Evaluation of PSA and PSA Density in a Multiparametric Magnetic Resonance Imaging-Directed Diagnostic Pathway for Suspected Prostate Cancer: The INNOVATE Trial

OBJECTIVES: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. METHODS: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging–Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. RESULTS: 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged <50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. CONCLUSIONS: The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing

Bad news from Fallujah

This study uses the thematic analysis developed by the Glasgow University Media Group to explore how the US, UK and German national press covered the US/Coalition assault on the Iraqi city of Fallujah in November 2004. The study relies on quantitative and qualitative full text content analyses to assess 428 news, editorial and commentary items. The article suggests that, while government and military officials of the US/Coalition had argued the military ‘operation’ was necessary to secure Iraq and defeat an ‘insurgency’, organisations and actors from Iraqi society refer to the ‘operation’ as ‘collective punishment’ and a ‘massacre’ that targeted the Iraqi population. The article investigates how the press represented each of these perspectives. The findings suggest that the press overemphasised the US/Coalition perspective despite striking counter evidence. Critical aspects of coverage largely focused on tactical elements of the military dimension of the event. The article concludes that such findings are in accord with hegemonic models of media performance

Search for anomalous production of di-lepton events with missing transverse momentum in e(+)e(-) collisions at root s = 161 and 172 GeV

Events containing a pair of charged leptons and significant missing transverse momentum are selected from a data sample corresponding to a total integrated luminosity of 20.6 pb^-1 at centre-of-mass energies of 161 GeV and 172 GeV. The observed number of events, four at 161 GeV and nine at 172 GeV, is consistent with the number expected from Standard Model processes, predominantly arising from W+W- production with each W decaying leptonically. This topology is also an experimental signature for the pair production of new particles that decay to a charged lepton accompanied by one or more invisible particles. Further event selection criteria are described that optimise the sensitivity to particular new physics channels. No evidence for new phenomena is observed and limits on the production of scalar charged lepton pairs and other new particles are presented

Tests of the standard model and constraints on new physics from measurements of fermion-pair production at 130-172GeV at LEP

Production of events with hadronic and leptonic final states has been measured in e(+)e(-) collisions at centre-of-mass energies of 130-172 GeV, using the OPAL detector at LEP. Cross-sections and leptonic forward-backward asymmetries are presented, both including and excluding the dominant production of radiative Z gamma events, and compared to Standard Model expectations. The ratio R-b of the cross-section for production to the hadronic cross-section has been measured. In a model-independent fit to the Z lineshape, the data have been used to obtain an improved precision on the measurement of gamma-Z interference. The energy dependence of alpha(em) has been investigated. The measurements have also been used to obtain limits on extensions of the Standard Model described by effective four-fermion contact interactions, to search for t-channel contributions from new massive particles and to place limits on gaugino pair production with subsequent decay of the gaugino into a light gluino and a quark pair

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

Search for chargino and neutralino production at √s=170 and 172 GeV at LEP

A search for charginos and neutralinos, predicted by supersymmetric theories, has been performed using a data sample of 10.310.3 pb −1−1 at centre-of-mass energies of s√=s= 170 and 172 GeV with the OPAL detector at LEP. No evidence for these particles has been found. The results are combined with those from previous OPAL chargino and neutralino searches at lower energies to obtain limits. Exclusion regions at 95% C.L. of parameters of the Minimal Supersymmetric Standard Model are determined. Within this framework, for tanβ≥1.0tan⁡β≥1.0 , lower mass limits are placed on the lightest chargino and the three lightest neutralinos. The 95% C.L. lower mass limit on the lightest chargino, assuming that it is heavier than the lightest neutralino by more than 10 GeV, is 84.5 GeV for the case of a large universal scalar mass ( m0>m0> 1 TeV) and 65.7 GeV for the smallest m0m0 compatible with current limits on the sneutrino mass and slepton cross-sections. The lower limit on the lightest neutralino mass at 95% C.L. for tanβ≥1.0tan⁡β≥1.0 is 24.7 GeV for m0=1m0=1 TeV and 13.3 GeV for the minimum m0m0 scenario. These mass limits are higher for increasing values of tanβtan⁡β . The interpretation of the limits in terms of gluino and scalar quark mass limits is also given