We use the first 100 deg2 of overlap between the Kilo-Degree Survey and the Galaxy And Mass Assembly survey to determine the average galaxy halo mass of ∼10 000 spectroscopically confirmed satellite ...galaxies in massive (M > 1013 h
−1 M⊙) galaxy groups. Separating the sample as a function of projected distance to the group centre, we jointly model the satellites and their host groups with Navarro–Frenk–White density profiles, fully accounting for the data covariance. The probed satellite galaxies in these groups have total masses log 〈M
sub/(h
−1 M⊙)〉 ≈ 11.7–12.2 consistent across group-centric distance within the errorbars. Given their typical stellar masses, log 〈M
⋆, sat/(h
−2 M⊙)〉 ∼ 10.5, such total masses imply stellar mass fractions of 〈M
⋆, sat〉/〈M
sub〉 ≈ 0.04 h
−1. The average subhalo hosting these satellite galaxies has a mass M
sub ∼ 0.015M
host independent of host halo mass, in broad agreement with the expectations of structure formation in a Λ cold dark matter universe.
In patients with metastatic neuroendocrine neoplasms, the liver is the most commonly affected organ and a crucial factor for prognosis and survival. Peptide receptor radionuclide therapy can prolong ...progression-free survival in these patients. Additional treatment of liver disease might further improve outcomes. We aimed to investigate the safety and efficacy of additional holmium-166 (166Ho) radioembolisation after peptide receptor radionuclide therapy in patients with metastatic liver neuroendocrine neoplasms.
The Holmium Embolization Particles for Arterial Radiotherapy Plus 177Lu-Dotatate in Salvage Neuroendocrine Tumour Patients (HEPAR PLuS) study was a single-centre, phase 2 study done at the University Medical Center Utrecht (Utrecht, Netherlands). Patients, aged at least 18 years, with histologically proven grade 1 or 2 neuroendocrine neoplasms of all origins, an Eastern Cooperative Oncology Group performance status of 0–2, and three or more measurable liver metastases according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria received 166Ho-radioembolisation within 20 weeks after four cycles of peptide receptor radionuclide therapy (lutetium-177-dotatate 177Lu-dotatate). The primary endpoint was objective liver tumour response in the treated liver volume, defined as complete response (disappearance of all lesions) or partial response (≥30% decrease in the sum of the longest diameters of the target lesions, compared with baseline measurements), according to RECIST 1.1, analysed per protocol at 3 months. Safety was assessed in all patients who received treatment. This study is registered with ClinicalTrials.gov, NCT02067988. Recruitment is completed and long-term follow-up is ongoing.
From Oct 15, 2014, to Sept 12, 2018, 34 patients were assessed for eligibility. 31 patients received treatment and 30 (97%) patients were available for primary endpoint assessment and completed 6 months of follow-up. Three (9%) patients were excluded at screening and one (3%) patient was treated and died before the primary endpoint and was replaced. According to the per-protocol analysis 13 (43%; 95% CI 26–63) of 30 patients achieved an objective response in the treated volume. The most frequently reported Common Terminology Criteria for Adverse Events (CTCAE) grade 3–4 clinical and laboratory toxicities within 6 months included abdominal pain (three 10% of 31 patients), increased γ-glutamyl transpeptidase (16 54%), and lymphocytopenia (seven 23%). One (3%) fatal treatment-related serious adverse event occurred (radioembolisation-induced liver disease). Two (6%) patients had serious adverse events deemed to be unrelated to treatment (gastric ulcer and perforated cholecystitis).
166Ho-radioembolisation, as an adjunct to peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm liver metastases, is safe and efficacious. Radioembolisation can be considered in patients with bulky liver disease, including after peptide receptor radionuclide therapy. A future randomised, controlled study should investigate the added benefit of this treatment on progression-free survival.
None.
We announce the discovery of a new dwarf galaxy, Leo T, in the Local Group. It was found as a stellar overdensity in the Sloan Digital Sky Survey Data Release 5 (SDSS DR5). The color-magnitude ...diagram of Leo T shows two well-defined features, which we interpret as a red giant branch and a sequence of young, massive stars. As judged from fits to the color-magnitude diagram, it lies at a distance of 420 kpc and has an intermediate-age stellar population with a metallicity of Fe/H = -1.6, together with a young population of blue stars of age 200 Myr. There is a compact cloud of neutral hydrogen with mass 10 super(5) M sub( )and radial velocity +35 km s super(-1) coincident with the object visible in the HIPASS channel maps. Leo T is the smallest, lowest luminosity galaxy found to date with recent star formation. It appears to be a transition object similar to, but much lower luminosity than, the Phoenix dwarf.
Abstract
We describe the selection of galaxies targeted in eight low-redshift clusters (APMCC0917, A168, A4038, EDCC442, A3880, A2399, A119 and A85; 0.029 < z < 0.058) as part of the Sydney-AAO ...Multi-Object Integral field spectrograph Galaxy Survey (SAMI-GS). We have conducted a redshift survey of these clusters using the AAOmega multi-object spectrograph on the 3.9-m Anglo-Australian Telescope. The redshift survey is used to determine cluster membership and to characterize the dynamical properties of the clusters. In combination with existing data, the survey resulted in 21 257 reliable redshift measurements and 2899 confirmed cluster member galaxies. Our redshift catalogue has a high spectroscopic completeness (∼94 per cent) for rpetro ≤ 19.4 and cluster-centric distances R < 2R200. We use the confirmed cluster member positions and redshifts to determine cluster velocity dispersion, R200, virial and caustic masses, as well as cluster structure. The clusters have virial masses 14.25 ≤ log(M200/M⊙) ≤ 15.19. The cluster sample exhibits a range of dynamical states, from relatively relaxed-appearing systems, to clusters with strong indications of merger-related substructure. Aperture- and point spread function matched photometry are derived from Sloan Digital Sky Survey and VLT Survey Telescope/ATLAS imaging and used to estimate stellar masses. These estimates, in combination with the redshifts, are used to define the input target catalogue for the cluster portion of the SAMI-GS. The primary SAMI-GS cluster targets have R <R200, velocities |vpec| < 3.5σ200 and stellar masses $9.5 \le {\rm log({\it M}}^*_{{\rm approx}}/$M⊙)≤12. Finally, we give an update on the SAMI-GS progress for the cluster regions.
HIV reservoir quantification is essential for evaluation of HIV curative strategies and may provide valuable insights about reservoir dynamics during antiretroviral therapy. The Intact Proviral DNA ...Assay (IPDA) provides the unique opportunity to quantify the intact and defective reservoir. The current IPDA is optimized for HIV-1 subtype B, the dominant subtype in resource-rich settings. However, subtype C is dominant in Sub-Saharan Africa, jointly accounting for around 60% of the pandemic. We developed an assay capable of quantifying intact and defective proviral HIV-1 DNA of subtype B and C.
Primer and probe sequences were strategically positioned at conserved regions in psi and env and adapted to subtype B&C. In silico analysis of 752 subtype B and 697 subtype C near-full length genome sequences (nFGS) was performed to predict the specificity and sensitivity. Gblocks were used to determine the limit of blank (LoB), limit of detection (LoD), and different annealing temperatures were tested to address impact of sequence variability.
The in silico analysis showed that the HIV-1 B&C IPDA correctly identified 100% of the intact subtype B, and 86% of the subtype C sequences. In contrast, the original IPDA identified 86% and 12% of these subtype B and C sequences as intact. Furthermore, the HIV-1 B&C IPDA correctly identified hypermutated (87% and 88%) and other defective sequences (73% and 66%) for subtype B and C with comparable specificity as the original IPDA for subtype B (59% and 63%). Subtype B cis-acting sequences were more frequently identified as intact by the HIV-1 B&C IPDA compared to the original IPDA (39% and 2%). The LoB for intact proviral DNA copies was 0, and the LoD for intact proviral DNA copies was 6 (> 95% certainty) at 60 °C. Quantification of 2-6 copies can be performed with > 80% certainty. Lowering the annealing temperature to 55 °C slightly lowered the specificity but prevented exclusion of samples with single mutations in the primer/probe region.
We developed a robust and sensitive assay for the quantification of intact and defective HIV-1 subtype B and C proviral DNA, making this a suitable tool to monitor the impact of (large-scale) curative interventions.
Summary
In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical ...density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites.
Introduction
To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters.
Methods
Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history.
Results
After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters.
Conclusions
In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.
To examine the association between cigarette smoking and age-related maculopathy (ARM) including age-related macular degeneration (AMD) in the European population.
Cross-sectional study.
Four ...thousand seven hundred fifty randomly sampled > or =65-year-olds from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain).
Participants underwent an eye examination and digital retinal photography. The images were graded at a single center. Smoking history was ascertained by a structured questionnaire administered by trained fieldworkers. Multinomial and binary logistic regressions were used to examine the association between smoking history and ARM grade and type of AMD, taking account of potential confounders and the multicenter study design.
Photographic images were graded according to the International Classification System for ARM and stratified using the Rotterdam staging system into 5 exclusive stages (ARM 0-3 and ARM 4, also known as AMD). Age-related macular degeneration also was classified as neovascular AMD or geographic atrophy (GA).
One hundred fifty-eight cases were categorized as AMD (109 neovascular AMD and 49 GA); 2260 had no signs of ARM (ARM 0). Current smokers had increased odds of neovascular AMD (odds ratio OR, 2.6; 95% confidence interval CI, 1.4-4.8) or GA (OR, 4.8; 95% CI, 2.1-11.1), whereas for ex-smokers the odds were around 1.7. Compared with people with unilateral AMD, those with bilateral AMD were more likely to have a history of heavy smoking in the previous 25 years (OR, 5.1; 95% CI, 1.3-20.0). The attributable fraction for AMD due to smoking was 27% (95% CI, 19%-33%). There was no consistent association with ARM grades 1 to 3 and smoking.
These findings highlight the need for increasing public awareness of the risks associated with smoking and the benefit of quitting smoking. Patients with unilateral disease who are current smokers should be advised of the risk of second-eye disease.
We have estimated photometric redshifts (z
phot) for more than 1.1 million galaxies of the public European Southern Observatory (ESO) Kilo-Degree Survey (KiDS) data release 2. KiDS is an optical ...wide-field imaging survey carried out with the Very Large Telescope (VLT) Survey Telescope (VST) and the OmegaCAM camera, which aims to tackle open questions in cosmology and galaxy evolution, such as the origin of dark energy and the channel of galaxy mass growth. We present a catalogue of photometric redshifts obtained using the Multi-Layer Perceptron with Quasi-Newton Algorithm (MLPQNA) model, provided within the framework of the DAta Mining and Exploration Web Application REsource (DAMEWARE). These photometric redshifts are based on a spectroscopic knowledge base that was obtained by merging spectroscopic data sets from the Galaxy and Mass Assembly (GAMA) data release 2 and the Sloan Digital Sky Survey III (SDSS-III) data release 9. The overall 1σ uncertainty on Δz = (z
spec − z
phot)/(1 + z
spec) is ∼0.03, with a very small average bias of ∼0.001, a normalized median absolute deviation of ∼0.02 and a fraction of catastrophic outliers (|Δz| > 0.15) of ∼0.4 per cent.
Purpose
Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver ...metastases (NELM) treated with holmium-166-microspheres radioembolization (
166
Ho-radioembolization).
Materials and methods
Single center, retrospective study included patients with NELM that received
166
Ho-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (D
t
) and whole liver healthy tissue (D
h
) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS).
Results
Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 – 82 months). Mean D
t
in non-responders was 68 Gy versus 118 Gy in responders,
p
= 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a D
t
of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1–2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI 10.2;19.8) and median OS was not reached.
Conclusion
This study confirms the safety and efficacy of
166
Ho-radioembolization in NELM in a real-world setting. A clear dose–response relationship was demonstrated and future studies should aim at a D
t
of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.
The physics of radioembolization Bastiaannet, Remco; Kappadath, S. Cheenu; Kunnen, Britt ...
EJNMMI physics,
11/2018, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable ...toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients.
In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics’ perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry.
This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible.
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