Aplicação de técnicas de sensoriamento remoto na investigação do controle do posicionamento do Complexo Carbonatítico Seis Lagos e no estudo do depósito (Nb) laterítico associado (Amazonas, Brasil)

The main goals of this study were to identify geological structures that controlled the emplacement of the Seis Lagos Carbonatite Complex and contribute to the knowledge of the associated deposit, through the delimitation of the lateritic crust, the identification of internal structures and hydrothermal zones, where higher concentrations of Nb and REE may occur. Geophysical techniques, analysis of digital terrain elevation and processing techniques of orbital data were employed. The main regional structure has E-W direction and length of about 400 km. The positioning of the SLCC occurred where it is intersected by structures trending NE-SW and NW-SE. The boundaries of the lateritic crust are largely rectilinear, suggesting brittle structures, that may be the walls of the magma conduct, following open faults and fractures, or faults that affect the body after its crystallization. The main structures affecting the deposit have EW or NNW-SSE direction, controlled the formation of valleys and ridges, and karst processes with basin formation; therefore exerted role during laterization. Clayey zones likely related to hydrothermal processes were identified in four structures.Este estudo teve como objetivos principais identificar as estruturas geológicas que controlaram o posicionamento do Complexo Carbonatítico Seis Lagos, localizado no noroeste do Estado do Amazonas, e contribuir para o conhecimento da geologia do depósito associado, através da delimitação da crosta laterítica e identificação de estruturas internas e de zonas de alteração hidrotermal onde maiores concentrações de Nb e ETR podem ocorrer. Foram utilizados os métodos geofísicos aeromagnetometria, aerogamaespectometria e mapas de anomalia Bouger, análise de modelo digital de elevação e técnicas de processamento de dados orbitais. A principal estrutura regional tem direção geral E-W, extensão de cerca de 400 km. O posicionamento do CCSL ocorreu onde ela é intersectada por estruturas de direção NE-SW e NW-SE. Os limites da crosta laterítica são em grande parte retilíneos, sugerindo estruturas rúpteis, sejam estas as paredes do conduto magmático, aberto seguindo falhas e fraturas, ou falhas que afetaram o corpo após sua cristaliza- ção. As principais estruturas afetando o depósito têm direção E-W ou NNW-SSE, controlaram a formação de vales e cristas, a atuação de processos cársticos com formação de bacias; exerceram, portanto, papel relevante durante o processo de lateritização. Zonas ricas em argilas indicativas de alteração hidrotermal foram identificadas em quatro estruturas

Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity

Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair. We find that loss of Merlin in these cells causes a catastrophic failure of axonal regeneration and remyelination in the PNS. This effect is mediated by activation of YAP expression in Merlin-null SCs, and loss of YAP restores axonal regrowth and functional repair. This work identifies new mechanisms that control the regenerative potential of SCs and gives new insight into understanding the correct control of functional nerve repair in the PNS

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Mineralogy and Geochemistry of Laterites from the Morro dos Seis Lagos Nb (Ti, REE) Deposit (Amazonas, Brazil).

International audienceThe Morro dos Seis Lagos niobium deposit (2897.9 Mt at 2.81 wt.% Nb2O5) is associated with laterites formed by the weathering of siderite carbonatite. This iron-rich lateritic profile (>100 m in thickness) is divided into six textural and compositional types, which from the top to the base of the sequence is: (1) pisolitic laterite, (2) fragmented laterite, (3) mottled laterite, (4) purple laterite, (5) manganiferous laterite, and (6) brown laterite. All the laterites are composed mainly of goethite (predominant in the lower and upper varieties) and hematite (predominant in the intermediate types, formed from goethite dehydroxylation). The upper laterites were reworked, resulting in goethite formation. In the manganiferous laterite (10 m thick), the manganese oxides (mainly hollandite, with associated cerianite) occur as veins or irregular masses, formed in a late event during the development of the lateritic profile, precipitated from a solution with higher oxidation potential than that for Fe oxides, closer to the water table. Siderite is the source for the Mn. The main Nb ore mineral is Nb-rich rutile (with 11.26 – 22.23 wt.% Nb2O5), which occurs in all of the laterites and formed at expense of a former secondary pyrochlore, together with Ce-pyrochlore (last pyrochore before final breakdown), Nb-rich goethite and minor cerianite. The paragenesis results of lateralization have been extremely intense. Minor Nb-rich brookite formed from Nb-rich rutile occurs as broken spherules with an “oolitic” (or Liesegang ring structure). Nb-rich rutile and Nb-rich brookite incorporate Nb following the [Fe3+ + (Nb, Ta) for 2Ti] substitution and both contain up to 2 wt.% WO3. The laterites have an average Nb2O5 content of 2.91 wt.% and average TiO2 5.00 wt.% in the upper parts of the sequence. Average CeO2 concentration increases with increasing depth, from 0.12 wt.% in the pisolitic type to 3.50 wt.% in the brown laterite. HREE concentration is very low