Bipolar HII regions - Morphology and star formation in their vicinity - I - G319.88++00.79 and G010.32−-00.15

Our goal is to identify bipolar HII regions and to understand their morphology, their evolution, and the role they play in the formation of new generations of stars. We use the Spitzer and Herschel Hi-GAL surveys to identify bipolar HII regions. We search for their exciting star(s) and estimate their distances using near-IR data. Dense clumps are detected using Herschel-SPIRE data. MALT90 observations allow us to ascertain their association with the central HII region. We identify Class 0/I YSOs using their Spitzer and Herschel-PACS emissions. These methods will be applied to the entire sample of candidate bipolar HII regions. This paper focuses on two bipolar HII regions, one interesting in terms of its morphology, G319.88$+$00.79, and one in terms of its star formation, G010.32$-$00.15. Their exciting clusters are identified and their photometric distances estimated to be 2.6 kpc and 1.75 kpc, respectively. We suggest that these regions formed in dense and flat structures that contain filaments. They have a central ionized region and ionized lobes perpendicular to the parental cloud. The remains of the parental cloud appear as dense (more than 10^4 per cm^3) and cold (14-17 K) condensations. The dust in the PDR is warm (19-25 K). Dense massive clumps are present around the central ionized region. G010.32-00.14 is especially remarkable because five clumps of several hundred solar masses surround the central HII region; their peak column density is a few 10^23 per cm^2, and the mean density in their central regions reaches several 10^5 per cm^3. Four of them contain at least one massive YSO; these clumps also contain extended green objects and Class II methanol masers. This morphology suggests that the formation of a second generation of massive stars has been triggered by the central bipolar HII region. It occurs in the compressed material of the parental cloud.Comment: 32 pages, 28 figures, to be published in A&

Refining the properties of the TOI-178 system with CHEOPS and TESS

Context. The TOI-178 system consists of a nearby late K-dwarf transited by six planets in the super-Earth to mini-Neptune regime, with radii ranging from ~1.1 to 2.9 R⊕ and orbital periods between 1.9 and 20.7 days. All planets but the innermost one form a chain of Laplace resonances. Mass estimates derived from a preliminary radial velocity (RV) dataset suggest that the planetary densities do not decrease in a monotonic way with the orbital distance to the star, contrary to what one would expect based on simple formation and evolution models. Aims. To improve the characterisation of this key system and prepare for future studies (in particular with JWST), we performed a detailed photometric study based on 40 new CHEOPS visits, one new TESS sector, and previously published CHEOPS, TESS, and NGTS data. Methods. First we updated the parameters of the host star using the new parallax from Gaia EDR3. We then performed a global analysis of the 100 transits contained in our data to refine the physical and orbital parameters of the six planets and study their transit timing variations (TTVs). We also used our extensive dataset to place constraints on the radii and orbital periods of potential additional transiting planets in the system. Results. Our analysis significantly refines the transit parameters of the six planets, most notably their radii, for which we now obtain relative precisions of ≲3%, with the exception of the smallest planet, b, for which the precision is 5.1%. Combined with the RV mass estimates, the measured TTVs allow us to constrain the eccentricities of planets c to g, which are found to be all below 0.02, as expected from stability requirements. Taken alone, the TTVs also suggest a higher mass for planet d than that estimated from the RVs, which had been found to yield a surprisingly low density for this planet. However, the masses derived from the current TTV dataset are very prior-dependent, and further observations, over a longer temporal baseline, are needed to deepen our understanding of this iconic planetary system

Mental Distress Under Occupation: The Journal of Madeleine Blaess

Madeleine Blaess a British doctoral student studying at the Sorbonne was trapped in Paris unable to return home to York for the duration of the Occupation. In October 1940 she began a diary which she kept diligently until September 1944. This unique testimony written from the perspective of a British student at liberty to roam wartime Paris, focuses more on the civilian struggle through the everyday than on the political and military situation which Blaess, vulnerable to arrest, thinks wise to mention as little as possible. This exhaustively documented, voluminous record of the minutiae of a daily struggle with material hardship discloses a struggle with mental illness articulated and managed through the writing of the diary. That diaries can have a therapeutic purpose for writers under mental strain is axiomatic and this article examines a variety of palliative strategies both deliberate and involuntary invoked through the writing process. In so doing, the article will survey the incidence and causes of civilian mental distress on the home front over the period; an area of inquiry which, other than recent work into the psychological impact of Allied bombing of civilians, has been largely neglected in recent work foregrounding and valorising the historical importance of life-writing sources in the field of Occupation studies

Efficacy and safety of weekly carfilzomib (70 mg/m2), dexamethasone, and daratumumab (KdD70) is comparable to twice-weekly KdD56 while being a more convenient dosing option : a cross-study comparison of the CANDOR and EQUULEUS studies

The regimen of carfilzomib, daratumumab, and dexamethasone (KdD) shows activity in patients with relapsed/refractory multiple myeloma. KdD at the twice-weekly 56 mg/m carfilzomib dose (KdD56) was used in the randomized phase 3 CANDOR study (NCT03158688), whereas KdD at the once-weekly 70 mg/m carfilzomib dose (KdD70) was used in the phase 1 b EQUULEUS study (NCT01998971). We analyzed efficacy data from comparable CANDOR and EQUULEUS patients using inverse probability of treatment weighting (IPTW)-adjusted models. These weights were calculated from propensity scores derived to balance prespecified baseline covariates. The side-by-side and adjusted comparisons showed similar efficacy for overall response rates and progression-free survival in the two groups, with a series of sensitivity analyses showing consistent findings. Safety data were generally consistent with the known safety profiles of each individual drug. Once-weekly KdD70 is comparable to twice-weekly KdD56 in terms of efficacy and safety while being a more convenient dosing option

Six transiting planets and a chain of Laplace resonances in TOI-178

Determining the architecture of multi-planetary systems is one of the cornerstones of understanding planet formation and evolution. Resonant systems are especially important as the fragility of their orbital configuration ensures that no significant scattering or collisional event has taken place since the earliest formation phase when the parent protoplanetary disc was still present. In this context, TOI-178 has been the subject of particular attention since the first TESS observations hinted at the possible presence of a near 2:3:3 resonant chain. Here we report the results of observations from CHEOPS, ESPRESSO, NGTS, and SPECULOOS with the aim of deciphering the peculiar orbital architecture of the system. We show that TOI-178 harbours at least six planets in the super-Earth to mini-Neptune regimes, with radii ranging from 1.152−0.070+0.073 to 2.87−0.13+0.14 Earth radii and periods of 1.91, 3.24, 6.56, 9.96, 15.23, and 20.71 days. All planets but the innermost one form a 2:4:6:9:12 chain of Laplace resonances, and the planetary densities show important variations from planet to planet, jumping from 1.02−0.23+0.28 to 0.177−0.061+0.055 times the Earth's density between planets c and d. Using Bayesian interior structure retrieval models, we show that the amount of gas in the planets does not vary in a monotonous way, contrary to what one would expect from simple formation and evolution models and unlike other known systems in a chain of Laplace resonances. The brightness of TOI-178 (H = 8.76 mag, J = 9.37 mag, V = 11.95 mag) allows for a precise characterisation of its orbital architecture as well as of the physical nature of the six presently known transiting planets it harbours. The peculiar orbital configuration and the diversity in average density among the planets in the system will enable the study of interior planetary structures and atmospheric evolution, providing important clues on the formation of super-Earths and mini-Neptunes

Multicenter analysis of sputum microbiota in tuberculosis patients.

The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship between M. tuberculosis pulmonary infection and the resident lung microbiota remains vague. In this work we describe the results obtained from a multicenter study of the microbiota of sputum samples from patients with tuberculosis or unrelated lung diseases and healthy donors recruited in Switzerland, Italy and Bangladesh, with the ultimate goal of discovering a microbiota-based biomarker associated with tuberculosis. Bacterial 16S rDNA amplification, high-throughput sequencing and extensive bioinformatic analyses revealed patient-specific flora and high variability in taxon abundance. No common signature could be identified among the individuals enrolled except for minor differences which were not consistent among the different geographical settings. Moreover, anti-tuberculosis therapy did not cause any important variation in microbiota diversity, thus precluding its exploitation as a biomarker for the follow up of tuberculosis patients undergoing treatment

Evidence for transit-timing variations of the 11 Myr exoplanet TOI-1227 b

TOI-1227 b is an 11 Myr old validated transiting planet in the middle of its contraction phase, with a current radius of 0.85 RJ. It orbits a low-mass pre-main sequence star (0.170 M⊙, 0.56 R⊙) every 27.4 days. The magnetic activity of its young host star induces radial velocity jitter and prevents good measurements of the planetary mass. We gathered additional transit observations of TOI-1227 b with space- and ground-based telescopes, and we detected highly significant transit-timing variations (TTVs). Their amplitude is about 40 minutes and their dominant timescale is longer than 3.7 years. Their most probable origin is dynamical interactions with additional planets in the system. We modeled the TTVs with inner and outer perturbers near first and second order resonances; several orbital configurations provide an acceptable fit. More data are needed to determine the actual orbital configuration and eventually measure the planetary masses. These TTVs and an updated transit chromaticity analysis reinforce the evidence that TOI-1227 b is a planet

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m(2) on days 1 and 2 of cycle 1; 27 mg/m(2) thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

Background Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. Methods In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. Results A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%). Conclusions A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.