Abstract
We present the full panchromatic afterglow light-curve data of GW170817, including new radio data as well as archival optical and X-ray data, between 0.5 and 940 days post-merger. By ...compiling all archival data and reprocessing a subset of it, we have evaluated the impact of differences in data processing or flux determination methods used by different groups and attempted to mitigate these differences to provide a more uniform data set. Simple power-law fits to the uniform afterglow light curve indicate a
t
0.86±0.04
rise, a
t
−1.92±0.12
decline, and a peak occurring at 155 ± 4 days. The afterglow is optically thin throughout its evolution, consistent with a single spectral index (−0.584 ± 0.002) across all epochs. This gives a precise and updated estimate of the electron power-law index,
p
= 2.168 ± 0.004. By studying the diffuse X-ray emission from the host galaxy, we place a conservative upper limit on the hot ionized interstellar medium density, <0.01 cm
−3
, consistent with previous afterglow studies. Using the late-time afterglow data we rule out any long-lived neutron star remnant having a magnetic field strength between 10
10.4
and 10
16
G. Our fits to the afterglow data using an analytical model that includes Very Long Baseline Interferometry proper motion from Mooley et al., and a structured jet model that ignores the proper motion, indicates that the proper-motion measurement needs to be considered when seeking an accurate estimate of the viewing angle.
Highlights • Prenatal dexamethasone increased anxiety- and despair- like behaviors in females. • Prenatal dexamethasone increased TpH2 mRNA in female caudal DRN at P7. • Prenatal dexamethasone ...decreased TpH2 mRNA in female caudal DRN in adulthood. • Stress-challenged females with prenatal dexamethasone had lower TpH2 in rostral DRN. • All prenatal dexamethasone effects were found selectively in females but not males.
Giant Pairing Vibrations in light nuclei Cavallaro, M.; Cappuzzello, F.; Carbone, D. ...
The European physical journal. A, Hadrons and nuclei,
12/2019, Letnik:
55, Številka:
12
Journal Article
Recenzirano
.
Signatures of the population of the Giant Pairing Vibration (GPV), a correlated two-nucleon excitation across major shell expected to be populated in two-nucleon transfer reactions, have been ...observed for the first time in carbon isotopes. In the present paper, a review of the experimental methods and of the analysis leading to that observation is reported. A new case, with new experimental data, regarding the possible population of the GPV in another light nucleus,
11
Be , by the same reaction, is introduced and discussed.
To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA ...trial with a 2-year minimum follow-up.
Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs.
With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months hazard ratio 0.72 (95% confidence interval 0.61-0.86); 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation.
With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.
•Nivolumab + ipilimumab + two cycles of chemotherapy (chemo) significantly prolonged survival versus chemo in first-line advanced NSCLC.•At 2 years, overall survival benefits were durable with nivolumab + ipilimumab + chemo versus chemo.•Benefits of nivolumab + ipilimumab + chemo were seen across most patient subgroups, including by PD-L1 and histology.•Discontinuing nivolumab + ipilimumab + chemo due to treatment-related AEs did not negatively impact long-term benefits.•Nivolumab + ipilimumab + two cycles of chemo is an efficacious first-line treatment option for advanced non-oncogene-driven NSCLC.
In utero exposure to glucocorticoids in late gestation programs changes in cardiovascular function. The objective of this study was to determine the degree to which angiotensin II mediates sex-biased ...changes in autonomic function as well as basal and stress-responsive cardiovascular function following in utero glucocorticoid exposure. Pregnant rats were administered the synthetic glucocorticoid dexamethasone (Dex; 0.4 mg/kg/day sc) or vehicle on
. Mean arterial pressure, heart rate, and heart rate variability (HRV) were measured via radiotelemetry in freely moving, conscious adult rats. To evaluate the impact of stress, rats were placed in a restraint tube for 20 min. In a separate cohort of rats, restraint stress was performed before and after chronic treatment with the angiotensin type 1 receptor antagonist, losartan (30 mg/kg/day ip). Frequency domain analysis of HRV was evaluated, and data were integrated into low-frequency (LF, 0.20-0.75 Hz) and high-frequency (HF, 0.75-2.00 Hz) bands. Prenatal Dex resulted in an exaggerated pressor and heart rate response to restraint in female offspring that was attenuated by prior losartan treatment. HF power was higher in vehicle-exposed female rats compared with Dex females. Following losartan, HF power was equivalent between female vehicle and Dex-exposed rats. In utero exposure to Dex produced female-biased alterations in stress-responsive cardiovascular function, which may be indicative of a reduction in parasympathetic activity. Moreover, these findings suggest this autonomic dysregulation may be mediated, in part, by long-term changes in renin-angiotensin signaling.
Our findings reveal the involvement of angiotensin II on sex-selective cardiovascular function and autonomic changes in adult offspring exposed to dexamethasone during the last 4 days of gestation. We show that angiotensin II receptor blockade reverses the exaggerated pressor and heart rate response to acute restraint stress and the autonomic dysregulation observed in female, but not male, offspring exposed to dexamethasone in utero.
Notch signaling is a highly conserved pathway important for normal embryonic development and cancer. We previously demonstrated a role for Notch3 in lung cancer pathogenesis. Notch3 inhibition ...resulted in tumor apoptosis and growth suppression. In vitro, these effects were enhanced when the epidermal growth factor receptor (EGFR) pathway was also inhibited, suggesting significant cross-talk between the two pathways. How Notch3 and epidermal growth factor receptor-mitogen-activated protein kinase (EGFR-MAPK) pathways cooperate in modulating apoptosis is not yet known. In this study, we provide evidence that Notch3 regulates Bim, a BH-3-only protein, via MAPK signaling. Furthermore, loss of Bim expression prevents tumor apoptosis induced by Notch3 inhibition. Using gamma-secretase inhibitor and erlotinib in a xenograft model, Bim induction and tumor inhibition were observed to be enhanced compared with either agent alone, consistent with our previous observation of significant synergism between Notch and EGFR-ras-MAPK signaling. Thus, our data support the hypothesis that Notch3 not only has a crucial role in lung cancer through regulating apoptosis, but also cooperates with the EGFR-MAPK pathway in modulating Bim.
•Advanced NSCLC patients reported moderate/severe depressive symptoms at diagnosis.•Severely depressed patients had the highest suicidality, hopelessness, anxiety, and stress.•Severely depressed ...patients reported the most intense dyspnea, cough, and pain.•Functioning (usual activity/mobility/self-care) was poorest in the severely depressed.•Moderate/severe depressive symptoms co-occur with multiple lung cancer morbidities.
The aims of this observational study were to 1) accrue newly diagnosed patients with advanced-stage non-small cell lung cancer (NSCLC) awaiting the start of first-line treatment and identify those with moderate to severe depressive symptoms and, 2) provide a clinical description of the multiple, co-occurring psychological and behavioral difficulties and physical symptoms that potentially exacerbate and maintain depressive symptoms.
Patients with stage IV NSCLC (N = 186) were enrolled in an observational study (ClinicalTrials.gov Identifier: NCT03199651) and completed the American Society of Clinical Oncology-recommended screening measure for depression (Patient Health Questionnaire-9 PHQ-9). Individuals with none/mild (n = 119; 64 %), moderate (n = 52; 28 %), and severe (n = 15; 8 %) depressive symptoms were identified. Patients also completed measures of hopelessness, generalized anxiety disorder (GAD) symptoms, stress, illness perceptions, functional status, and symptoms.
Patients with severe depressive symptoms reported concomitant feelings of hopelessness (elevating risk for suicidal behavior), anxiety symptoms suggestive of GAD, and traumatic, cancer-specific stress. They perceived lung cancer as consequential for their lives and not controllable with treatment. Pain and multiple severe symptoms were present along with substantial functional impairment. Patients with moderate depressive symptoms had generally lower levels of disturbance, though still substantial. The most salient differences were low GAD symptom severity and fewer functional impairments for those with moderate symptoms.
Depressive symptoms of moderate to severe levels co-occur in a matrix of clinical levels of anxiety symptoms, traumatic stress, impaired functional status, and pain and other physical symptoms. All of the latter factors have been shown, individually and collectively, to contribute to the maintenance or exacerbation of depressive symptoms. As life-extending targeted and immunotherapy use expands, prompt identification of patients with moderate to severe depressive symptoms, referral for evaluation, and psychological/behavioral treatment are key to maximizing treatment outcomes and quality of life for individuals with advanced NSCLC.
Defective dendritic cell (DC) function caused by abnormal differentiation of these cells is an important mechanism of tumor escape from immune system control. Previously, we have demonstrated that ...the number and function of DC were dramatically reduced in cancer patients. This effect was closely associated with accumulation of immature cells (ImC) in peripheral blood. In this study, we investigated the nature and functional role of those ImC. Using flow cytometry, electron microscopy, colony formation assays, and cell differentiation in the presence of different cell growth factors, we have determined that the population of ImC is composed of a small percentage (<2%) of hemopoietic progenitor cells, with all other cells being represented by MHC class I-positive myeloid cells. About one-third of ImC were immature macrophages and DC, and the remaining cells were immature myeloid cells at earlier stages of differentiation. These cells were differentiated into mature DC in the presence of 1 microM all-trans-retinoic acid. Removal of ImC from DC fractions completely restored the ability of the DC to stimulate allogeneic T cells. In two different experimental systems ImC inhibited Ag-specific T cell responses. Thus, immature myeloid cells generated in large numbers in cancer patients are able to directly inhibit Ag-specific T cell responses. This may represent a new mechanism of immune suppression in cancer and may suggest a new approach to cancer treatment.
This is a retrospective case-control study.
To identify predictors of lower extremity (LE) long bone fracture-related amputation in persons with traumatic spinal cord injury (tSCI).
US Veterans ...Health Administration facilities (2005-2015).
Fracture-amputation sets in Veterans with tSCI were considered for inclusion if medical coding indicated a LE amputation within 365 days following an incident LE fracture. The authors adjudicated each fracture-amputation set by electronic health record review. Controls with incident LE fracture and no subsequent amputation were matched 1:1 with fracture-amputation sets on site and date of fracture (±30 days). Multivariable conditional logistic regression determined odds ratios (OR) and 95% confidence intervals (CI) for potential predictors (motor-complete injury; diabetes mellitus (DM); peripheral vascular disease (PVD); smoking; primary (within 30 days) nonsurgical fracture management; pressure injury and/or infection), controlling for age and race.
Forty fracture-amputation sets from 37 Veterans with LE amputations and 40 unique controls were identified. DM (OR = 26; 95% CI, 1.7-382), PVD (OR = 30; 95% CI, 2.5-371), and primary nonsurgical management (OR = 40; 95% CI, 1.5-1,116) were independent predictors of LE fracture-related amputation.
Early and aggressive strategies to prevent DM and PVD in tSCI are needed, as these comorbidities are associated with increased odds of LE fracture-related amputation. Nonsurgical fracture management increased the odds of LE amputation by at least 50%. Further large, prospective studies of fracture management in tSCI are needed to confirm our findings. Physicians and patients should consider the potential increased risk of amputation associated with non-operative management of LE fractures in shared decision making.
The
12
C(
18
O,
16
O)
14
C and
13
C(
18
O,
16
O)
15
C reactions have been explored at 84MeV incident energy and the ejectiles have been detected at forward angles by the MAGNEX spectrometer. Thanks ...to the peculiarities of MAGNEX and to the ray-reconstruction technique, high-resolution spectra up to 22MeV excitation energy and high-quality cross-section angular distributions have been obtained. In the region above the two-neutron emission threshold, unknown wide structures have been observed in both the
14
C and
15
C residual nuclei. A detailed analysis of such resonances identifies them as the long-searched Giant Pairing Vibration. These data represent the first experimental signature of it.
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