We have examined the giant radio galaxy 3C 236 using LOFAR at 143 MHz down to an angular resolution of 7″, in combination with observations at higher frequencies. We used the low frequency data to ...derive spectral index maps with the highest resolution yet at these low frequencies. We confirm a previous detection of an inner hotspot in the north-west lobe and for the first time observe that the south-east lobe hotspot is in fact a triple hotspot, which may point to an intermittent source activity. Also, the spectral index map of 3C 236 shows that the spectral steepening at the inner region of the northern lobe is prominent at low frequencies. The outer regions of both lobes show spectral flattening, in contrast with previous high frequency studies. We derive spectral age estimates for the lobes, as well as particle densities of the IGM at various locations. We propose that the morphological differences between the lobes are driven by variations in the ambient medium density as well as the source activity history.
Abstract
Background and Aim
Chronic thromboembolic pulmonary disease (CTED) is a progressive disease caused by a wall-adherent, fibrotic thrombus in the pulmonary circulation persisting despite oral ...anticoagulation and despite vascular remodeling of the small arteries. Despite normal pulmonary hemodynamics at rest, exercise intolerance and dyspnea have been reported. Drivers and risk factors, as well as the clinical impact of CTED, are not yet adequately characterized. We evaluated clinical factors predictive of the development of postthrombotic pulmonary disease in a cohort of patients with a history of acute pulmonary embolism on oral anticoagulant therapy. We also evaluated its impact on functional capacity, pulmonary haemodinamics at rest and after exercise and right ventricle morphology and function.
Methods
We compared 33 consecutive patients with a history of acute pulmonary embolism and normal pulmonary vascular imaging (group 1, n=16) or persistent defects on perfusion scan (positive P scan) despite therapeutic anticoagulation for 4 months (group 2, n=17), for the following parameters: 1. Thrombotic load (extension of pulmonary thromboembolism on CT angiography) and Pulmonary Embolism Severity Index (PESI) score at the time of admission to the Intensive Care Unit (ICU); 2. Presence of thrombophilia (factor V Leiden, prothrombin variant, lupus anticoagulant); 3. Cardiovascular risk factors; 4. Anthropometric and demographic parameters; 5. Anticoagulation treatment in ICU and at discharge. The two groups of patients were also compared for the World Health Organization functional class (WHO-FC), NT-proBNP, cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and after 24 months.
Results
Compared with group 1, patients with persisting perfusion defects (group 2) featured higher thrombotic load (p=0.004) and PESI score (p=0.02) at the time of ICU admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p<0.001) and ESE (p<0.001). At the 24 months follow-up group 2 showed higher NT-proBNP (p<0.001) and WHO-FC (p<0.001), systolic (p<0.001) and diastolic (p=0.037) right ventricular (RV) dysfunction and worse echo indices of RV-Arterial Coupling (TAPSE/PAPs (p<0.001)), despite maintaining a low or intermediate echocardiographic probability of PH (Table 1).
Conclusions
Despite the low and intermediate echocardiographic probability of PH, patients with persistent positive P scan had reduced functional capacity, and developed ExPH and RV functional deterioration.
We analyzed peripheral blood mononuclear cells (PBMCs) and serum inflammatory biomarkers in patients with mesial temporal lobe epilepsy (drug-resistant - DR, vs. drug-sensitive - DS). Patients with ...epilepsy showed higher levels of serum CCL2, CCL3, IL-8 and AOPP, and lower levels of FRAP and thiols compared to healthy controls (HC). Although none of the serum biomarkers distinguished DR from DS patients, when analysing intracellular cytokines after in vitro stimulation, DR patients presented higher percentages of IL-1β and IL-6 positive monocytes compared to DS patients and HC. Circulating innate immune cells might be implicated in DR epilepsy and constitute potential new targets for treatments.
Immune system molecules are expressed by neurons, yet their functions are often unknown. We have identified IL-13 and its receptor IL-13Ra1 as neuronal, synaptic proteins in mouse, rat, and human ...brains, whose engagement upregulates the phosphorylation of NMDAR and AMPAR subunits and, in turn, increases synaptic activity and CREB-mediated transcription. We demonstrate that increased IL-13 is a hallmark of traumatic brain injury (TBI) in male mice as well as in two distinct cohorts of human patients. We also provide evidence that IL-13 upregulation protects neurons from excitotoxic death. We show IL-13 upregulation occurring in several cohorts of human brain samples and in cerebrospinal fluid (CSF). Thus, IL-13 is a physiological modulator of synaptic physiology of neuronal origin, with implications for the establishment of synaptic plasticity and the survival of neurons under injury conditions. Furthermore, we suggest that the neuroprotection afforded through the upregulation of IL-13 represents an entry point for interventions in the pathophysiology of TBI.
Thoracic endovascular aortic repair of the ascending aorta is becoming an option for patients considered unfit for open surgery. Such an endovascular procedure requires careful pre-operative planning ...and the customization of prosthesis design. The patient-specific tailoring of the procedure may call for dedicated tools to investigate virtual treatment scenarios. Given such considerations, the present study shows a computational framework for choosing and deploying stent-grafts via Finite Element Analysis, by supporting the device sizing and selection in a real case dealing with the endovascular treatment of a pseudoaneurysm. In particular, three devices with various lengths and materials were examined. Two off-the-shelf devices were computationally tested: one composed of Stainless Steel rings with a nominal length of 60 mm and another one with Nitinol rings and a distal free flow extension, with a nominal length of 70 mm. In third place, a custom-made stent-graft, also with Nitinol rings and containing both proximal and distal bare extensions with a nominal length of 75 mm, was deployed. The latter solution based on patient morphology and virtually benchmarked in this simulation framework, enhanced the apposition to the wall by reducing the distance between the skirt and the vessel from more than 6 mm to less than 2 mm in the distal sealing zone. Our experience shows that in-silico simulations can help choosing the right endograft for the ascending aorta as well as the right deployment sequence. This process may also encourage vendors to develop new devices for cases where open repair is unfeasible.
•Stent-graft customization provides better treatment than off-the-shelf devices.•Wall apposition improves when design is tailored with patient-specific simulations.•Realistic simulations necessarily need to resemble the actual deployment sequence.•Virtual tools to support endovascular planning in the aorta are ready to be used.
Abstract
Feedback by radio-loud active galactic nuclei (AGNs) in galaxy groups is not fully understood. Open questions include the duty cycle of the AGN, the spatial extent of the radio lobes, the ...effect they have on the intragroup medium and the fate of the cosmic rays. We present the discovery of a 650 kpc-radio galaxy embedded in steep diffuse emission at z = (0.18793 ± 5) × 10−5 located at the centre of the galaxy group MaxBCG J199.31832+51.72503 using an observation from the LOFAR Two-metre Sky Survey (LoTSS) at the central frequency of 144 MHz. Subsequently, we performed a Giant Meterwave Radio Telescope observation at the central frequency of 607 MHz to study the spectral properties of the source. The observations reveal a radio galaxy with a total radio power Ptot, 1.4 ∼ 2.1 × 1024 W Hz−1, exhibiting two asymmetrical jets and lobes. The derived spectral index map shows a steepening towards the inner regions and a steep-spectrum core region. We model the integrated radio spectrum, providing two possible interpretations: the radio source is evolved but still active or it is just at the end of its active phase. Finally, in the same field of view we have discovered Mpc-sized emission surrounding a close pair of AGN located at a redshift z = (0.0587 ± 2) × 10−4 (SDSS J131544.56+521213.2 and SDSS J131543.99+521055.7) which could be a radio remnant source.
We present the serendipitous detection of the two main OH maser lines at 1667 and 1665 MHz associated with IRAS 10597+5926 at
z
⊙
= 0.19612 in the untargeted Apertif Wide-area Extragalactic imaging ...Survey (AWES), and the subsequent measurement of the OH 1612 MHz satellite line in the same source. With a total OH luminosity of log(
L
/
L
⊙
) = 3.90 ± 0.03, IRAS 10597+5926 is the fourth brightest OH megamaser (OHM) known. We measure a lower limit for the 1667/1612 ratio of
R
1612
> 45.9, which is the highest limiting ratio measured for the 1612 MHz OH satellite line to date. OH satellite line measurements provide a potentially valuable constraint by which to compare detailed models of OH maser pumping mechanisms. Optical imaging shows that the galaxy is likely a late-stage merger. Based on published infrared and far ultraviolet fluxes, we find that the galaxy is an ultra-luminous infrared galaxy (ULIRG) with log(
L
TIR
/
L
⊙
) = 12.24 that is undergoing a starburst with an estimated star formation rate of 179 ± 40
M
⊙
yr
−1
. These host galaxy properties are consistent with the physical conditions responsible for very bright OHM emission. Finally, we provide an update on the predicted number of OH masers that may be found in AWES and estimate the total number of OH masers that will be detected in each of the individual main and satellite OH 18 cm lines.
The propagation of radio waves from distant compact radio sources through turbulent interstellar plasma in our Galaxy causes these sources to twinkle, a phenomenon called interstellar scintillation. ...Such scintillations are a unique probe of the micro-arcsecond structure of radio sources as well as of the sub-AU-scale structure of the Galactic interstellar medium. Weak scintillations (i.e. an intensity modulation of a few percent) on timescales of a few days or longer are commonly seen at centimetre wavelengths and are thought to result from the line-of-sight integrated turbulence in the interstellar plasma of the Milky Way. So far, only three sources were known that show more extreme variations, with modulations at the level of some dozen percent on timescales shorter than an hour. This requires propagation through nearby (
d
≲ 10 pc) anomalously dense (
n
e
∼ 10
2
cm
−3
) plasma clouds. Here we report the discovery with Apertif of a source (J1402+5347) showing extreme (∼50%) and rapid variations on a timescale of just 6.5 min in the decimetre band (1.4 GHz). The spatial scintillation pattern is highly anisotropic, with a semi-minor axis of about 20 000 km. The canonical theory of refractive scintillation constrains the scattering plasma to be within the Oort cloud. The sightline to J1402+5347, however, passes unusually close to the B3 star Alkaid (
η
UMa) at a distance of 32 pc. If the scintillations are associated with Alkaid, then the angular size of J1402+5347 along the minor axis of the scintels must be smaller than ≈10
μ
as, yielding an apparent brightness temperature for an isotropic source of ≳10
14
K.
Antibody-drug conjugates (ADCs) have reshaped the treatment of several malignancies, including breast cancer. Two ADCs are currently approved for the treatment of each breast cancer subtype, ...including the HER2 targeted ADCs trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), and the TROP2-targeted ADC sacituzumab govitecan. Each of the ADC components (antibody, linker, and payload) plays a key role in determining the efficacy and toxicity profile of an individual ADC, and their modification can lead to major changes in the clinical profile of these agents. Leveraging the knowledge from three decades of development in the field, several novel ADCs are currently being investigated. Some approaches include targeting different antigens beyond the established HER2/TROP2, or evaluating innovative constructs, such as bispecific ADCs, ADCs with dual payload, immune-modulating ADCs, radionuclide drug conjugates, and masked ADCs, among others. In this review article we discuss the evolving landscape of novel ADCs, highlighting opportunities and challenges emerging in the field.
•Antibody-drug conjugates (ADCs) have reshaped the treatment of breast cancer.•Three ADCs are approved for the treatment of breast cancer, targeting either HER2 or TROP2.•Given the modular nature of ADCs, modifications in each of their components are being studied to improve their activity and minimize toxicities.•A multiplicity of other surface antigens are being studied as ADC targets.•Promising developments in the field include bispecific ADCs, ADCs with dual payload, immune-modulating ADCs and masked ADCs, among others.
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