140 research outputs found
Sensitivity to measurement perturbation of single atom dynamics in cavity QED
We consider continuous observation of the nonlinear dynamics of single atom
trapped in an optical cavity by a standing wave with intensity modulation. The
motion of the atom changes the phase of the field which is then monitored by
homodyne detection of the output field. We show that the conditional Hilbert
space dynamics of this system, subject to measurement induced perturbations,
depends strongly on whether the corresponding classical dynamics is regular or
chaotic. If the classical dynamics is chaotic the distribution of conditional
Hilbert space vectors corresponding to different observation records tends to
be orthogonal. This is a characteristic feature of hypersensitivity to
perturbation for quantum chaotic systems.Comment: 11 pages, 6 figure
Accommodating heterogeneous missing data patterns for prostate cancer risk prediction
Objective: We compared six commonly used logistic regression methods for
accommodating missing risk factor data from multiple heterogeneous cohorts, in
which some cohorts do not collect some risk factors at all, and developed an
online risk prediction tool that accommodates missing risk factors from the
end-user. Study Design and Setting: Ten North American and European cohorts
from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a
risk prediction tool for clinically significant prostate cancer, defined as
Gleason grade group greater or equal 2 on standard TRUS prostate biopsy. One
large European PBCG cohort was withheld for external validation, where
calibration-in-the-large (CIL), calibration curves, and
area-underneath-the-receiver-operating characteristic curve (AUC) were
evaluated. Ten-fold leave-one-cohort-internal validation further validated the
optimal missing data approach. Results: Among 12,703 biopsies from 10 training
cohorts, 3,597 (28%) had clinically significant prostate cancer, compared to
1,757 of 5,540 (32%) in the external validation cohort. In external validation,
the available cases method that pooled individual patient data containing all
risk factors input by an end-user had best CIL, under-predicting risks as
percentages by 2.9% on average, and obtained an AUC of 75.7%. Imputation had
the worst CIL (-13.3%). The available cases method was further validated as
optimal in internal cross-validation and thus used for development of an online
risk tool. For end-users of the risk tool, two risk factors were mandatory:
serum prostate-specific antigen (PSA) and age, and ten were optional: digital
rectal exam, prostate volume, prior negative biopsy,
5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic
ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer
family history
Search for residual prostate cancer on pT0 radical prostatectomy after positive biopsy
Reported incidence of no residual prostate cancer (i.e. pathological stage pT0) on radical prostatectomy ranges from 0.07 to 4.2%. The incidence is higher after neoadjuvant endocrine treatment. The aim of this study was to search for residual cancer on radical prostatectomy (RP) specimens when an initial sampling failed to find the cancer in patients with positive biopsy. Our database of 1,328 consecutive patients whose biopsies and RP specimen were both examined at the Polytechnic University-United Hospitals of the Marche Region between March 1995 and June 2006 was reviewed. The radical prostatectomies were grossly completely sampled and examined with the whole mount technique. We identified eight patients (i.e. 0.6%; three untreated and five hormonally treated preoperatively, i.e. 0.3 and 0.8%, respectively, of the total number of RPs included in the study) with positive biopsy and with no residual cancer in the initial routine histological examination of the RP. The RP of this group of eight was subjected to additional sectioning and evaluation of the paraffin blocks of the prostatectomy, also after block-flipping, immunostaining with an antibody against CAM 5.2, p63, PSA, and alpha-methylacyl-CoA racemase, and DNA specimen identity analysis. There were no cases with a false positive biopsy diagnosis, and cancer was not overlooked or missed in the initial routine histological examination of any of the 8 pT0 RPs. A minute focus of cancer (the diameter was always below 2.0Â mm) was found on the additional sections in five. In particular, cancer was found after block-flipping in one of them. In an additional case, cancer was eventually discovered after immunostaining tissue sections for cytokeratin CAM 5.2, for p63 and PSA. In the remaining two cases (one untreated and the other hormonally treated), cancer was not found (0.15% of the 1,328 RPs included in the study); the review of the description of the macroscopic appearance of the RP and of its slides revealed that part of the peripheral zone corresponding to the site of the positive biopsy was missing, i.e. not removed from the patient at the time of the operation at least in one of the two. DNA specimen analysis confirmed the identity of the biopsy and prostatectomy in both. An extensive search for residual cancer reduces the number of pT0 RPs after a positive biopsy from 0.6 to 0.15%. It is recommended to have the needle biopsy reviewed, carefully look again at the radical prostatectomy, do deeper sections and then flip certain paraffin blocks. In addition, atypical foci should be stained for basal cell markers and often AMACR, especially in hormone-treated cases. If a block is missing part of the peripheral zone (capsular incision), this should be commented on. DNA analysis for tissue identity should be performed when the other steps have been taken without finding cancer
A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data
Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. /
Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score â„7, stage T3âT4, PSA â„10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. /
Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. /
Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. /
Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions
Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG
BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatelliteâbased linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LODââ„â1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genomeâwide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37âcM interval on 4q13â25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC , an important gene in PC biology. CONCLUSIONS These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer. Prostate 72:410â426, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90245/1/21443_ftp.pd
National CO2 budgets (2015â2020) inferred from atmospheric CO2 observations in support of the Global Stocktake
Accurate accounting of emissions and removals of CO2 is critical for the planning and verification of emission reduction targets in support of the Paris Agreement. Here, we present a pilot dataset of country-specific net carbon exchange (NCE; fossil plus terrestrial ecosystem fluxes) and terrestrial carbon stock changes aimed at informing countriesâ carbon budgets. These estimates are based on "top-down" NCE outputs from the v10 Orbiting Carbon Observatory (OCO-2) modeling intercomparison project (MIP), wherein an ensemble of inverse modeling groups conducted standardized experiments assimilating OCO-2 column-averaged dry-air mole fraction (XCO2) retrievals (ACOS v10), in situ CO2 measurements, or combinations of these data. The v10 OCO-2 MIP NCE estimates are combined with "bottom-up" estimates of fossil fuel emissions and lateral carbon fluxes to estimate changes in terrestrial carbon stocks, which are impacted by anthropogenic and natural drivers. These flux and stock change estimates are reported annually (2015â2020) as both a global 1° Ă 1° gridded dataset and as a country-level dataset. Across the v10 OCO-2 MIP experiments, we obtain increases in the ensemble median terrestrial carbon stocks of 3.29â4.58 PgCO2 yr-1 (0.90â1.25 PgC yr-1). This is a result of broad increases in terrestrial carbon stocks across the northern extratropics, while the tropics generally have stock losses but with considerable regional variability and differences between v10 OCO-2 MIP experiments. We discuss the state of the science for tracking emissions and removals using top-down methods, including current limitations and future developments towards top-down monitoring and verification systems
Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.
OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score â„7, stage T3-T4, PSA (prostate specific antigen) concentration â„10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. SETTING: Multiple institutions that were members of international PRACTICAL consortium. PARTICIPANTS: All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31â747 men; the validation dataset comprised 6411 men. MAIN OUTCOME MEASURES: Prediction with hazard score of age of onset of aggressive cancer in validation set. RESULTS: In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. CONCLUSIONS: Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa
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