Genetic Analysis of Larval Dispersal, Gene Flow, and Connectivity

Genetic data can be used to characterize the scale or magnitude of connectivity via larval dispersal in the plankton as the per capita migration rate (m), the rate of gene flow (Nm), or counts of immigrant individuals. Population-based methods infer average effective rates of connectivity on long time scales (hundreds to thousands of generations), and those estimates will influenced by many processes (including larval dispersal). Individual-based methods based on clustering or assignment of individual genotypes to populations or families are suitable for estimating connectivity on short timescales. The typical or characteristic larval dispersal distance for any one system of populations may best be characterized by isolation-by-distance patterns (using population model methods) or by the dispersal kernel (using parentage-based methods). Migration rates estimated from individual-based methods may be more relevant to ecological studies of demographic connectivity (e.g., among demes in a network of marine prote ted areas) compared to rates of gene flow estimated from population-based methods

Prospective comparison of F-18-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer

Purpose To prospectively compare F-18-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). Methods Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-18-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. Results Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-18-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. Conclusion F-18-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.Peer reviewe

A Prospective Comparison of F-18-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE)

Background: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). Objective: To compare standard staging modalities with newer and potentially more accurate imaging modalities. Design, setting, and participants: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group >= 3 and/or prostate-specific antigen [PSA] >= 20 and/or cT >= T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. Outcome measurements and statistical analysis: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, Tc-99m-hydroxymethylene diphosphonate (Tc-99m-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and F-18-prostate-specific membrane antigen-1007 (F-18-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. Results and limitations: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality F-18-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method F-18-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. Conclusions: Despite the risk of false positive bone lesions, F-18-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. Patient summary: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that F-18-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (F-18-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.Peer reviewe

Evidence of Υ(1S)→J/ψ+χc1\Upsilon(1S) \to J/\psi+\chi_{c1} and search for double-charmonium production in Υ(1S)\Upsilon(1S) and Υ(2S)\Upsilon(2S) decays

Using data samples of $102\times10^6$ $\Upsilon(1S)$ and $158\times10^6$ $\Upsilon(2S)$ events collected with the Belle detector, a first experimental search has been made for double-charmonium production in the exclusive decays $\Upsilon(1S,2S)\rightarrow J/\psi(\psi')+X$, where $X=\eta_c$, $\chi_{cJ} (J=~0,~1,~2)$, $\eta_c(2S)$, $X(3940)$, and $X(4160)$. No significant signal is observed in the spectra of the mass recoiling against the reconstructed $J/\psi$ or $\psi'$ except for the evidence of $\chi_{c1}$ production with a significance of $4.6\sigma$ for $\Upsilon(1S)\rightarrow J/\psi+\chi_{c1}$. The measured branching fraction \BR(\Upsilon(1S)\rightarrow J/\psi+\chi_{c1}) is $(3.90\pm1.21(\rm stat.)\pm0.23 (\rm syst.))\times10^{-6}$. The $90\%$ confidence level upper limits on the branching fractions of the other modes having a significance of less than $3\sigma$ are determined. These results are consistent with theoretical calculations using the nonrelativistic QCD factorization approach.Comment: 12 pages, 4 figures, 1 table. The fit range was extended to include X(4160) signal according to referee's suggestions. Other results unchanged. Paper was accepted for publication as a regular article in Physical Review

Unfolding the Secrets of Small Cell Lung Cancer Progression: Novel Approaches and Insights Through Rapid Autopsies

The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms

A prospective, active haemovigilance study with combined cohort analysis of 19 175 transfusions of platelet components prepared with amotosalen-UVA photochemical treatment

Background and Objectives: A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT™ Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated platelet components (PCT-PLT) administered across a broad patient population. Materials and Methods: This open-label, observational haemovigilance programme of PCT-PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post-transfusion and for serious adverse events (SAEs) up to 7 days post-transfusion. All adverse events were assessed for severity (Grade 0–4), and causal relationship to PCT-PLT transfusion. Results: Over the course of 7 years in the study centres, 4067 patients received 19 175 PCT-PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per-transfusion basis, 123 (0·6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0·4%) and urticaria (41, 0·2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0·1%). No case of transfusion-related acute lung injury, transfusion-associated graft-versus-host disease, transfusion-transmitted infection or death was attributed to the transfusion of PCT-PLT. Conclusion: This longitudinal haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components.publishedVersio

The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer

Purpose To prospectively compare F-18-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa).Methods Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-18-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used.Results Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-18-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively.Conclusion F-18-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.</div

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO