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We report here an uncommon case of neonatal acute leukaemia that presented concomitant with serological evidence of rubella infection. The clinical course was aggressive and the patient died 5 days after diagnosis from septicaemia. Leukaemic blasts had a mixed lineage immunophenotype co-expressing a constellation of B-lymphoid (CD19, cytCD22, TdT) and myeloid (CD13, CD33, CD14, anti-MPO) markers, as well as multiple adhesion molecules and markers associated with early lympho-myeloid progenitor cells (CD34, CD7, HLA-DR). A previously unrecorded discordant expression of different CD10 and CD34 epitopes was identified using different monoclonal antibodies. The karyotype was 46,XX t(4;11)(q21;q23) and molecular analysis confirmed rearrangement of the trithorax-related oncogene HRX at 11q23. There was a clonal biallelic rearrangement of the immunoglobulin heavy-chain gene. The features of this rare case have implications for possible aetiological events leading to leukaemia.

Summary Background PD-1 blockade via pembrolizumab monotherapy has shown antitumour activity and toxicity in patients with relapsed or refractory classical Hodgkin lymphoma. Here, we present interim analyses from the KEYNOTE-204 study evaluating pembrolizumab versus brentuximab vedotin for relapsed or refractory classical Hodgkin lymphoma. Methods In this randomised, open-label, phase 3 study, patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma with measurable disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 who were ineligible for or had relapsed after autologous haematopoietic stem-cell transplantation (HSCT) were enrolled at 78 hospitals and cancer centres in 20 countries and territories. Patients were randomly assigned (1:1) with an interactive voice response system to pembrolizumab 200 mg intravenously every 3 weeks or brentuximab vedotin 1·8 mg/kg intravenously every 3 weeks. Randomisation was stratified by previous autologous HSCT and status after front-line therapy. Results from the second interim analysis are presented here, with a database cutoff of Jan 16, 2020. The dual primary endpoints assessed in the intention-to-treat population were progression-free survival as assessed by blinded independent central review, and overall survival (not analysed at this interim analysis). Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT02684292. Recruitment for this trial is closed. Findings Between July 8, 2016, and July 13, 2018, 151 patients were randomly assigned to pembrolizumab and 153 to brentuximab vedotin. After a median time from randomisation to data cutoff of 25·7 months (IQR 23·4–33·0), median progression-free survival was 13·2 months (95% CI 10·9–19·4) for pembrolizumab versus 8·3 months (5·7–8·8) for brentuximab vedotin (hazard ratio 0·65 [95% CI 0·48–0·88]; p=0·0027). The most common grade 3–5 treatment-related adverse events were pneumonitis (six [4%] of 148 patients in the pembrolizumab group vs one [1%] of 152 patients in the brentuximab vedotin group), neutropenia (three [2%] vs 11 [7%]), decreased neutrophil count (one [1%] vs seven [5%]), and peripheral neuropathy (one [1%] vs five [3%]). Serious treatment-related adverse events occurred in 24 (16%) of 148 patients receiving pembrolizumab and 16 (11%) of 152 patients receiving brentuximab vedotin. One treatment-related death due to pneumonia occurred in the pembrolizumab group. Interpretation Pembrolizumab showed statistically significant and clinically meaningful improvement in progression-free survival compared with brentuximab vedotin, with safety consistent with previous reports. These data support pembrolizumab as the preferred treatment option for patients with relapsed or refractory classical Hodgkin lymphoma who have relapsed post-autologous HSCT or are ineligible for autologous HSCT. Funding Merck Sharp & Dohme Corp (a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA). Translation For the Portuguese translation of the Article see Supplementary Materials section.

We investigate the impact of granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (G-PP, N = 83) versus no G-PP (N = 579) on safety and efficacy of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) in the ECHELON-1 study of previously untreated stage III/IV classical Hodgkin lymphoma. G-PP was associated with lower incidence of ≥ grade 3 neutropenia (29% versus 70%) and febrile neutropenia (11% versus 21%). Fewer dose delays (35% versus 49%), reductions (20% versus 26%), and hospitalizations (29% versus 38%) were observed. Seven neutropenia-associated deaths occurred in the A + AVD arm; none received G-PP. A + AVD with G-PP was associated with decreased risk of a modified progression-free survival event by 26% compared with A + AVD alone (95% CI: 0.40–1.37). G-PP reduced the rate and severity of adverse events, including febrile neutropenia, reduced treatment delays, dose reductions, and discontinuations, and may thus improve efficacy outcomes. These data support G-PP for all patients treated with A + AVD.

The origin and the evolution of the universe are concealed in the evanescent diffuse extragalactic background radiation (DEBRA). To reveal these signals, the development of innovative ultra-sensitive bolometers operating in the gigahertz band is required. Here, we review the design and experimental realization of two bias-current-tunable sensors based on one dimensional fully superconducting Josephson junctions: the nanoscale transition edge sensor (nano-TES) and the Josephson escape sensor (JES). In particular, we cover the theoretical basis of the sensors operation, the device fabrication, their experimental electronic and thermal characterization, and the deduced detection performance. Indeed, the nano-TES promises a state-of-the-art noise equivalent power (NEP) of about $5 \times 10^{-20}$ W$/\sqrt{\text{Hz}}$, while the JES is expected to show an unprecedented NEP of the order of $10^{-25}$ W$/\sqrt{\text{Hz}}$. Therefore, the nano-TES and JES are strong candidates to push radio astronomy to the next level., Comment: 14 pages, 5 figures

Terahertz and sub-terahertz band detection has a key role both in fundamental interactions physics and technological applications, such as medical imaging, industrial quality control and homeland security. In particular, transition edge sensors (TESs) and kinetic inductance detectors (KIDs) are the most employed bolometers and calorimeters in the THz and sub-THz band for astrophysics and astroparticles research. Here, we present the electronic, thermal and spectral characterization of an aluminum/copper bilayer sensing structure that, thanks to its thermal properties and a simple miniaturized design, could be considered a perfect candidate to realize an extremely sensitive class of nanoscale TES (nano-TES) for the giga-therahertz band. Indeed, thanks to the reduced dimensionality of the active region and the efficient Andreev mirror (AM) heat confinement, our devices are predicted to reach state-of-the-art TES performance. In particular, as a bolometer the nano-TES is expected to have a noise equivalent power (NEP) of $5\times10^{-20}$ W/$\sqrt{\mathrm{Hz}}$ and a relaxation time of $\sim 10$ ns for the sub-THz band, typical of cosmic microwave background studies. When operated as single-photon sensor, the devices are expected to show a remarkable frequency resolution of 100 GHz, pointing towards the necessary energy sensitivity requested in laboratory axion search experiments. Finally, different multiplexing schemes are proposed and sized for imaging applications., 12 page, 7 figures

INTRODUCTION: Two hundred ten patients with newly diagnosed Hodgkin's lymphoma (HL) were consecutively enrolled in this prospective trial to evaluate the cost-effectiveness of fluorine-18 ((18)F)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scan in initial staging of patients with HL. METHODS: All 210 patients were staged with conventional clinical staging (CCS) methods, including computed tomography (CT), bone marrow biopsy (BMB), and laboratory tests. Patients were also submitted to metabolic staging (MS) with whole-body FDG-PET scan before the beginning of treatment. A standard of reference for staging was determined with all staging procedures, histologic examination, and follow-up examinations. The accuracy of the CCS was compared with the MS. Local unit costs of procedures and tests were evaluated. Incremental cost-effectiveness ratio (ICER) was calculated for both strategies. RESULTS: In the 210 patients with HL, the sensitivity for initial staging of FDG-PET was higher than that of CT and BMB in initial staging (97.9% vs. 87.3%; P < .001 and 94.2% vs. 71.4%, P < 0.003, respectively). The incorporation of FDG-PET in the staging procedure upstaged disease in 50 (24%) patients and downstaged disease in 17 (8%) patients. Changes in treatment would be seen in 32 (15%) patients. Cumulative cost for staging procedures was $3751/patient for CCS compared to $5081 for CCS + PET and $4588 for PET/CT. The ICER of PET/CT strategy was $16,215 per patient with modified treatment. PET/CT costs at the beginning and end of treatment would increase total costs of HL staging and first-line treatment by only 2%. CONCLUSION: FDG-PET is more accurate than CT and BMB in HL staging. Given observed probabilities, FDG-PET is highly cost-effective in the public health care program in Brazil.

The origin of peralkaline silicic rocks is still obscure and stands perhaps as one of the last major unsettled issues in classic igneous petrology. The debate goes back to the end of the 18th century and despite intensive petrological, geochemical and laboratory efforts the consensus has yet to emerge as to which mechanisms produce peralkaline derivatives. Bowen (1937) first proposed that the shift from metaluminous to peralkaline field was due to extensive fractionation of calcic plagioclase. Perhaps the best illustration of such an hypothesis is provided by the Boina rock series in the Ethiopian rift studied by Barberi et al. (1975). However, such an hypothesis still awaits experimental confirmation. A different view has been expressed for the origin of peralkaline rhyolites erupted in the central part of the Kenya Rift Valley. There, a partial melting of crustal protoliths has been advocated on the basis of geochemical arguments (Macdonald et al., 1987). The origin of peralkaline rocks at Pantelleria, the type locality of peralkaline rhyolites, is also a matter of debate. Mahood et al (1990) have proposed an origin via partial melting of Fe-rich differentiates of transitional basalts, whilst Civetta et al. (1998) have argued that pantellerites could be produced via extensive fractionation of their putative parent basalts. The diversity of opinions reflects in part that, presumably, there is not only one mechanism at work. But it is also due to the fact that most experimental studies devoted to the clarification of this problem have failed in producing decisive arguments during more than one century of intense debate.