentration of 35 g/L or less (hazard ratio 3·2, 95% CI 1·4-7·1; p=0·0053). Median progression-free survival was 21 months (95% CI 13 to upper limit not reached), with a 2-year progression free survival of 47% (38-56). 58 deaths were reported, 33 of which were secondary to lymphoma progression. 12 deaths were attributed to toxicity of the treatment. The most frequent side-effect was haematological toxicity (grade ≥3 neutropenia in 59 patients; febrile neutropenia in 11 patients). INTERPRETATION: R-miniCHOP offers a good compromise between efficacy and safety in patients aged over 80 years old. R-miniCHOP should be considered as the new standard treatment in this subgroup of patients. FUNDING: Groupe d'Etude des Lymphomes de l'Adulte (GELA).

Impact of the use of autologous stem cell transplantation at first relapse both in naive and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study.

BACKGROUND: We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. DESIGN AND METHODS: The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42-58%) and 72% (95%CI 64-78%), respectively. RESULTS: The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41-62%) versus 40% (95%CI 24-55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78-97%) versus 63% (95%CI 51-72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. CONCLUSIONS: Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients.

Quality of life after successful treatment of early-stage Hodgkin's lymphoma: 10-year follow-up of the EORTC-GELA H8 randomised controlled trial.

BACKGROUND: Little is known about the longitudinal course of health-related quality of life (HRQoL) in patients with Hodgkin's lymphoma during their post-treatment follow-up and re-adaptation to normal life. We report on the HRQoL of patients treated in the randomised H8 trial of the European Organisation for Research and Treatment of Cancer (EORTC) Lymphoma Group and the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). We aimed to assess HRQoL and fatigue following treatment, to analyse relations with treatment, and to identify factors that predict persistent fatigue. METHODS: Patients received HRQoL questionnaires at the end of primary therapy and during follow-up. The EORTC QLQ-C30 was used to assess HRQoL, and the Multidimensional Fatigue Inventory (MFI-20) was used to assess fatigue. Changes of mean HRQoL scores over time were analysed with mixed models. Multiple polytomic nominal logistic regression was done to identify independent baseline predictors of fatigue within MFI-20 dimensions. Analyses were done on an intention-to-treat basis. This study is registered with www.ClinicalTrials.gov, number NCT00379041. FINDINGS: 2666 assessments from 935 patients were analysed. Mean follow-up was 90 months (range 52-118). Age affected all functioning and symptom scores except emotional functioning, with younger age associated with higher functioning and lower severity of symptoms; improvement with time showed similar patterns between age groups. Women reported lower HRQoL and higher symptom scores than did men. Overall, 3.2% (14/439 for role functioning) to 9.7% (43/442 for social functioning) and 5.8% (29/498 for reduced motivation) to 9.9% (49/498 for general fatigue) of patients reported impairments of 10 points or more (on a 0-100 scale) in QLQ-C30 and MFI-20 scores, respectively, independent of age and sex. Emotional domains were more affected than physical ones. There was no relation between HRQoL outcome and type of treatment. Fatigue (MFI-20 scores) at the end of treatment was the only predictive variable for persistent fatigue, with odds ratios varying from 2.58 (95% CI 1.00-6.67) to 41.51 (12.02-143.33; p

A one-step exclusion-binding procedure for the purification of functional heavy-chain and mammalian-type gamma-globulins from camelid sera.

A new approach has recently been proposed for the purification of 'mammalian-type' IgG, consisting of exclusion binding. The technique uses a gel ('Melon gel'; Pierce) that binds to all plasma proteins, but not to IgGs, thus allowing IgGs to be recovered in the FT (flow-through) fraction. Here, the technique was applied to camelid IgGs, which are known to be composed of not only classic mammalian-type IgGs (IgG1) but also HC-IgGs (heavy chain IgGs). Both mammalian type and HC-IgGs can be purified in the FT fraction of dromedary (Camelus dromedarius) plasma samples with less than 8.5% contamination, by making minor improvements to the conditions recommended by the manufacturer. The contaminant proteins, as determined by LC-MS/MS (liquid chromatography-tandem MS), are mainly transferrin and albumin. The recovery rate is elevated for both types of IgGs (95+/-14% and 88+/-25% for IgG1 and HC-IgGs respectively). IgGs thus purified maintain their ability to bind to their antigen, as measured by surface plasmon resonance and Western ligand blotting. Furthermore, IgGs can be purified from plasma samples of all camelid species in a similar manner, although the ratio of HC-IgGs to total IgGs was lower for Lama (llama) and Vicugna (vicuña) than for Camelus species. The 'Melon gel' technique can thus be used to satisfactorily purify IgG1 and HC-IgGs from all camelid species.

ESSC-ESF position paper--science-driven scenario for space exploration: report from the European Space Sciences Committee (ESSC).

In 2005 the then ESA Directorate for Human Spaceflight, Microgravity and Exploration (D-HME) commissioned a study from the European Science Foundation's (ESF) European Space Sciences Committee (ESSC) to examine the science aspects of the Aurora Programme in preparation for the December 2005 Ministerial Conference of ESA Member States, held in Berlin. A first interim report was presented to ESA at the second stakeholders meeting on 30 and 31 May 2005. A second draft report was made available at the time of the final science stakeholders meeting on 16 September 2005 in order for ESA to use its recommendations to prepare the Executive proposal to the Ministerial Conference. The final ESSC report on that activity came a few months after the Ministerial Conference (June 2006) and attempted to capture some elements of the new situation after Berlin, and in the context of the reduction in NASA's budget that was taking place at that time; e.g., the postponement sine die of the Mars Sample Return mission. At the time of this study, ESSC made it clear to ESA that the timeline imposed prior to the Berlin Conference had not allowed for a proper consultation of the relevant science community and that this should be corrected in the near future. In response to that recommendation, ESSC was asked again in the summer of 2006 to initiate a broad consultation to define a science-driven scenario for the Aurora Programme. This exercise ran between October 2006 and May 2007. ESA provided the funding for staff support, publication costs, and costs related to meetings of a Steering Group, two meetings of a larger ad hoc group (7 and 8 December 2006 and 8 February 2007), and a final scientific workshop on 15 and 16 May 2007 in Athens. As a result of these meetings a draft report was produced and examined by the Ad Hoc Group. Following their endorsement of the report and its approval by the plenary meeting of the ESSC, the draft report was externally refereed, as is now normal practice with all ESSC-ESF reports, and amended accordingly. The Ad Hoc Group defined overarching scientific goals for Europe's exploration programme, dubbed "Emergence and co-evolution of life with its planetary environments," focusing on those targets that can ultimately be reached by humans, i.e., Mars, the Moon, and Near Earth Objects. Mars was further recognized as the focus of that programme, with Mars sample return as the recognized primary goal; furthermore the report clearly states that Europe should position itself as a major actor in defining and leading Mars sample return missions. The report is reproduced in this article. On 26 November 2008 the Ministers of ESA Member States decided to give a high strategic priority to the robotic exploration programme of Mars by funding the enhanced ExoMars mission component, in line therefore with the recommendations from this ESSC-ESF report.

A new method to discriminate immunogen-specific heavy-chain homodimer from heterotetramer immunoglobulin G directly in immunized dromedary whole plasma proteins: Western ligand blotting.

The variable domain of heavy-chain camelid antibodies (VHH), exclusively present in the homodimer IgGs (HC IgG), provides valuable ligands for diagnosis, imaging and therapy. These VHHs are efficiently produced from lymphocytes of immunized animals through phage display and recombination biotechnology. For VHH development it is desirable to identify animals with high affinity HC IgG response by monitoring antigen-binding in the course of immunization. The aim of this study was to propose a direct approach on whole plasma samples to distinguish between homodimer IgG and heterotetramer (IgG(1)) responses, and quantify them, using western ligand blotting (WLB). WLB consists here in electrophoretic separation of the target IgG subclasses on the basis of molecular size and binding of (125)I labeled antigen. First, we established the WLB parameters for titration of antigen-binding homodimers in relation to antigen-binding total IgGs in ovalbumin-immunized dromedary plasma samples and demonstrated that the WLB is an alternative to ELISA for IgG subclass titration. As purification of IgG subclasses or availability of IgG subclass-specific antibodies is not necessary, WLB is more direct and practical for screening a large number of samples. Second, WLB was applied to study the pattern of homodimer and heterotetramer responses during the time-course of immunizations against three different types of immunogens. As these patterns can differ between animals and immunogens, the method may be useful for identifying animals displaying the desired antigen-specific homodimer IgG response. Lastly, WLB was also described in its variant form of dot ligand blotting for identifying antigen-binding phages at the final step of a phage display experiment.

Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease.

BACKGROUND: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. METHODS: From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. RESULTS: The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. CONCLUSIONS: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].).

Underestimation of species richness in neotropical frogs revealed by mtDNA analyses.

BACKGROUND: Amphibians are rapidly vanishing. At the same time, it is most likely that the number of amphibian species is highly underestimated. Recent DNA barcoding work has attempted to define a threshold between intra- and inter-specific genetic distances to help identify candidate species. In groups with high extinction rates and poorly known species boundaries, like amphibians, such tools may provide a way to rapidly evaluate species richness. METHODOLOGY: Here we analyse published and new 16S rDNA sequences from 60 frog species of Amazonia-Guianas to obtain a minimum estimate of the number of undescribed species in this region. We combined isolation by distance, phylogenetic analyses, and comparison of molecular distances to evaluate threshold values for the identification of candidate species among these frogs. PRINCIPAL FINDINGS: In most cases, geographically distant populations belong to genetically highly distinct lineages that could be considered as candidate new species. This was not universal among the taxa studied and thus widespread species of Neotropical frogs really do exist, contrary to previous assumptions. Moreover, the many instances of paraphyly and the wide overlap between distributions of inter- and intra-specific distances reinforce the hypothesis that many cryptic species remain to be described. In our data set, pairwise genetic distances below 0.02 are strongly correlated with geographical distances. This correlation remains statistically significant until genetic distance is 0.05, with no such relation thereafter. This suggests that for higher distances allopatric and sympatric cryptic species prevail. Based on our analyses, we propose a more inclusive pairwise genetic distance of 0.03 between taxa to target lineages that could correspond to candidate species. CONCLUSIONS: Using this approach, we identify 129 candidate species, two-fold greater than the 60 species included in the current study. This leads to estimates of around 170 to 460 frog taxa unrecognized in Amazonia-Guianas. SIGNIFICANCE: As a consequence the global amphibian decline detected especially in the Neotropics may be worse than realised.