Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

Contains fulltext : 69173.pdf (publisher's version ) (Closed access)OBJECTIVES: Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate cancer. METHODS: RP specimens of 542 patients were evaluated with a median follow-up of 39.5 months (range 0.6-150 months). MTD was defined as the largest diameter of the largest tumor; high-risk as >or=T2c or PSA level>20 ng/ml or Gleason score>or=8 and BCR as two consecutive PSA levels>0.10 ng/ml. Proportional hazards multivariable regression models were composed to determine prognostic factors for BCR. RESULTS: Overall, 114 patients developed BCR after RP. The overall 5-year risk of BCR was 25% (95% CI=20.4-29.6), and median MTD was 24 mm (range 1-65). MTD in the total and high-risk group was associated with total tumor volume, volume of the largest tumor, pre-operative PSA levels, and Gleason score. In a univariable analyses, MTD was weakly associated with risk of BCR (HR=1.02 per mm increase, 95% CI=1.002-1.035, P=0.024) in the total group; in the high-risk group this association was lost (HR=1.01, 95%CI=0.99-1.03, P=0.18). Multivariable analyses indicated that positive surgical margins, higher Gleason score, advanced pathological stage, and multiple tumors were the main prognostic factors for BCR irrespective of the risk profile. MTD did not provide additional information. CONCLUSIONS: MTD is not an independent prognostic factor for BCR in patients treated with RP, irrespective of the risk profile

A comparative study of dipolarization fronts at MMS and Cluster

We present a statistical study of dipolarization fronts (DFs), using magnetic field data from MMS and Cluster, at radial distances below 12 RE and 20 RE, respectively. Assuming that the DFs have a semicircular cross section and are propelled by the magnetic tension force, we used multispacecraft observations to determine the DF velocities. About three quarters of the DFs propagate earthward and about one quarter tailward. Generally, MMS is in a more dipolar magnetic field region and observes larger‐amplitude DFs than Cluster. The major findings obtained in this study are as follows: (1) At MMS ∼57 % of the DFs move faster than 150 km/s, while at Cluster only ∼35 %, indicating a variable flux transport rate inside the flow‐braking region. (2) Larger DF velocities correspond to higher Bz values directly ahead of the DFs. We interpret this as a snow plow‐like phenomenon, resulting from a higher magnetic flux pileup ahead of DFs with higher velocities.Key PointsMMS is generally located in a more dipolar magnetic field region and observes larger‐amplitude DFs than Cluster farther down the tailA larger fraction of DFs move faster closer to Earth, suggesting variable flux transport rates in the flow‐braking regionLarger DF velocities correspond to a higher Bz directly ahead of DFs, suggesting a higher flux pileup ahead of DFs with higher velocitiesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133541/1/grl54539_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133541/2/grl54539.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133541/3/grl54539-sup-0001-supplementary.pd

Suitability of PSA-detected localised prostate cancers for focal therapy: Experience from the ProtecT study

This article is available through a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. Copyright @ 2011 Cancer Research UK.Background: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Methods: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Results: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38–66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Conclusion: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.National Institute for Health Researc

Evidence for the generation of juvenile granitic crust during continental extension, Mineral Mountains Batholith, Utah

This is the published version. Copyright 1976 American Geophysical Union. All Rights Reserved.Field, chemical and isotopic data from the Miocene Mineral Mountains batholith in southwest Utah are consistent with the batholith being derived through differentiation of material recently separated from the lithospheric mantle, with little involvement of pre-Oligocene crust. The batholith ranges in composition and texture from diabase and gabbro to high-silica rhyolite and granite and is distinctly calcalkaline in nature. Field evidence for anatexis of intermediate-composition Oligocene crust and magma mixing suggest that fractional melting and mixing were important processes during the evolution of the batholith. Major oxide and rare earth element data for the batholith are consistent with chemical evolution of the magma system being controlled by fractionation of hornblende, plagioclase and sphene (all of which occur in restitic portions of Miocene migmatites exposed in the field area) during partial melting, and mixing between gabbro and granite. Isotopic data indicate a lithospheric mantle source for mafic rocks in the study area and, on the basis of field data and their similarity in isotopic composition, granitic rocks are interpreted to be derived indirectly from the same source during Basin and Range extension. Evolution of the granites is hypothesized to involve a series of partial melting steps, one of which is exposed in the batholith, which refine mantle-derived gabbros into high-silica rocks. Thus the Mineral Mountains batholith represents juvenile granitic material added to the crust during extension. This raises the possibility that extension may be an important granitic crust-forming event. Furthermore, this suggests that pure-shear igneous inflation of the crust by the mantle can be an important mechanism during extensional deformation. Data presented here indicate that fractional melting of young mafic crust may be an important process in the evolution of isotopically homogeneous intrusive suites which span a broad compositional range. Furthermore, the data support the idea that lithospheric mantle in the Great Basin region may be Proterozoic in age

Mixing of rhyolite, trachyte and basalt magma erupted from a vertically and laterally zoned reservoir, composite flow P1, Gran Canaria

The 14.1 Ma composite welded ignimbrite P1 (45 km3 DRE) on Gran Canaria is compositionally zoned from a felsic lower part to a basaltic top. It is composed of four component magmas mixed in vertically varying proportions: (1) Na-rhyolite (10 km3) zoned from crystal-poor to highly phyric; (2) a continuously zoned, evolved trachyte to sodic trachyandesite magma group (6 km3); (3) a minor fraction of Na-poor trachyandesite (<1 km3); and (4) nearly aphyric basalt (26 km3) zoned from 4.3 to 5.2 wt% MgO. We distinguish three sites and phases of mixing: (a) Mutual mineral inclusions show that mixing between trachytic and rhyolitic magmas occurred during early stages of their intratelluric crystallization, providing evidence for long-term residence in a common reservoir prior to eruption. This first phase of mixing was retarded by increasing viscosity of the rhyolite magma upon massive anorthoclase precipitation and accumulation. (b) All component magmas probably erupted through a ring-fissure from a common upper-crustal reservoir into which the basalt intruded during eruption. The second phase of mixing occurred during simultaneous withdrawal of magmas from the chamber and ascent through the conduit. The overall withdrawal and mixing pattern evolved in response to pre-eruptive chamber zonation and density and viscosity relationships among the magmas. Minor sectorial variations around the caldera reflect both varying configurations at the conduit entrance and unsteady discharge. (c) During each eruptive pulse, fragmentation and particulate transport in the vent and as pyroclastic flows caused additional mixing by reducing the length scale of heterogeneities. Based on considerations of magma density changes during crystallization, magma temperature constraints, and the pattern of withdrawal during eruption, we propose that eruption tapped the P1 magma chamber during a transient state of concentric zonation, which had resulted from destruction of a formerly layered zonation in order to maintain gravitational equilibrium. Our model of magma chamber zonation at the time of eruption envisages a basal high-density Na-poor trachyandesite layer that was overlain by a central mass of highly phyric rhyolite magma mantled by a sheath of vertically zoned trachyte-trachyandesite magma along the chamber walls. A conventional model of vertically stacked horizontal layers cannot account for the deduced density relationships nor for the withdrawal pattern

Hydrothermal alteration of andesitic lava domes can lead to explosive volcanic behaviour

Dome-forming volcanoes are among the most hazardous volcanoes on Earth. Magmatic outgassing can be hindered if the permeability of a lava dome is reduced, promoting pore pressure augmentation and explosive behaviour. Laboratory data show that acid-sulphate alteration, common to volcanoes worldwide, can reduce the permeability on the sample lengthscale by up to four orders of magnitude and is the result of pore- and microfracture-filling mineral precipitation. Calculations using these data demonstrate that intense alteration can reduce the equivalent permeability of a dome by two orders of magnitude, which we show using numerical modelling to be sufficient to increase pore pressure. The fragmentation criterion shows that the predicted pore pressure increase is capable of fragmenting the majority of dome-forming materials, thus promoting explosive volcanism. It is crucial that hydrothermal alteration, which develops over months to years, is monitored at dome-forming volcanoes and is incorporated into real-time hazard assessments

Unique Type I Interferon Responses Determine the Functional Fate of Migratory Lung Dendritic Cells during Influenza Virus Infection

Migratory lung dendritic cells (DCs) transport viral antigen from the lungs to the draining mediastinal lymph nodes (MLNs) during influenza virus infection to initiate the adaptive immune response. Two major migratory DC subsets, CD103+ DCs and CD11bhigh DCs participate in this function and it is not clear if these antigen presenting cell (APC) populations become directly infected and if so whether their activity is influenced by the infection. In these experiments we show that both subpopulations can become infected and migrate to the draining MLN but a difference in their response to type I interferon (I-IFN) signaling dictates the capacity of the virus to replicate. CD103+ DCs allow the virus to replicate to significantly higher levels than do the CD11bhigh DCs, and they release infectious virus in the MLNs and when cultured ex-vivo. Virus replication in CD11bhigh DCs is inhibited by I-IFNs, since ablation of the I-IFN receptor (IFNAR) signaling permits virus to replicate vigorously and productively in this subset. Interestingly, CD103+ DCs are less sensitive to I-IFNs upregulating interferon-induced genes to a lesser extent than CD11bhigh DCs. The attenuated IFNAR signaling by CD103+ DCs correlates with their described superior antigen presentation capacity for naïve CD8+ T cells when compared to CD11bhigh DCs. Indeed ablation of IFNAR signaling equalizes the competency of the antigen presenting function for the two subpopulations. Thus, antigen presentation by lung DCs is proportional to virus replication and this is tightly constrained by I-IFN. The “interferon-resistant” CD103+ DCs may have evolved to ensure the presentation of viral antigens to T cells in I-IFN rich environments. Conversely, this trait may be exploitable by viral pathogens as a mechanism for systemic dissemination

Severe Pandemic H1N1 2009 Infection Is Associated with Transient NK and T Deficiency and Aberrant CD8 Responses

BACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired