Global polarization of Λ hyperons has been measured to be of the order of a few tenths of a percent in Au+Au collisions at √SNN = 200 GeV, with no significant difference between Λ and Λ¯. These new ...results reveal the collision energy dependence of the global polarization together with the results previously observed √SNN = 7.7 – 62.4 GeV and indicate noticeable vorticity of the medium created in non-central heavy-ion collisions at the highest RHIC collision energy.
The Λ (Λ¯) hyperon polarization along the beam direction has been measured in Au+Au collisions at sNN=200 GeV, for the first time in heavy-ion collisions. The polarization dependence on the ...hyperons' emission angle relative to the elliptic flow plane exhibits a second harmonic sine modulation, indicating a quadrupole pattern of the vorticity component along the beam direction, expected due to elliptic flow. The polarization is found to increase in more peripheral collisions, and shows no strong transverse momentum (pT) dependence at pT greater than 1 GeV/c. The magnitude of the signal is about 5 times smaller than those predicted by hydrodynamic and multiphase transport models; the observed phase of the emission angle dependence is also opposite to these model predictions. In contrast, the kinematic vorticity calculations in the blast-wave model tuned to reproduce particle spectra, elliptic flow, and the azimuthal dependence of the Gaussian source radii measured with the Hanbury Brown–Twiss intensity interferometry technique reproduce well the modulation phase measured in the data and capture the centrality and transverse momentum dependence of the polarization signal.
Here, we report a systematic measurement of cumulants, Cn, for net-proton, proton, and antiproton multiplicity distributions, and correlation functions, κn, for proton and antiproton multiplicity ...distributions up to the fourth order in Au+Au collisions at √sNN = 7.7, 11.5, 14.5, 19.6, 27, 39, 54.4, 62.4, and 200 GeV. The Cn and κn are presented as a function of collision energy, centrality and kinematic acceptance in rapidity, y, and transverse momentum, pT. The data were taken during the first phase of the Beam Energy Scan (BES) program (2010–2017) at the BNL Relativistic Heavy Ion Collider (RHIC) facility. The measurements are carried out at midrapidity (|y| < 0.5) and transverse momentum 0.4 < pT < 2.0GeV/c, using the STAR detector at RHIC. We observe a nonmonotonic energy dependence (√sNN = 7.7–62.4 GeV) of the net-proton C4/C2 with the significance of 3.1σ for the 0–5% central Au+Au collisions. This is consistent with the expectations of critical fluctuations in a QCD-inspired model. Thermal and transport model calculations show a monotonic variation with √sNN. For the multiparticle correlation functions, we observe significant negative values for a two-particle correlation function, κ2, of protons and antiprotons, which are mainly due to the effects of baryon number conservation. Furthermore, it is found that the four-particle correlation function, κ4, of protons plays a role in determining the energy dependence of proton C4/C1 below 19.6 GeV, which cannot be understood by the effect of baryon number conservation.
Purpose
Readers need to be informed about potential pitfalls of
68
GaGa-PSMA-11 PET interpretation.
Methods
Here we report
68
GaGa-PSMA-11 PET findings discordant with the histopathology/composite ...reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer.
Results
Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy (
n
= 11); other false positive findings were noted for prostate bed post prostatectomy (T,
n
= 2), pelvic nodes (N,
n
= 2), or extra pelvic lesions (M,
n
= 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) (
n
= 5), pelvic nodes (
n
= 1), and extra pelvic lesions (
n
= 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake.
Conclusion
68
GaGa-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of
68
GaGa-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants.
Trial registration number
ClinicalTrials.gov
Identifiers: NCT02940262 and NCT03353740.
We present measurements of bulk properties of the matter produced in Au+Au collisions at $\sqrt{s}$$_ {NN}$= 7.7, 11.5, 19.6, 27, and 39 GeV using identified hadrons (π±, K±, p, and $\bar{p}$) from ...the STAR experiment in the Beam Energy Scan (BES) Program at the Relativistic Heavy Ion Collider (RHIC). Midrapidity (| y | < 0.1) results for multiplicity densities dN / dy, average transverse momenta $\langle$pT$\rangle$, and particle ratios are presented. The chemical and kinetic freeze-out dynamics at these energies are discussed and presented as a function of collision centrality and energy. These results constitute the systematic measurements of bulk properties of matter formed in heavy-ion collisions over a broad range of energy (or baryon chemical potential) at RHIC.
•Adults with electrical injuries demonstrated worse physical functioning at 24 months post-injury than those with fire/flame injuries.•Adults with electrical injuries were nearly half as likely to be ...employed at 24 months post-injury than those with fire/flame injuries.•Results suggest a need for examination of return to work, work accommodations and performance at work following electrical injuries.
Electrical injuries exhibit significant acute and long-term sequelae. Amputation and neurological deficits are common in electrical injury survivors. There is a paucity of information on the long-term outcomes of this population. Therefore, this study examines the long-term outcomes of electrical injuries by comparing them to fire/flame injuries.
Data from the Burn Model System National Database collected between 1996 and 2015 was examined. Demographic and clinical characteristics for adult burn survivors with electrical and fire/flame injuries were compared. Satisfaction With Life Scale (SWLS), Short Form-12 Physical Composite Score (SF-12 PCS), Short Form-12 Mental Composite Score (SF-12 MCS), and employment status were examined at 24 months post-injury. Linear and logistic regression models were used to assess differences in outcome measures between groups, controlling for demographic and clinical variables.
A total of 1147 adult burn survivors (111 with electrical injuries; 1036 with fire/flame injuries) were included in this study. Persons with electrical injuries were more likely to be male and injured at work (p<0.001). SF-12 PCS scores were significantly worse for survivors with electrical injuries at 24 months post-injury than survivors with fire/flame injuries (p<0.01). Those with electrical injuries were nearly half as likely to be employed at 24 months post-injury than those with fire/flame injuries (p=0.002). There were no significant differences in SWLS and SF-12 MCS between groups.
Adult survivors with electrical injuries reported worse physical health and were less likely to be employed at 24 months post-injury compared to survivors with fire/flame injuries. A more detailed understanding of return to work barriers and work accommodations is merited for the electrical injury population. Furthermore, the results of this study should inform future resource allocation for the physical health and employment needs of this population.
Agents targeting prostate-specific membrane antigen (PSMA) comprise a rapidly emerging class of radiopharmaceuticals for diagnostic imaging of prostate cancer. Unlike most other PSMA agents with a ...urea backbone, CTT1057 is based on a phosphoramidate scaffold that irreversibly binds to PSMA. We conducted a first-in-humans phase I study of CTT1057 in patients with localized and metastatic prostate cancer. Methods: Two patient cohorts were recruited. Cohort A patients had biopsy-proven localized prostate cancer preceding radical prostatectomy, and cohort B patients had metastatic castration-resistant prostate cancer. Cohort A patients were imaged at multiple time points after intravenous injection with 362 ± 8 MBq of CTT1057 to evaluate the kinetics of CTT1057 and estimate radiation dose profiles. Mean organ-absorbed doses and effective doses were calculated. CTT1057 uptake in the prostate gland and regional lymph nodes was correlated with pathology, PSMA staining, and the results of conventional imaging. In cohort B, patients were imaged 60–120 min after injection of CTT1057. PET images were assessed for overall image quality, and areas of abnormal uptake were contrasted with conventional imaging. Results: In cohort A (n = 5), the average total effective dose was 0.023 mSv/MBq. The kidneys exhibited the highest absorbed dose, 0.067 mGy/MBq. The absorbed dose of the salivary glands was 0.015 mGy/MBq. For cohort B (n = 15), CTT1057 PET detected 97 metastatic lesions, and 44 of 56 bone metastases detected on CTT1057 PET (78.5%) were also detectable on bone scanning. Eight of 32 lymph nodes positive on CTT1057 PET (25%) were enlarged by size criteria on CT. Conclusion: CTT1057 is a promising novel phosphoramidate PSMA-targeting 18F-labeled PET radiopharmaceutical that demonstrates similar biodistribution to urea-based PSMA-targeted agents, with lower exposure to the kidneys and salivary glands. Metastatic lesions are detected with higher sensitivity on CTT1057 imaging than on conventional imaging. Further prospective studies with CTT1057 are warranted to elucidate its role in cancer imaging.
Intermediate-risk prostate cancer is a heterogeneous disease state with diverse treatment options. The 22-gene Decipher genomic classifier (GC) retrospectively has shown to improve risk ...stratification in these patients. We assessed the performance of the GC in men with intermediate-risk disease enrolled in NRG Oncology/RTOG 01-26 with updated follow-up.
After National Cancer Institute approval, biopsy slides were collected from NRG Oncology/RTOG 01-26, a randomized phase 3 trial of men with intermediate-risk prostate cancer randomized to 70.2 Gy versus 79.2 Gy of radiation therapy without androgen deprivation therapy. RNA was extracted from the highest-grade tumor foci to generate the locked 22-gene GC model. The primary endpoint for this ancillary project was disease progression (composite of biochemical failure, local failure, distant metastasis, prostate cancer-specific mortality, and use of salvage therapy). Individual endpoints were also assessed. Fine-Gray or cause-specific Cox multivariable models were constructed adjusting for randomization arm and trial stratification factors.
Two-hundred fifteen patient samples passed quality control for analysis. The median follow-up was 12.8 years (range, 2.4-17.7). On multivariable analysis, the 22-gene GC (per 0.1 unit) was independently prognostic for disease progression (subdistribution hazard ratio sHR, 1.12; 95% confidence interval CI, 1.00-1.26; P = .04), biochemical failure (sHR, 1.22; 95% CI, 1.10-1.37; P < .001), distant metastasis (sHR, 1.28; 95% CI, 1.06-1.55; P = .01), and prostate cancer-specific mortality (sHR, 1.45; 95% CI, 1.20-1.76; P < .001). Ten-year distant metastasis in GC low-risk patients was 4% compared with 16% for GC high-risk patients. In patients with lower GC scores, the 10-year difference in metastasis-free survival rate between arms was -7%, compared with 21% for higher GC patients (P-interaction = .04).
This study represents the first validation of a biopsy-based gene expression classifier, assessing both its prognostic and predictive value, using data from a randomized phase 3 trial of intermediate-risk prostate cancer. Decipher improves risk stratification and can aid in treatment decision-making in men with intermediate-risk disease.
The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there ...is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives.
The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents.
CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field.
These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes.
PURPOSETo determine if benign glandular tissue at the surgical margin (BGM) is associated with detectable prostate specific antigen (PSA) and/or biochemical recurrence (BCR) after radical ...prostatectomy (RP). MATERIALS AND METHODSParticipants underwent RP for localized prostate cancer between 2004 and 2018. Regression analysis was used to identify demographic, clinical and surgical factors associated with the likelihood of BGM presence on surgical pathology. Oncologic outcomes included detectable PSA (>0.03 ng/ml), BCR (≥0.2 ng/ml) and progression to BCR or salvage treatment after detectable PSA. Life tables and Cox proportional hazards regression models were used to determine the association of BGM and risk of oncologic outcomes. RESULTSA total of 1,082 men underwent RP for localized prostate cancer with BGM reported on surgical pathology and an undetectable postoperative PSA. BGM was present on 249 (23%) specimens. Younger age, bilateral nerve sparing surgery and robotic approach were associated with presence of BGM while malignancy at the surgical margin (MSM) was not. At 7 years after RP, 29% experienced detectable PSA and 11% had BCR. In the subgroup of men who reached detectable PSA, 79% had progression within 7 years. On multivariate Cox proportional hazards regression, BGM status was not independently associated with detectable PSA, BCR and/or progression from detectable PSA to BCR or salvage treatment. CONCLUSIONSThe presence of BGM at RP was not associated with increased risk of MSM, detectable PSA, BCR or progression after detectable PSA.
PDF
