The noise performance of electron-multiplying charge-coupled devices at X-ray energies

Electron-multiplying charge-coupled devices (EMCCDs) are used in low-light-level (L3) applications for detecting optical, ultraviolet, and near-infrared photons (10–1100 nm). The on-chip gain process is able to increase the detectability of any signal collected by the device through the multiplication of the signal before the output node. Thus, the effective readout noise can be reduced to subelectron levels, allowing the detection of single photons. However, this gain process introduces an additional noise component due to the stochastic nature of the multiplication. In optical applications, this additional noise has been characterized. The broadening of the detected peak is described by the excess noise factor. This factor tends to a value of √2 at high gain (>100x). In X-ray applications, the situation is improved by the effect that Fano factor f has on the shot noise associated with X-ray photon detection (f ≈ 0.12 at X-ray energies). In this paper, the effect of the detection of X-ray photons in silicon is assessed both analytically and through a Monte Carlo model of the gain amplification process. The excess noise on the signal is predicted (termed the modified Fano factor) for photon detection in an EM-CCD at X-ray energies. A hypothesis is made that the modified Fano factor should tend to 1.115 at high levels of gain (>10x). In order to validate the predictions made, measurements were taken using an 55 Fe source with Mn k-alpha X-ray energy of 5898 eV. These measurements allowed the hypothesis to be verified

The noise performance of electron-multiplying charge-coupled devices at soft X-ray energy values

The use of electron-multiplying charge-coupled devices (CCDs) for high-resolution soft X-ray spectroscopy has been proposed in previous studies, and the analysis that followed experimentally identified and verified a modified Fano factor for X-ray detection using an 55Fe X-ray source. However, further experiments with soft X-rays at 1000 eV were less successful, attributed to excessive split events. More recently, through the use of deep-depletion e2v CCD220 and on-chip binning, it has been possible to greatly reduce the number of split events, allowing the result for the modified Fano factor at soft X-ray energy values to be verified. This paper looks at the earlier attempt to verify the modified Fano factor at 1000 eV with e2v CCD97 and shows the issues created by splitting of the charge cloud between pixels. It then compares these earlier results with new data collected using e2v CCD220, investigating how split-event reduction allows the modified Fano factor to be verified for low-energy X-rays

Class dynamics of development: a methodological note

This article argues that class relations are constitutive of developmental processes and central to understanding inequality within and between countries. In doing so it illustrates and explains the diversity of the actually existing forms of class relations, and the ways in which they interplay with other social relations such as gender and ethnicity. This is part of a wider project to re- vitalise class analysis in the study of development problems and experiences

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer

Background: Observational studies have associated adiposity with an increased risk of colorectal cancer (CRC). However, such studies do not establish a causal relationship. To minimise bias from confounding we performed a Mendelian randomisation (MR) analysis to examine the relationship between adiposity and CRC. Methods: We used SNPs associated with adult body mass index (BMI), waist-hip ratio (WHR), childhood obesity and birth weight as instrumental variables in a MR analysis of 9254 CRC cases and 18 386 controls. Results: In the MR analysis, the odds ratios (ORs) of CRC risk per unit increase in BMI, WHR and childhood obesity were 1.23 (95% CI: 1.02-1.49, P = 0.033), 1.59 (95% CI: 1.08-2.34, P = 0.019) and 1.07 (95% CI: 1.03-1.13, P = 0.018), respectively. There was no evidence for association between birth weight and CRC (OR = 1.22, 95% CI: 0.89-1.67, P = 0.22). Combining these data with a concurrent MR-based analysis for BMI and WHR with CRC risk (totalling to 18 190 cases, 27 617 controls) provided increased support, ORs for BMI and WHR were 1.26 (95% CI: 1.10-1.44, P = 7.7 x 10(-4)) and 1.40 (95% CI: 1.14-1.72, P = 1.2 x 10(-3)), respectively. Conclusions: These data provide further evidence for a strong causal relationship between adiposity and the risk of developing CRC highlighting the urgent need for prevention and treatment of adiposity.Peer reviewe

Off-plane x-ray grating spectrometer camera for IXO

The International X-ray Observatory (IXO) is a merger of the former ESA XEUS and NASA Constellation-X missions, with additional collaboration from JAXA, proposed for launch ~2020. IXO will address the leading astrophysical questions in the ‘hot universe’ through its breakthrough capabilities in X-ray spectroscopy. The mission covers the 0.1 to 40 keV energy range, complementing the capabilities of the next generation observatories, such as ALMA, LSST, JWST and 30 meter ground-based telescopes. An X-ray Grating Spectrometer is baselined to provide science in the energy range 0.3-1.0 keV at a spectral resolution of E/ΔE > 3,000 with an effective area greater than 1,000 cm2. This will require an array of soft X-ray enhanced CCDs operating at a modest frame rate to measure the diffracted light in both position and energy. Here we describe the baseline camera for the off-plane XGS instrument using mature CCD technology

Decentralization and democracy in Indonesia: A critique of neo-institutionalist perspectives

10.1111/j.0012-155X.2004.00376.xDevelopment and Change354697-71

Ductal adenocarcinoma of the prostate: A systematic review and meta-analysis of incidence, presentation, prognosis, and management

Context Ductal adenocarcinoma (DAC) is relatively rare, but is nonetheless the second most common subtype of prostate cancer. First described in 1967, opinion is still divided regarding its biology, prognosis, and outcome. Objectives To systematically interrogate the literature to clarify the epidemiology, diagnosis, management, progression, and survival statistics of DAC. Materials and methods We conducted a literature search of five medical databases from inception to May 04 2020 according to PRISMA criteria using search terms “prostate ductal adenocarcinoma” OR “endometriod adenocarcinoma of prostate” and variations of each. Results Some 114 studies were eligible for inclusion, presenting 2 907 170 prostate cancer cases, of which 5911 were DAC. [Correction added on 16 January 2021 after the first online publication: the preceding statement has been corrected in this current version.] DAC accounts for 0.17% of prostate cancer on meta‐analysis (range 0.0837%‐13.4%). The majority of DAC cases were admixed with predominant acinar adenocarcinoma (AAC). Median Prostate Specific Antigen at diagnosis ranged from 4.2 to 9.6 ng/mL in the case series. DAC was more likely to present as T3 (RR1.71; 95%CI 1.53‐1.91) and T4 (RR7.56; 95%CI 5.19‐11.01) stages, with far higher likelihood of metastatic disease (RR4.62; 95%CI 3.84‐5.56; all P‐values < .0001), compared to AAC. Common first treatments included surgery (radical prostatectomy (RP) or cystoprostatectomy for select cases) or radiotherapy (RT) for localized disease, and hormonal or chemo‐therapy for metastatic disease. Few studies compared RP and RT modalities, and those that did present mixed findings, although cancer‐specific survival rates seem worse after RP. Biochemical recurrence rates were increased with DAC compared to AAC. Additionally, DAC metastasized to unusual sites, including penile and peritoneal metastases. Where compared, all studies reported worse survival for DAC compared to AAC. Conclusion When drawing conclusions about DAC it is important to note the heterogenous nature of the data. DAC is often diagnosed incidentally post‐treatment, perhaps due to lack of a single, universally applied histopathological definition. As such, DAC is likely underreported in clinical practice and the literature. Poorer prognosis and outcomes for DAC compared to AAC merit further research into genetic composition, evolution, diagnosis, and treatment of this surprisingly common prostate cancer sub‐type. Patient summary Ductal prostate cancer is a rare but important form of prostate cancer. This review demonstrates that it tends to be more serious at detection and more likely to spread to unusual parts of the body. Overall survival is worse with this type of prostate cancer and urologists need to be aware of the presence of ductal prostate cancer to alter management decisions and follow‐up.</p

Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in the Detection of Clinically Significant Prostate Cancer in the Prostate Imaging Reporting and Data System Era: A Systematic Review and Meta-analysis.

CONTEXT: 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. OBJECTIVE: 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). EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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%). CONCLUSIONS: 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. PATIENT SUMMARY: 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