: Prebiopsy multiparametric magnetic resonance imaging (mpMRI) is increasingly used in prostate cancer diagnosis. The reported negative predictive value (NPV) of mpMRI is used by some clinicians to ...aid in decision making about whether or not to proceed to biopsy.
: We aim to perform a contemporary systematic review that reflects the latest literature on optimal mpMRI techniques and scoring systems to update the NPV of mpMRI for clinically significant prostate cancer (csPCa).
: We conducted a systematic literature search and included studies from 2016 to September 4, 2019, which assessed the NPV of mpMRI for csPCa, using biopsy or clinical follow-up as the reference standard. To ensure that studies included in this analysis reflect contemporary practice, we only included studies in which mpMRI findings were interpreted according to the Prostate Imaging Reporting and Data System (PIRADS) or similar Likert grading system. We define negative mpMRI as either (1) PIRADS/Likert 1–2 or (2) PIRADS/Likert 1–3; csPCa was defined as either (1) Gleason grade group ≥2 or (2) Gleason grade group ≥3. We calculated NPV separately for each combination of negative mpMRI and csPCa.
: A total of 42 studies with 7321 patients met our inclusion criteria and were included for analysis. Using definition (1) for negative mpMRI and csPCa, the pooled NPV for biopsy-naïve men was 90.8% (95% confidence interval CI 88.1–93.1%). When defining csPCa using definition (2), the NPV for csPCa was 97.1% (95% CI 94.9–98.7%). Calculation of the pooled NPV using definition (2) for negative mpMRI and definition (1) for csPCa yielded the following: 86.8% (95% CI 80.1–92.4%). Using definition (2) for both negative mpMRI and csPCa, the pooled NPV from two studies was 96.1% (95% CI 93.4–98.2%).
: Multiparametric MRI of the prostate is generally an accurate test for ruling out csPCa. However, we observed heterogeneity in the NPV estimates, and local institutional data should form the basis of decision making if available.
: The negative predictive values should assist in decision making for clinicians considering not proceeding to biopsy in men with elevated age-specific prostate-specific antigen and multiparametric magnetic resonance imaging reported as negative (or equivocal) on Prostate Imaging Reporting and Data System/Likert scoring. Some 7–10% of men, depending on the setting, will miss a diagnosis of clinically significant cancer if they do not proceed to biopsy. Given the institutional variation in results, it is of upmost importance to base decision making on local data if available.
Depending on definition of “negative multiparametric magnetic resonance imaging” and “clinically significant prostate cancer”, the negative predictive value ranged from 84% to 97%, suggesting that it is a reliable test to rule out clinically significant prostate cancer.
We present the set of deep Neutron Star Interior Composition Explorer (NICER) X-ray timing observations of the nearby rotation-powered millisecond pulsars PSRs J0437−4715, J0030+0451, J1231−1411, and ...J2124−3358, selected as targets for constraining the mass-radius relation of neutron stars and the dense matter equation of state (EoS) via modeling of their pulsed thermal X-ray emission. We describe the instrument, observations, and data processing/reduction procedures, as well as the series of investigations conducted to ensure that the properties of the data sets are suitable for parameter estimation analyses to produce reliable constraints on the neutron star mass-radius relation and the dense matter EoS. We find that the long-term timing and flux behavior and the Fourier-domain properties of the event data do not exhibit any anomalies that could adversely affect the intended measurements. From phase-selected spectroscopy, we find that emission from the individual pulse peaks is well described by a single-temperature hydrogen atmosphere spectrum, with the exception of PSR J0437−4715, for which multiple temperatures are required.
Summary Background The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy ...for locally advanced prostate cancer. Here we report the 10-year results. Methods Between June, 1996, and February, 2000, 818 men with T2b, T2c, T3, and T4 N0 M0 prostate cancers were randomly assigned to receive radiotherapy alone, 3 months of NADT plus radiotherapy, or 6 months of NADT plus radiotherapy. The radiotherapy dose for all groups was 66 Gy, delivered to the prostate and seminal vesicles (excluding pelvic nodes) in 33 fractions of 2 Gy per day (excluding weekends) over 6·5–7·0 weeks. NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day. NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group. Primary endpoints were prostate-cancer-specific mortality and all-cause mortality. Treatment allocation was open label and randomisation was done with a minimisation technique according to age, clinical stage, tumour grade, and initial prostate-specific antigen concentration (PSA). Analysis was by intention-to-treat. The trial has been closed to follow-up and all main endpoint analyses are completed. The trial is registered with the Australian New Zealand Clinical Trials Registry , number ACTRN12607000237482. Findings 802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10·6 years (IQR 6·9–11·6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0·72, 95% CI 0·57–0·90; p=0·003) and local progression (0·49, 0·33–0·73; p=0·0005), and improved event-free survival (0·63, 0·52–0·77; p<0·0001). 6 months of NADT further reduced PSA progression (0·57, 0·46–0·72; p<0·0001) and local progression (0·45, 0·30–0·66; p=0·0001), and led to a greater improvement in event-free survival (0·51, 0·42–0·61, p<0·0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0·89, 0·60–1·31; p=0·550), prostate cancer-specific mortality (0·86, 0·60–1·23; p=0·398), or all-cause mortality (0·84, 0·65–1·08; p=0·180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0·49, 0·31–0·76; p=0·001), prostate cancer-specific mortality (0·49, 0·32–0·74; p=0·0008), and all-cause mortality (0·63, 0·48–0·83; p=0·0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation. Interpretation 6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation. Funding Australian Government National Health and Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough.
Postural control research has focused on standing balance experiments on platforms moving with relatively large amplitudes (0.1-0.2 m). This study investigated balance strategies while standing on a ...platform moving 4 mm in anterior-posterior direction with frequency scaled linearly from 0.4 to 6 Hz. Platform motion and kinematic and kinetic information for nine healthy participants were recorded using motion capture and force plate systems. Coordination between hip, knee and ankle joint torque, and centre of mass (COM) and centre of pressure (COP) motion was quantified by vector coding. Significant main effect of platform frequency for knee-ankle and COP-COM phase relationship was observed (p = 0.023, p = 0.016). At frequencies below 2.11 and 2.34 Hz, ankle strategy was recruited. With ankle strategy, in-phase COP-COM motion with COP dominancy occurred at frequencies below 2.19 and 2.23 Hz during scaling up and down, respectively. As platform frequency passed these values, COM dominated over COP which was followed by anti-phase knee-ankle torque, called a knee strategy, and anti-phase motion between the COP and COM that allowed COP to regain dominance over COM. Collectively, we reveal knee strategy as a new and relevant strategy in real-life settings, and transition between ankle and knee strategies that underpinned transition between COP-COM relative motion.
By modification of pore size and morphology, pore‐expanded variants of SBA‐15 and KIT‐6 have been utilised as mesoporous silica supports for the immobilisation of a bimetallic aluminium‐salen ...complex. The performance of the resulting heterogeneous catalysts in the synthesis of cyclic carbonates from carbon dioxide and terminal epoxides was assessed. Support materials which retained higher pore volume and surface areas after catalyst immobilisation demonstrated enhanced conversions to the desired cyclic carbonates. This was rationalised to be a consequence of the promotion of reactant mass transport through a less‐inhibited pore structure.
We evaluated whether the timing of fatal myocardial infarction (MI) was influenced by the administration of androgen suppression therapy (AST).
The study cohort comprised 1,372 men who were enrolled ...onto three randomized trials between February 1995 and June 2001. In the three trials, the men were randomly assigned to receive radiation therapy with 0 versus 3 versus 6, 3 versus 8, or 0 versus 6 months of AST. Fine and Gray's regression was used to determine the clinical factors associated with the time to fatal MI, and estimates of time to fatal MI were calculated using a cumulative incidence method. When comparing the cumulative incidence estimates using Gray's k-sample P values, increased weight was ascribed to the earlier data because recovery of testosterone is expected for most men within 2 years after short-course AST.
Men age 65 years or older who received 6 months of AST experienced shorter times to fatal MIs compared with men in this age group who did not receive AST (P = .017) and men younger than 65 years (P = .016). No significant difference (P = .97) was observed in the time to fatal MIs in men age 65 years or older who received 6 to 8 months of AST compared with 3 months of AST.
The use of AST is associated with earlier onset of fatal MIs in men age 65 years or older who are treated for 6 months compared with men who are not treated with AST.
Abstract
The hot gas that constitutes the intracluster medium (ICM) has been studied at X-ray and millimeter/submillimeter wavelengths (Sunyaev–Zel’dovich effect) for decades. Fast radio bursts ...(FRBs) offer an additional method of directly measuring the ICM and gas surrounding clusters via observables such as dispersion measure (DM) and Faraday rotation measure. We report the discovery of two FRB sources detected with the Deep Synoptic Array whose host galaxies belong to massive galaxy clusters. In both cases, the FRBs exhibit excess extragalactic DM, some of which likely originate in the ICM of their respective clusters. FRB 20220914A resides in the galaxy cluster A2310 at
z
= 0.1125 with a projected offset from the cluster center of 520 ± 50 kpc. The host of a second source, FRB 20220509G, is an elliptical galaxy at
z
= 0.0894 that belongs to the galaxy cluster A2311 at the projected offset of 870 ± 50 kpc. These sources represent the first time an FRB has been localized to a galaxy cluster. We combine our FRB data with archival X-ray, Sunyaev–Zel'dovich (SZ), and optical observations of these clusters in order to infer properties of the ICM, including a measurement of gas temperature from DM and
y
SZ
of 0.8–3.9 keV. We then compare our results to massive cluster halos from the IllustrisTNG simulation. Finally, we describe how large samples of localized FRBs from future surveys will constrain the ICM, particularly beyond the virial radius of clusters.
Abstract
We report the detection and interferometric localization of the repeating fast radio burst (FRB) source FRB 20220912A during commissioning observations with the Deep Synoptic Array ...(DSA-110). Two bursts were detected from FRB 20220912A, one each on 2022 October 18 and 2022 October 25. The best-fit position is (R.A. J2000, decl. J2000) = (23:09:04.9, +48:42:25.4), with a 90% confidence error ellipse with radii ±2″ and ±1″ in R.A. and decl., respectively. The two bursts are polarized, and we find a Faraday rotation measure that is consistent with the low value of +0.6 rad m
−2
reported by CHIME/FRB. The DSA-110 localization overlaps with the galaxy PSO J347.2702+48.7066 at a redshift
z
= 0.0771, which we identify as the likely host. PSO J347.2702+48.7066 has a stellar mass of approximately 10
10
M
⊙
, modest internal dust extinction, and a star formation rate likely in excess of 0.1
M
⊙
yr
−1
. The host-galaxy contribution to the dispersion measure is likely ≲50 pc cm
−3
. The FRB 20220912A source is therefore likely viewed along a tenuous plasma column through the host galaxy.
Abstract We report on a full-polarization analysis of the first 25 as yet nonrepeating fast radio bursts (FRBs) detected at 1.4 GHz by the 110-antenna Deep Synoptic Array (DSA-110) during ...commissioning observations. We present details of the data-reduction, calibration, and analysis procedures developed for this novel instrument. Faraday rotation measures (RMs) are searched between ±10 6 rad m −2 and detected for 20 FRBs, with magnitudes ranging from 4 to 4670 rad m −2 . Fifteen out of 25 FRBs are consistent with 100% polarization, 10 of which have high (≥70%) linear-polarization fractions and two of which have high (≥30%) circular-polarization fractions. Our results disfavor multipath RM scattering as a dominant depolarization mechanism. Polarization-state and possible RM variations are observed in the four FRBs with multiple subcomponents. We combine the DSA-110 sample with polarimetry of previously published FRBs, and compare the polarization properties of FRB subpopulations and FRBs with Galactic pulsars. Although FRB polarization fractions are typically higher than those of Galactic pulsars, and cover a wider range than those of pulsar single pulses, they resemble those of the youngest (characteristic ages <10 5 yr) pulsars. Our results support a scenario wherein FRB emission is intrinsically highly linearly polarized, and propagation effects can result in conversion to circular polarization and depolarization. Young pulsar emission and magnetospheric propagation geometries may form a useful analogy for the origin of FRB polarization.
Summary Background We investigated whether 18 months of androgen suppression plus radiotherapy, with or without 18 months of zoledronic acid, is more effective than 6 months of neoadjuvant androgen ...suppression plus radiotherapy with or without zoledronic acid. Methods We did an open-label, randomised, 2 × 2 factorial trial in men with locally advanced prostate cancer (either T2a N0 M0 prostatic adenocarcinomas with prostate-specific antigen PSA ≥10 μg/L and a Gleason score of ≥7, or T2b–4 N0 M0 tumours regardless of PSA and Gleason score). We randomly allocated patients by computer-generated minimisation—stratified by centre, baseline PSA, tumour stage, Gleason score, and use of a brachytherapy boost—to one of four groups in a 1:1:1:1 ratio. Patients in the control group were treated with neoadjuvant androgen suppression with leuprorelin (22·5 mg every 3 months, intramuscularly) for 6 months (short-term) and radiotherapy alone (designated STAS); this procedure was either followed by another 12 months of androgen suppression with leuprorelin (intermediate-term; ITAS) or accompanied by 18 months of zoledronic acid (4 mg every 3 months for 18 months, intravenously; STAS plus zoledronic acid) or by both (ITAS plus zoledronic acid). The primary endpoint was prostate cancer-specific mortality. This analysis represents the first, preplanned assessment of oncological endpoints, 5 years after treatment. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov , number NCT00193856. Findings Between Oct 20, 2003, and Aug 15, 2007, 1071 men were randomly assigned to STAS (n=268), STAS plus zoledronic acid (n=268), ITAS (n=268), and ITAS plus zoledronic acid (n=267). Median follow-up was 7·4 years (IQR 6·5–8·4). Cumulative incidences of prostate cancer-specific mortality were 4·1% (95% CI 2·2–7·0) in the STAS group, 7·8% (4·9–11·5) in the STAS plus zoledronic acid group, 7·4% (4·6–11·0) in the ITAS group, and 4·3% (2·3–7·3) in the ITAS plus zoledronic acid group. Cumulative incidence of all-cause mortality was 17·0% (13·0–22·1), 18·9% (14·6–24·2), 19·4% (15·0–24·7), and 13·9% (10·3–18·8), respectively. Neither prostate cancer-specific mortality nor all-cause mortality differed between control and experimental groups. Cumulative incidence of PSA progression was 34·2% (28·6–39·9) in the STAS group, 39·6% (33·6–45·5) in the STAS plus zoledronic acid group, 29·2% (23·8–34·8) in the ITAS group, and 26·0% (20·8–31·4) in the ITAS plus zoledronic acid group. Compared with STAS, no difference was noted in PSA progression with ITAS or STAS plus zoledronic acid; however, ITAS plus zoledronic acid reduced PSA progression (sub-hazard ratio SHR 0·71, 95% CI 0·53–0·95; p=0·021). Cumulative incidence of local progression was 4·1% (2·2–7·0) in the STAS group, 6·1% (3·7–9·5) in the STAS plus zoledronic acid group, 1·5% (0·5–3·7) in the ITAS group, and 3·4% (1·7–6·1) in the ITAS plus zoledronic acid group; no differences were noted between groups. Cumulative incidences of bone progression were 7·5% (4·8–11·1), 14·6% (10·6–19·2), 8·4% (5·5–12·2), and 7·6% (4·8–11·2), respectively. Compared with STAS, STAS plus zoledronic acid increased the risk of bone progression (SHR 1·90, 95% CI 1·14–3·17; p=0·012), but no differences were noted with the other two groups. Cumulative incidence of distant progression was 14·7% (10·7–19·2) in the STAS group, 17·3% (13·0–22·1) in the STAS plus zoledronic acid group, 14·2% (10·3–18·7) in the ITAS group, and 11·1% (7·6–15·2) in the ITAS plus zoledronic acid group; no differences were recorded between groups. Cumulative incidence of secondary therapeutic intervention was 25·6% (20·5–30·9), 28·9% (23·5–34·5), 20·7% (16·1–25·9), and 15·3% (11·3–20·0), respectively. Compared with STAS, ITAS plus zoledronic acid reduced the need for secondary therapeutic intervention (SHR 0·67, 95% CI 0·48–0·95; p=0·024); no differences were noted with the other two groups. An interaction between trial factors was recorded for Gleason score; therefore, we did pairwise comparisons between all groups. Post-hoc analyses suggested that the reductions in PSA progression and decreased need for secondary therapeutic intervention with ITAS plus zoledronic acid were restricted to tumours with a Gleason score of 8–10, and that ITAS was better than STAS in tumours with a Gleason score of 7 or lower. Long-term morbidity and quality-of-life scores were not affected adversely by 18 months of androgen suppression or zoledronic acid. Interpretation Compared with STAS, ITAS plus zoledronic acid was more effective for treatment of prostate cancers with a Gleason score of 8–10, and ITAS alone was effective for tumours with a Gleason score of 7 or lower. Nevertheless, these findings are based on secondary endpoint data and post-hoc analyses and must be regarded cautiously. Long- term follow-up is necessary, as is external validation of the interaction between zoledronic acid and Gleason score. STAS plus zoledronic acid can be ruled out as a potential therapeutic option. Funding National Health and Medical Research Council of Australia, Novartis Pharmaceuticals Australia, Abbott Pharmaceuticals Australia, New Zealand Health Research Council, New Zealand Cancer Society, University of Newcastle (Australia), Calvary Health Care (Calvary Mater Newcastle Radiation Oncology Fund), Hunter Medical Research Institute, Maitland Cancer Appeal, Cancer Standards Institute New Zealand.
PDF
