We present first results from a LOFAR census of non-recycled pulsars. The census includes almost all such pulsars known (194 sources) at declinations Dec > 8° and Galactic latitudes |Gb| > 3°, ...regardless of their expected flux densities and scattering times. Each pulsar was observed for ≥20 min in the contiguous frequency range of 110–188 MHz. Full-Stokes data were recorded. We present the dispersion measures, flux densities, and calibrated total intensity profiles for the 158 pulsars detected in the sample. The median uncertainty in census dispersion measures (1.5 × 10-3 pc cm-3) is ten times smaller, on average, than in the ATNF pulsar catalogue. We combined census flux densities with those in the literature and fitted the resulting broadband spectra with single or broken power-law functions. For 48 census pulsars such fits are being published for the first time. Typically, thechoice between single and broken power-laws, as well as the location of the spectral break, were highly influenced by the spectral coverage of the available flux density measurements. In particular, the inclusion of measurements below 100 MHz appears essential for investigating the low-frequency turnover in the spectra for most of the census pulsars. For several pulsars, we compared the spectral indices from different works and found the typical spread of values to be within 0.5–1.5, suggesting a prevailing underestimation of spectral index errors in the literature. The census observations yielded some unexpected individual source results, as we describe in the paper. Lastly, we will provide this unique sample of wide-band, low-frequency pulse profiles via the European Pulsar Network Database.
Purpose
Diagnostic imaging modalities have moderate sensitivity for the identification of lymph node (LN) metastases in prostate cancer (PCa) patients. Mapping the lymphatic drainage from the ...prostate can help to identify the LNs directly draining from the tumour (sentinel nodes (SNs)); the LNs stated to have the highest chance of containing metastatic cancer cells. Although the lymphatic drainage may differ between segments within the prostate, the location of the primary tumour is not routinely taken into account during peripheral zone-aimed tracer administration. This study evaluates whether linking the SN procedure to the primary cancer deposits increases the identification accuracy of lymphatic metastases.
Methods
Sixty-seven PCa patients, scheduled for robot-assisted laparoscopic prostatectomy (RALP) and extended lymph node dissection (ePLND) with subsequent SN biopsy, were included in this retrospective study. After injection of the hybrid tracer ICG-
99m
Tc-nanocolloid in the prostate, SN mapping was performed based on lymphoscintigraphy and SPECT/CT. SNs were resected using a combination of radio- and fluorescence guidance. Pathology was used to determine the primary tumour location and metastatic spread. Fluorescence imaging of paraffin-embedded prostate tissue was used to determine the location of the tracer deposits in the prostate. This deposition was related to the primary tumour location, the lymphatic drainage pattern of the injected tracer, and the metastatic spread.
Results
In total 265 radioactive LNs (211 SNs and 54 higher-echelon nodes in 64 patients; 4.3 LNs per patient; IQR: 2–6) were identified. In three patients (4%) preoperative imaging did not allow identification of SNs. Tumour-positive SN visualization within the pelvis was shown to be influenced by intraprostatic location of tracer administration. This could be concluded from (1) a clear correlation between lymphatic drainage to the right or left side of the body and tracer deposition on the right or left side of the prostate, (2) visualization of a higher number of LNs after dorsal tracer deposition compared with ventral tracer deposition, (3) different drainage patterns observed for tracer deposition into the base or apex of the prostate, and (4) the indication that intratumoural tracer deposition increases the chance of visualizing nodal metastases compared with extratumoural tracer deposition.
Conclusions
The correlation between the location of the tracer deposits, the location of the primary tumour, and the visualization of the (tumour-positive) SNs indicated that placement of tracer deposits is of influence on the visualized lymphatic drainage pattern. This suggests that tracer injection near or into the primary tumour site is beneficial for the identification of metastatic spread.
Abstract Introduction Conventional sentinel node (SN) mapping is performed by injecting a radiocolloid followed by lymphoscintigraphy (and SPECT/CT imaging). An extra intraoperative injection with ...blue dye can then allow for optical identification of the SN. In order to improve the current clinical standard, the hybrid tracer indocyanine green (ICG)-99m Tc-nanocolloid was introduced, a tracer that is both radioactive and fluorescent. This feasibility study aimed to evaluate the value of a multimodal-based SN biopsy in vulvar cancer. Materials and methods Fifteen patients with vulvar cancer (29 groins) scheduled for SN biopsy were peritumorally injected with ICG-99m Tc-nanocolloid followed by lymphoscintigraphy and SPECT/CT imaging to identify the SNs. In thirteen patients, shortly before the start of the operation, blue dye was intradermally injected around the lesion. SNs were harvested using a combination of radiotracing, fluorescence imaging, and optical blue dye detection. A portable gamma camera was used before and after SN excision to confirm excision of the preoperatively defined SNs. Results Preoperative lymphoscintigraphy and SPECT/CT imaging visualized drainage to 39 SNs in 28 groins. During the operation, 98% ( ex vivo 100%) of the SNs were radioactive. With fluorescence imaging 96% of the SNs ( ex vivo 100%) could be visualized. Only 65% of the SNs had stained blue at the time of excision. Conclusion ICG-99m Tc-nanocolloid can be used for preoperative SN identification and enables multimodal (radioactive and fluorescent) surgical guidance in patients with vulvar cancer. The addition of fluorescence-based optical guidance offers more effective SN visualization compared to blue dye.
Abstract The Green Bank North Celestial Cap survey is one of the largest and most sensitive searches for pulsars and transient radio objects. Observations for the survey have finished; priorities ...have shifted toward long-term monitoring of its discoveries. In this study, we have developed a pipeline to handle large data sets of archival observations and connect them to recent, high-cadence observations taken using the Canadian Hydrogen Intensity Mapping Experiment telescope. This pipeline handles data for 128 pulsars and has produced measurements of spin, positional, and orbital parameters that connect data over observation gaps as large as 2000 days. We have also measured glitches in the timing residuals for five of the pulsars included and proper motion for 19 sources (13 new). We include updates to orbital parameters for 19 pulsars, including nine previously unpublished binaries. For two of these binaries, we provide updated measurements of post-Keplerian binary parameters, which result in much more precise estimates of the total masses of both systems. For PSR J0509+3801, the much improved measurement of the Einstein delay yields much improved mass measurements for the pulsar and its companion, 1.399(6) M ⊙ and 1.412(6) M ⊙ , respectively. For this system, we have also obtained a measurement of the orbital decay due to the emission of gravitational waves, P ̇ B = − 1.37 ( 7 ) × 10 − 12 , which is in agreement with the rate predicted by general relativity for these masses.
We present the discovery of PSR J0250+5854, a radio pulsar with a spin period of 23.5 s. This is the slowest-spinning radio pulsar known. PSR J0250+5854 was discovered by the LOFAR Tied-Array All-Sky ...Survey (LOTAAS), an all-northern-sky survey for pulsars and fast transients at a central observing frequency of 135 MHz. We subsequently detected pulsations from the pulsar in the interferometric images of the LOFAR Two-meter Sky Survey, allowing for subarcsecond localization. This, along with a pre-discovery detection 2 years prior, allowed us to measure the spin-period derivative to be s s−1. The observed spin period derivative of PSR J0250+5854 indicates a surface magnetic field strength, characteristic age, and spindown luminosity of G, 13.7 Myr, and erg s−1, respectively, for a dipolar magnetic field configuration. This also places the pulsar beyond the conventional pulsar death line, where radio emission is expected to cease. The spin period of PSR J0250+5854 is similar to those of the high-energy-emitting magnetars and X-ray dim isolated neutron stars (XDINSs). However, the pulsar was not detected by the Swift/X-Ray Telescope in the energy band of 0.3-10 keV, placing a bolometric luminosity limit of erg s−1 for an assumed cm−2 and a temperature of 85 eV (typical of XDINSs). We discuss the implications of the discovery for models of the pulsar death line as well as the prospect of finding more similarly long-period pulsars, including the advantages provided by LOTAAS for this.
The aim of this study was to assess the superiority of ICG-99mTc-nanocolloid for the intraoperative visual detection of sentinel lymph nodes (SLNs) in vulvar squamous cell carcinoma (VSCC) patients ...compared to standard SLN detection using 99mTc-nanocolloid with blue dye.
In this multicenter, randomized controlled trial, VSCC patients underwent either the standard SLN procedure or with the hybrid tracer ICG-99mTc-nanocolloid. The primary endpoint was the percentage of fluorescent SLNs compared to blue SLNs. Secondary endpoints were successful SLN procedures, surgical outcomes and postoperative complications.
Forty-eight patients were randomized to the standard (n = 24) or fluorescence imaging group (n = 24) using ICG-99mTc-nanocolloid. The percentage of blue SLNs was 65.3% compared to 92.5% fluorescent SLNs (p < 0.001). A successful SLN procedure was obtained in 92.1% of the groins in the standard group and 97.2% of the groins in the fluorescence imaging group (p = 0.33). Groups did not differ in surgical outcome, although more short-term postoperative complications were documented in the standard group (p = 0.041).
Intraoperative visual detection of SLNs in patients with VSCC using ICG-99mTc-nanocolloid was superior compared to 99mTc-nanocolloid and blue dye. The rate of successful SLN procedures between both groups was not significantly different. Fluorescence imaging has potential to be used routinely in the SLN procedure in VSCC patients to facilitate the search by direct visualization.
Clinical Trial Registration: Netherlands Trial Register (Trial ID NL7443).
Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ...ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking.
The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA.
The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment.
Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.
We report on eight millisecond pulsars (MSPs) in binary systems discovered with the Arecibo L-Band Feed Array (PALFA) pulsar survey. Phase-coherent timing solutions derived from 2.5-5 yr of ...observations carried out at the Arecibo and Jodrell Bank observatories are provided. PSR J1921+1929 is a 2.65 ms pulsar in a 39.6 day orbit for which we detect γ-ray pulsations in archival Fermi data. PSR J1928+1245 is a very low-mass-function system with an orbital period of 3.3 hr that belongs to the non-eclipsing black widow population. We also present PSR J1932+1756, the longest-orbital-period (41.5 days) intermediate-mass binary pulsar known to date. In light of the numerous discoveries of binary MSPs over the past years, we characterize the Galactic distribution of known MSP binaries in terms of binary class. Our results support and strengthen previous claims that the scatter in the Galactic scale height distribution correlates inversely with the binary mass function. We provide evidence of observational biases against detecting the most recycled pulsars near the Galactic plane, which overestimates the scale height of lighter systems. A possible bimodality in the mass function of MSPs with massive white dwarfs is also reported.
Pre-targeting is a proven strategy for in vivo delivery of a diagnostic or therapeutic payload. The pre-targeting concept can be realized through various conjugation strategies, one of which is based ...on copper-free "click" chemistry. Copper-free click reactions have shown in vivo potential for imaging and radionuclide therapy, but this conjugation strategy has not yet been explored in combination with microspheres or unicellular organisms. This study aims to evaluate the in vivo efficacy of strain-promoted azide-alkyne cycloaddition (SPAAC) reactions to achieve imaging and targeting of azide-functionalized macro-aggregated albumin (MAA) microspheres and Staphylococcus aureus bacteria.
MAA microspheres (diameter 10-90 μm) were functionalized with a biorthogonal Cy5 fluorophore, bearing an azide functionality (N3), to generate MAA-Cy5-N3. S. aureus (diameter ∼1 μm) were functionalized with 99mTc-UBI29-41-Cy5-N3, generating S. aureus-99mTc-UBI29-41-Cy5-N3. In situ and in vitro click conjugation on the -N3 moieties was studied for 20 h using a radioactivity-based assay and fluorescence microscopy. For in vivo validation, both primary entities, radiolabeled with 99mTc, were deposited into the microvasculature of the liver via intrasplenic injections. Secondary targeting was realized following the intravenous administration of indium-111-radiolabeled diethylenetriaminepentaacetic acid-dibenzocyclooctyne (111In-DTPA-DBCO). To assess click reaction efficiency in vivo, 99mTc and 111In-biodistributions were measured (SPECT and %ID g-1). Use of 111In-DTPA-DBCO in mice without MAA deposits or mice infected with non-functionalized S. aureus served as controls. Ex vivo confocal fluorescence imaging was carried out in excised tissues to confirm the presence of functionalized MAA and bacteria.
In vitro data confirmed effective click reactions on both the MAA particles and the bacterial membrane. SPECT imaging and biodistribution studies revealed significantly (p < 0.05) increased accumulation of 111In-DTPA-DBCO at the sites where MAA-Cy5-N3 (7.5 ± 1.5%ID g-1vs. 3.5 ± 0.5%ID g-1 in control mice) and S. aureus-99mTc-UBI29-41-Cy5-N3 (9.3 ± 1.3%ID g-1vs. 6.0 ± 0.5%ID g-1 in control mice) resided. Ex vivo fluorescence imaging confirmed the presence of either functionalized MAA or S. aureus in excised spleens and livers of mice.
Copper-free click chemistry between a DBCO moiety and Cy5-N3-functionalized microspheres or bacterial entities in the liver can be used to realize in vivo imaging and targeting.
Fast radio bursts (FRBs) are millisecond radio signals that exhibit dispersion larger than what the Galactic electron density can account for. We have conducted a 1446 h survey for FRBs at 145 MHz, ...covering a total of 4193 deg2 on the sky. We used the UK station of the low frequency array (LOFAR) radio telescope – the Rawlings Array – accompanied for a majority of the time by the LOFAR station at Nançay, observing the same fields at the same frequency. Our real-time search backend, Advanced Radio Transient Event Monitor and Identification System – artemis, utilizes graphics processing units to search for pulses with dispersion measures up to 320 cm−3 pc. Previous derived FRB rates from surveys around 1.4 GHz, and favoured FRB interpretations, motivated this survey, despite all previous detections occurring at higher dispersion measures. We detected no new FRBs above a signal-to-noise threshold of 10, leading to the most stringent upper limit yet on the FRB event rate at these frequencies: 29 sky−1 d−1 for five ms-duration pulses above 62 Jy. The non-detection could be due to scatter-broadening, limitations on the volume and time searched, or the shape of FRB flux density spectra. Assuming the latter and that FRBs are standard candles, the non-detection is compatible with the published FRB sky rate, if their spectra follow a power law with frequency (∝ να), with α ≳ +0.1, demonstrating a marked difference from pulsar spectra. Our results suggest that surveys at higher frequencies, including the low frequency component of the Square Kilometre Array, will have better chances to detect, estimate rates and understand the origin and properties of FRBs.
PDF
