Aims.
We mainly aim to search for the lithium depletion boundary (LDB) among the sub-stellar population of the open star cluster Coma Berenices.
Methods.
Since the number of brown dwarf candidates in ...Coma Ber available in the literature is scarce, we carried out a search for additional candidates photometrically using colour–magnitude diagrams combining optical and infrared photometry from the latest public releases of the following large-scale surveys: the United Kingdom InfraRed Telescope Infrared Deep Sky Survey (UKIRT/UKIDSS), the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS), the Sloan Digital Sky Survey (SDSS), and AllWISE. We checked astrometric consistency with cluster membership using
G
a
i
a
DR2. A search for Li in three new and five previously known brown dwarf candidate cluster members was performed via spectroscopic observations using the OSIRIS instrument at the 10.4 m Gran Telescopio de Canarias (GTC).
Results.
A couple dozen new photometric candidate brown dwarfs located inside the tidal radius of Coma Ber are reported, but none of these are significantly fainter and cooler than previously known members. No LiI resonance doublet at 6707.8 Å was detected in any of eight Coma Ber targets in the magnitude range
J
= 15–19 and
G
= 20–23 observed with the GTC. Spectral types and radial velocities were derived from the GTC spectra. These values confirm the cluster membership of four L2–L2.5 dwarfs, two of which are new in the literature.
Conclusions.
The large Li depletion factors found among the four bona fide sub-stellar members in Coma Ber implies that the LDB must be located at spectral type later than L2.5 in this cluster. Using the latest evolutionary models for brown dwarfs, a lower limit of 550 Myr on the cluster age is set. This constraint has been combined with other dating methods to obtain an updated age estimate of 780 ± 230 Myr for the Coma Ber open cluster. Identification of significantly cooler sub-stellar cluster members in Coma Ber awaits the advent of the Euclid wide survey, which should reach a depth of about
J
= 23; this superb sensitivity will make it possible to determine the precise location of the sub-stellar LDB in this cluster and to carry out a complete census of its sub-stellar population.
The seafloor is recognised as a major sink for marine litter. However, studies conducted in this compartment addressing marine litter densities and its interactions with fauna are scarce, mainly due ...to sampling constraints. In this paper, we assess marine litter density, composition and interactions with marine communities and evaluate its relationship with fishing activities at the “Banco de la Concepción” seamount (Canary Islands, Spain). We took advantage of underwater video records taken with a Remotely Operated Towed Vehicle in the framework of the LIFE IP INTEMARES project.
A total of 56 video transects were analysed covering about 9 km with 19 h of video recording. Transects were categorised as high, low, and null fishing effort based on the Vessel Monitoring System (VMS) positional data registered between 2009 and 2017. Litter items were recorded in 70% of the transects with a mean density of 2122 (±2464) items km−2. There were significant differences in litter densities over the three levels of fishing pressure, with a density decrease from stations of high to stations of null fishing pressure.
Regarding categories, plastic was by far the most abundant category found (83.1%), mainly consisting of fishing lines, both monofilaments and entangled longlines. The study of the interactions of marine litter with fauna showed that less than 20% of the items presented an interaction with benthic organisms either by causing or not a visible impact. The sponge Asconema setubalense accounted for more than half (57.4%) of all interactions, but only 5% of all A. setubalense specimens showed physical damage.
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•Seafloor litter was first assessed at the Concepción Seamount.•Plastic, mainly fishing lines, represented 83.1% of the overall litter items.•The density of fishing related items decreases from high to null fishing pressure stations.•No points of litter accumulation were found in any of the 56 surveyed transects.•Less than 20% of the items presented an interaction with benthic organisms.
We found that exposure of mice and rats to male but not female experimenters produces pain inhibition. Male-related stimuli induced a robust physiological stress response that results in ...stress-induced analgesia. This effect could be replicated with T-shirts worn by men, bedding material from gonadally intact and unfamiliar male mammals, and presentation of compounds secreted from the human axilla. Experimenter sex can thus affect apparent baseline responses in behavioral testing.
Results from a phase 2 trial of the TPEx chemotherapy regimen (docetaxel–platinum–cetuximab) showed promising results, with a median overall survival of 14·0 months in first-line recurrent or ...metastatic head and neck squamous-cell carcinoma (HNSCC). We therefore aimed to compare the efficacy and safety of the TPEx regimen with the standard of care EXTREME regimen (platinum–fluorouracil–cetuximab) in this setting.
This was a multicentre, open-label, randomised, phase 2 trial, done in 68 centres (cancer centres, university and general hospitals, and private clinics) in France, Spain, and Germany. Eligible patients were aged 18–70 years with histologically confirmed recurrent or metastatic HNSCC unsuitable for curative treatment; had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1; and had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less. Participants were randomly assigned (1:1) using the TenAlea website by investigators or delegated clinical research associates to the TPEx regimen or the EXTREME regimen, with minimisation by ECOG performance status, type of disease evolution, previous cetuximab treatment, and country. The TPEx regimen consisted of docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both intravenously on day 1, and cetuximab on days 1, 8, and 15 (intravenously 400 mg/m2 on day 1 of cycle 1 and 250 mg/m2 weekly subsequently). Four cycles were repeated every 21 days with systematic granulocyte colony-stimulating factor (G-CSF) support at each cycle. In case of disease control after four cycles, intravenous cetuximab 500 mg/m2 was continued every 2 weeks as maintenance therapy until progression or unacceptable toxicity. The EXTREME regimen consisted of fluorouracil 4000 mg/m2 on day 1–4, cisplatin 100 mg/m2 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on day 1 of cycle 1 and 250 mg/m2 weekly subsequently) all delivered intravenously. Six cycles were delivered every 21 days followed by weekly 250 mg/m2 cetuximab as maintenance therapy in case of disease control. G-CSF support was not mandatory per the protocol in the EXTREME regimen. The primary endpoint was overall survival in the intention-to-treat population; safety was analysed in all patients who received at least one dose of chemotherapy or cetuximab. Enrolment is closed and this is the final analysis. This study is registered at ClinicalTrials.gov, NCT02268695.
Between Oct 10, 2014, and Nov 29, 2017, 541 patients were enrolled and randomly assigned to the two treatment regimens (271 to TPEx, 270 to EXTREME). Two patients in the TPEx group had major deviations in consent forms and were not included in the final analysis. Median follow-up was 34·4 months (IQR 26·6–44·8) in the TPEx group and 30·2 months (25·5–45·3) in the EXTREME group. At data cutoff, 209 patients had died in the TPEx group and 218 had died in the EXTREME group. Overall survival did not differ significantly between the groups (median 14·5 months 95% CI 12·5–15·7 in the TPEx group and 13·4 months 12·2–15·4 in the EXTREME group; hazard ratio 0·89 95% CI 0·74–1·08; p=0·23). 214 (81%) of 263 patients in the TPEx group versus 246 (93%) of 265 patients in the EXTREME group had grade 3 or worse adverse events during chemotherapy (p<0·0001). In the TPEx group, 118 (45%) of 263 patients had at least one serious adverse event versus 143 (54%) of 265 patients in the EXTREME group. 16 patients in the TPEx group and 21 in the EXTREME group died in association with adverse events, including seven patients in each group who had fatal infections (including febrile neutropenia). Eight deaths in the TPEx group and 11 deaths in the EXTREME group were assessed as treatment related, most frequently sepsis or septic shock (four in each treatment group).
Although the trial did not meet its primary endpoint, with no significant improvement in overall survival with TPEx versus EXTREME, the TPEx regimen had a favourable safety profile. The TPEx regimen could provide an alternative to standard of care with the EXTREME regimen in the first-line treatment of patients with recurrent or metastatic HNSCC, especially for those who might not be good candidates for up-front pembrolizumab treatment.
Merck Santé and Chugai Pharma.
The purpose of the study was to assess a large representative sample of cancer patients on distress levels, common psychosocial problems, and awareness and use of psychosocial support services. A ...total of 3095 patients were assessed over a 4-week period with the Brief Symptom Inventory-18 (BSI-18), a common problems checklist, and on awareness and use of psychosocial resources. Full data was available on 2776 patients. On average, patients were 60 years old, Caucasian (78.3%), and middle class. Approximately, half were attending for follow-up care. Types of cancer varied, with the largest groups being breast (23.5%), prostate (16.9%), colorectal (7.5%), and lung (5.8%) cancer patients. Overall, 37.8% of all patients met criteria for general distress in the clinical range. A higher proportion of men met case criteria for somatisation, and more women for depression. There were no gender differences in anxiety or overall distress severity. Minority patients were more likely to be distressed, as were those with lower income, cancers other than prostate, and those currently on active treatment. Lung, pancreatic, head and neck, Hodgkin's disease, and brain cancer patients were the most distressed. Almost half of all patients who met distress criteria had not sought professional psychosocial support nor did they intend to in the future. In conclusion, distress is very common in cancer patients across diagnoses and across the disease trajectory. Many patients who report high levels of distress are not taking advantage of available supportive resources. Barriers to such use, and factors predicting distress and use of psychosocial care, require further exploration.
We have obtained projected rotation velocities (v sub(rot) sin i) of a sample of 19 ultracool dwarfs with spectral types in the interval M6.5-T8 using high-resolution, near-infrared spectra obtained ...with NIRSPEC and the Keck II telescope. Among our targets there are two young brown dwarfs, two likely field stars, and 15 likely brown dwarfs (30-72 M sub(Jup)) in the solar neighborhood. Our results indicate that the T-type dwarfs are fast rotators in marked contrast to M-type stars. We have derived v sub(rot) sin i velocities between ,15 and 40 km s super(-1) for them and have found no clear evidence for T dwarfs rotating strongly faster than L dwarfs. However, there is a hint for an increasing lower envelope on moving from mid-M to L spectral types in the v sub(rot)sin i-spectral-type diagram that was previously reported in the literature; our v sub(rot) sin i results extend it to even cooler types. Assuming that field brown dwarfs have a size of 0.08-0.1 R , we can place an upper limit of 12.5 hr on the equatorial rotation period of T-type brown dwarfs. In addition, we have compared our v sub(rot) sin i measurements to spectroscopic rotational velocities of very young brown dwarfs of similar mass available in the literature. The comparison, although model dependent, suggests that brown dwarfs lose some angular momentum during their contraction; however, their spin-down time seems to be significantly longer than that of solar-type to early M stars.
We present 27 new L subdwarfs and classify five of them as esdL and 22 as sdL. Our L subdwarf candidates were selected with the UKIRT Infrared Deep Sky Survey and Sloan Digital Sky Survey. ...Spectroscopic follow-up was carried out primarily with the OSIRIS spectrograph on the Gran Telescopio Canarias. Some of these new objects were followed up with the X-shooter instrument on the Very Large Telescope. We studied the photometric properties of the population of known L subdwarfs using colour-spectral type diagrams and colour-colour diagrams, by comparison with L dwarfs and main sequence stars, and identified new colour spaces for L subdwarf selection/study in current and future surveys. We further discussed the brown dwarf transition-zone and the observational stellar/substellar boundary. We found that about one-third of 66 known L subdwarfs are substellar objects, with two-thirds being very low-mass stars. We also present the Hertzsprung-Russell diagrams, spectral type-absolute magnitude corrections, and tangential velocities of 20 known L subdwarfs observed by the Gaia astrometry satellite. One of our L subdwarf candidates, ULAS J233227.03+123452.0, is a mildly metal-poor spectroscopic binary brown dwarf: a ˜L6p dwarf and a ˜T4p dwarf. This binary is likely a thick disc member according to its kinematics.
Objective: To investigate the neural mechanisms of food motivation in children and adolescents, and examine brain activation differences between healthy weight (HW) and obese participants. Subjects: ...Ten HW children (ages 11–16; BMI < 85%ile) and 10 obese children (ages 10–17; BMI >95%ile) matched for age, gender and years of education. Measurements: Functional magnetic resonance imaging (fMRI) scans were conducted twice: when participants were hungry (pre-meal) and immediately after a standardized meal (post-meal). During the fMRI scans, the participants passively viewed blocked images of food, non-food (animals) and blurred baseline control. Results: Both groups of children showed brain activation to food images in the limbic and paralimbic regions (PFC/OFC). The obese group showed significantly greater activation to food pictures in the PFC (pre-meal) and OFC (post-meal) than the HW group. In addition, the obese group showed less post-meal reduction of activation (vs pre-meal) in the PFC, limbic and the reward-processing regions, including the nucleus accumbens. Conclusion: Limbic and paralimbic activation in high food motivation states was noted in both groups of participants. However, obese children were hyper-responsive to food stimuli as compared with HW children. In addition, unlike HW children, brain activations in response to food stimuli in obese children failed to diminish significantly after eating. This study provides initial evidence that obesity, even among children, is associated with abnormalities in neural networks involved in food motivation, and that the origins of neural circuitry dysfunction associated with obesity may begin early in life.
Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, ...and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery.
In the past three decades, local search has grown from a simple heuristic idea into a mature field of research in combinatorial optimization that is attracting ever-increasing attention. Local search ...is still the method of choice for NP-hard problems as it provides a robust approach for obtaining high-quality solutions to problems of a realistic size in reasonable time. Local Search in Combinatorial Optimization covers local search and its variants from both a theoretical and practical point of view, each topic discussed by a leading authority. This book is an important reference and invaluable source of inspiration for students and researchers in discrete mathematics, computer science, operations research, industrial engineering, and management science. In addition to the editors, the contributors are Mihalis Yannakakis, Craig A. Tovey, Jan H. M. Korst, Peter J. M. van Laarhoven, Alain Hertz, Eric Taillard, Dominique de Werra, Heinz Mühlenbein, Carsten Peterson, Bo Söderberg, David S. Johnson, Lyle A. McGeoch, Michel Gendreau, Gilbert Laporte, Jean-Yves Potvin, Gerard A. P. Kindervater, Martin W. P. Savelsbergh, Edward J. Anderson, Celia A. Glass, Chris N. Potts, C. L. Liu, Peichen Pan, Iiro Honkala, and Patric R. J. Östergård.
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