Normalization of prostate specific antigen in patients treated with intensity modulated radiotherapy for clinically localized prostate cancer

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to determine the expected time to prostate specific antigen (PSA) normalization with or without neoadjuvant androgen deprivation (NAAD) therapy after treatment with intensity modulated radiotherapy (IMRT) for patients with clinically localized prostate cancer.</p> <p>Methods</p> <p>A retrospective cohort research design was used. A total of 133 patients with clinical stage T1c to T3b prostate cancer (2002 AJCC staging) treated in a community setting between January 2002 and July 2005 were reviewed for time to PSA normalization using 1 ng/mL and 2 ng/mL as criteria. All patients received IMRT as part of their management. Times to PSA normalization were calculated using the Kaplan-Meier method. Significance was assessed at p < 0.05.</p> <p>Results</p> <p>Fifty-six of the 133 patients received NAAD (42.1%). Thirty-one patients (23.8%) received radiation to a limited pelvic field followed by an IMRT boost, while 99 patients received IMRT alone (76.2%). The times to serum PSA normalization < 2 ng/mL when treated with or without NAAD were 298 ± 24 and 302 ± 33 days (mean ± SEM), respectively (p > 0.05), and 303 ± 24 and 405 ± 46 days, respectively, for PSA < 1 ng/mL (p < 0.05). Stage T1 and T2 tumors had significantly increased time to PSA normalization < 1 ng/mL in comparison to Stage T3 tumors. Also, higher Gleason scores were significantly correlated with a faster time to PSA normalization < 1 ng/mL.</p> <p>Conclusions</p> <p>Use of NAAD in conjunction with IMRT leads to a significantly shortened time to normalization of serum PSA < 1 ng/mL in patients with clinically localized prostate cancer.</p

Strontium Isotope Zoning in Garnet: Implications for Metamorphic Matrix Equilibration, Geochronology and Phase Equilibrium Modelling

In principle, garnet growth rates may be calculated from 87Rb/86Sr and 87Sr/86Sr measurements in garnet subsamples and the surrounding rock matrix. Because of low Rb/Sr, garnet should passively record the matrix decay of 87Rb to 87Sr as a progressive increase in 87Sr/86Sr from core to rim. This concept was tested by collecting Rb-Sr data for five garnet grains from four major orogenic belts: eastern Vermont (c. 380 Ma), western New Hampshire (c. 320 Ma), southern Chile (c. 75 Ma) and northwestern Italy (c. 35 Ma). Both normal Sr isotope zoning (increasing 87Sr/86Sr from core to rim) and inverse Sr zoning (decreasing 87Sr/86Sr from core to rim) were observed. Garnet and matrix isotope data commonly yielded grossly inaccurate model ages. Incomplete Rb and Sr equilibration among matrix minerals is invoked to explain the deviations between theoretical v. measured zoning patterns and the age disparities. Initially, the reactive matrix is dominated by rapidly equilibrating Rb-rich mica, which imparts high 87Sr/86Sr values in garnet cores. Progressive participation of slower equilibrating Sr-rich plagioclase buffers or even reduces 87Sr/86Sr, possibly leading to flat or decreasing 87Sr/86Sr from garnet cores to rims. Unusually high 87Sr/86Sr in garnet in combination with bulk matrix compositions causes erroneously young apparent ages, so metamorphic ages, growth rates, and associated heating and loading rates are likely suspect. Although Rb-Sr may be the most susceptible because of the profound disparities between mica and feldspar, zircon reactivity might influence the Lu-Hf system by up to a few per cent. The Sm-Nd system seems generally immune to these effects. Pseudosection analysis and conventional garnet geochronology, which presume complete matrix equilibration during metamorphism, may require modification to account for differences between whole-rock v. reactive matrix compositions

Accelerating antiviral drug discovery: lessons from COVID-19

During the coronavirus disease 2019 (COVID-19) pandemic, a wave of rapid and collaborative drug discovery efforts took place in academia and industry, culminating in several therapeutics being discovered, approved and deployed in a 2-year time frame. This article summarizes the collective experience of several pharmaceutical companies and academic collaborations that were active in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral discovery. We outline our opinions and experiences on key stages in the small-molecule drug discovery process: target selection, medicinal chemistry, antiviral assays, animal efficacy and attempts to pre-empt resistance. We propose strategies that could accelerate future efforts and argue that a key bottleneck is the lack of quality chemical probes around understudied viral targets, which would serve as a starting point for drug discovery. Considering the small size of the viral proteome, comprehensively building an arsenal of probes for proteins in viruses of pandemic concern is a worthwhile and tractable challenge for the community

A new approach for developing continuous age-depth models from dispersed chronologic data: applications to the Miocene Santa Cruz formation, Argentina

Traditional methods (linear regression, spline fitting) of age-depth modeling generate overly optimistic confidence intervals. Originally developed for C, Bayesian models (use of observations independent of chronology) allow the incorporation of prior information about superposition of dated horizons, stratigraphic position of undated points, and variations in sedimentology and sedimentation rate into model fitting. We modified the methodology of two Bayesian age depth models, Bchron (Haslett and Parnell, 2008) and OxCal (Ramsey, 2008) for use with U-Pb dates. Some practical implications of this approach include: a) model age uncertainties increase in intervals that lack closely spaced age constraints; b) models do not assume normal distributions, allowing for the non-symmetric uncertainties of sometimes complex crystal age probability functions in volcanic tuffs; c) superpositional constraints can objectively reject some cases of zircon inheritance and mitigate apparent age complexities. We use this model to produce an age-depth model with continuous and realistic uncertainties, for the early Miocene Santa Cruz Formation (SCF), Argentina.Facultad de Ciencias Naturales y Muse

A new approach for developing continuous age-depth models from dispersed chronologic data: applications to the Miocene Santa Cruz formation, Argentina

Traditional methods (linear regression, spline fitting) of age-depth modeling generate overly optimistic confidence intervals. Originally developed for C, Bayesian models (use of observations independent of chronology) allow the incorporation of prior information about superposition of dated horizons, stratigraphic position of undated points, and variations in sedimentology and sedimentation rate into model fitting. We modified the methodology of two Bayesian age depth models, Bchron (Haslett and Parnell, 2008) and OxCal (Ramsey, 2008) for use with U-Pb dates. Some practical implications of this approach include: a) model age uncertainties increase in intervals that lack closely spaced age constraints; b) models do not assume normal distributions, allowing for the non-symmetric uncertainties of sometimes complex crystal age probability functions in volcanic tuffs; c) superpositional constraints can objectively reject some cases of zircon inheritance and mitigate apparent age complexities. We use this model to produce an age-depth model with continuous and realistic uncertainties, for the early Miocene Santa Cruz Formation (SCF), Argentina.Facultad de Ciencias Naturales y Muse

Spatial and Temporal Scales of Sverdrup Balance

Sverdrup balance underlies much of the theory of ocean circulation and provides a potential tool for describing the interior ocean transport from only the wind stress. Using both a model state estimate and an eddy-permitting coupled climate model, this study assesses to what extent and over what spatial and temporal scales Sverdrup balance describes the meridional transport. The authors find that Sverdrup balance holds to first order in the interior subtropical ocean when considered at spatial scales greater than approximately 5°. Outside the subtropics, in western boundary currents and at short spatial scales, significant departures occur due to failures in both the assumptions that there is a level of no motion at some depth and that the vorticity equation is linear. Despite the ocean transport adjustment occurring on time scales consistent with the basin-crossing times for Rossby waves, as predicted by theory, Sverdrup balance gives a useful measure of the subtropical circulation after only a few years. This is because the interannual transport variability is small compared to the mean transports. The vorticity input to the deep ocean by the interaction between deep currents and topography is found to be very large in both models. These deep transports, however, are separated from upper-layer transports that are in Sverdrup balance when considered over large scales

Potential enhanced ability of giant squid to detect sperm whales is an exaptation tied to their large body size

It has been hypothesized that sperm whale predation is the driver of eye size evolution in giant squid. Given that the eyes of giant squid have the size expected for a squid this big, it is likely that any enhanced ability of giant squid to detect whales is an exaptation tied to their body size. Future studies should target the mechanism behind the evolution of large body size, not eye size. Reconstructions of the evolutionary history of selective regime, eye size, optical performance, and body size will improve the understanding of the evolution of large eyes in large ocean animals

Ringed sideroblasts in βâ thalassemia

Symptomatic βâ thalassemia is one of the globally most common inherited disorders. The initial clinical presentation is variable. Although common hematological analyses are typically sufficient to diagnose the disease, sometimes the diagnosis can be more challenging. We describe a series of patients with βâ thalassemia whose diagnosis was delayed, required bone marrow examination in one affected member of each family, and revealed ringed sideroblasts, highlighting the association of this morphological finding with these disorders. Thus, in the absence of characteristic congenital sideroblastic mutations or causes of acquired sideroblastic anemia, the presence of ringed sideroblasts should raise the suspicion of βâ thalassemia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136352/1/pbc26324.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136352/2/pbc26324_am.pd