Value of T2 Mapping MRI for Prostate Cancer Detection and Classification.

Currently, multi-parametric prostate MRI (mpMRI) consists of a qualitative T <sub>2</sub> , diffusion weighted, and dynamic contrast enhanced imaging. Quantification of T <sub>2</sub> imaging might further standardize PCa detection and support artificial intelligence solutions. To evaluate the value of T <sub>2</sub> mapping to detect prostate cancer (PCa) and to differentiate PCa aggressiveness. Retrospective single center cohort study. Forty-four consecutive patients (mean age 67 years; median PSA 7.9 ng/mL) with mpMRI and verified PCa by subsequent targeted plus systematic MR/ultrasound (US)-fusion biopsy from February 2019 to December 2019. Standardized mpMRI at 3 T with an additionally acquired T <sub>2</sub> mapping sequence. Primary endpoint was the analysis of quantitative T <sub>2</sub> values and contrast differences/ratios (CD/CR) between PCa and benign tissue. Secondary objectives were the correlation between T <sub>2</sub> values, ISUP grade, apparent diffusion coefficient (ADC) value, and PI-RADS, and the evaluation of thresholds for differentiating PCa and clinically significant PCa (csPCa). Mann-Whitney test, Spearman's rank (r <sub>s</sub> ) correlation, receiver operating curves, Youden's index (J), and AUC were performed. Statistical significance was defined as P < 0.05. Median quantitative T <sub>2</sub> values were significantly lower for PCa in PZ (85 msec) and PCa in TZ (75 msec) compared to benign PZ (141 msec) or TZ (97 msec) (P < 0.001). CD/CR between PCa and benign PZ (51.2/1.77), respectively TZ (19.8/1.29), differed significantly (P < 0.001). The best T <sub>2</sub> -mapping threshold for PCa/csPCa detection was for TZ 81/86 msec (J = 0.929/1.0), and for PZ 110 msec (J = 0.834/0.905). Quantitative T <sub>2</sub> values of PCa did not correlate significantly with the ISUP grade (r <sub>s</sub> = 0.186; P = 0.226), ADC value (r <sub>s</sub> = 0.138; P = 0.372), or PI-RADS (r <sub>s</sub> = 0.132; P = 0.392). Quantitative T <sub>2</sub> values could differentiate PCa in TZ and PZ and might support standardization of mpMRI of the prostate. Different thresholds seem to apply for PZ and TZ lesions. However, in the present study quantitative T <sub>2</sub> values were not able to indicate PCa aggressiveness. 2 TECHNICAL EFFICACY: Stage 2

First results from the CERN Axion Solar Telescope (CAST)

Hypothetical axion-like particles with a two-photon interaction would be produced in the Sun by the Primakoff process. In a laboratory magnetic field (``axion helioscope'') they would be transformed into X-rays with energies of a few keV. Using a decommissioned LHC test magnet, CAST has been running for about 6 months during 2003. The first results from the analysis of these data are presented here. No signal above background was observed, implying an upper limit to the axion-photon coupling < 1.16 10^{-10} GeV^-1 at 95% CL for m_a <~0.02 eV. This limit is comparable to the limit from stellar energy-loss arguments and considerably more restrictive than any previous experiment in this axion mass range.Comment: 4 pages, accepted by PRL. Final version after the referees comment

Mutations in the Gene DNAJC5 Cause Autosomal Dominant Kufs Disease in a Proportion of Cases: Study of the Parry Family and 8 Other Families

Background: The Neuronal Ceroid Lipofuscinoses (NCL) comprise at least nine progressive neurodegenerative genetic disorders. Kufs disease, an adult-onset form of NCL may be recessively or dominantly inherited. Our study aimed to identify genetic mutations associated with autosomal dominant Kufs disease (ADKD). Methodology and Principal Findings We have studied the family first reported with this phenotype in the 1970s, the Parry family. The proband had progressive psychiatric manifestations, seizures and cognitive decline starting in her mid 20s. Similarly affected relatives were observed in seven generations. Several of the affected individuals had post-mortem neuropathological brain study confirmatory for NCL disease. We conducted whole exome sequencing of three affected family members and identified a pLeu116del mutation in the gene DNAJC5, which segregated with the disease phenotype. An additional eight unrelated affected individuals with documented autosomal dominant or sporadic inheritance were studied. All had diagnostic confirmation with neuropathological studies of brain tissue. Among them we identified an additional individual with a p.Leu115Arg mutation in DNAJC5. In addition, a pAsn477Ser change in the neighboring gene PRPF6, a gene previously found to be associated with retinitis pigmentosa, segregated with the ADKD phenotype. Interestingly, two individuals of the Parry family did report visual impairment. Conclusions: Our study confirmed the recently reported association of DNAJC5 mutations with ADKD in two out of nine well-defined families. Sequence changes in PRPF6 have not been identified in other unrelated cases. The association of vision impairment with the expected PRPF6 dysfunction remains possible but would need further clinical studies in order to confirm the co-segregation of the visual impairment with this sequence change

Classifying aerosol type using in situ surface spectral aerosol optical properties

Knowledge of aerosol size and composition is important for determining radiative forcing effects of aerosols, identifying aerosol sources and improving aerosol satellite retrieval algorithms. The ability to extrapolate aerosol size and composition, or type, from intensive aerosol optical properties can help expand the current knowledge of spatiotemporal variability in aerosol type globally, particularly where chemical composition measurements do not exist concurrently with optical property measurements. This study uses medians of the scattering Ångström exponent (SAE), absorption Ångström exponent (AAE) and single scattering albedo (SSA) from 24 stations within the NOAA/ESRL Federated Aerosol Monitoring Network to infer aerosol type using previously published aerosol classification schemes. Three methods are implemented to obtain a best estimate of dominant aerosol type at each station using aerosol optical properties. The first method plots station medians into an AAE vs. SAE plot space, so that a unique combination of intensive properties corresponds with an aerosol type. The second typing method expands on the first by introducing a multivariate cluster analysis, which aims to group stations with similar optical characteristics and thus similar dominant aerosol type. The third and final classification method pairs 3-day backward air mass trajectories with median aerosol optical properties to explore the relationship between trajectory origin (proxy for likely aerosol type) and aerosol intensive parameters, while allowing for multiple dominant aerosol types at each station. The three aerosol classification methods have some common, and thus robust, results. In general, estimating dominant aerosol type using optical properties is best suited for site locations with a stable and homogenous aerosol population, particularly continental polluted (carbonaceous aerosol), marine polluted (carbonaceous aerosol mixed with sea salt) and continental dust/biomass sites (dust and carbonaceous aerosol); however, current classification schemes perform poorly when predicting dominant aerosol type at remote marine and Arctic sites and at stations with more complex locations and topography where variable aerosol populations are not well represented by median optical properties. Although the aerosol classification methods presented here provide new ways to reduce ambiguity in typing schemes, there is more work needed to find aerosol typing methods that are useful for a larger range of geographic locations and aerosol populations

Equivocal pi-rads three lesions on prostate magnetic resonance imaging: Risk stratification strategies to avoid mri-targeted biopsies

We aimed to investigate the relation between largest lesion diameter, prostate-specific antigen density (PSA-D), age, and the detection of clinically significant prostate cancer (csPCa) using first-time targeted biopsy (TBx) in men with Prostate Imaging—Reporting and Data System (PI-RADS) 3 index lesions. A total of 292 men (2013–2019) from two referral centers were included. A multivariable logistic regression analysis was performed. The discrimination and clinical utility of the built model was assessed by the area under the receiver operation curve (AUC) and decision curve analysis, respectively. A higher PSA-D and higher age were significantly related to a higher risk of detecting csPCa, while the largest index lesion diameter was not. The discrimination of the model was 0.80 (95% CI 0.73–0.87). When compared to a biopsy-all strategy, decision curve analysis showed a higher net benefit at threshold probabilities of ≥2%. Accepting a missing ≤5% of csPCa diagnoses, a risk-based approach would result in 34% of TBx sessions and 23% of low-risk PCa diagnoses being avoided. In men with PI-RADS 3 index lesions scheduled for first-time TBx, the balance between the number of TBx sessions, the detection of low-risk PCa, and the detection of csPCa does not warrant a biopsy-all strategy. To minimize the risk of missing the diagnosis of csPCa but acknowledging the need of avoiding unnecessary TBx sessions and overdiagnosis, a risk-based approach is advisable

The search for solar axions in the CAST experiment

The CAST (CERN Axion Solar Telescope) experiment at CERN searches for solar axions with energies in the keV range. It is possible that axions are produced in the core of the sun by the interaction of thermal photons with virtual photons of strong electromagnetic fields. In this experiment, the solar axions can be reconverted to photons in the transversal field of a 9 Tesla superconducting magnet. At both ends of the 10m-long dipole magnet three different X-ray detectors were installed, which are sensitive in the interesting photon energy range. Preliminary results from the analysis of the 2004 data are presented: g$_{a\gamma}<0.9\times10^{-10}$ GeV$^{-1}$ at 95% C.L. for axion masses m$_{a} <$ 0.02 eV. At the end of 2005, data started to be taken with a buffer gas in the magnet pipes in order to extend the sensitivity to axion masses up to 0.8 eV.The CAST (CERN Axion Solar Telescope) experiment at CERN searches for solar axions with energies in the keV range. It is possible that axions are produced in the core of the sun by the interaction of thermal photons with virtual photons of strong electromagnetic fields. In this experiment, the solar axions can be reconverted to photons in the transversal field of a 9 Tesla superconducting magnet. At both ends of the 10m-long dipole magnet three different X-ray detectors were installed, which are sensitive in the interesting photon energy range. Preliminary results from the analysis of the 2004 data are presented: g$_{a\gamma}<0.9\times10^{-10}$ GeV$^{-1}$ at 95% C.L. for axion masses m$_{a} <$ 0.02 eV. At the end of 2005, data started to be taken with a buffer gas in the magnet pipes in order to extend the sensitivity to axion masses up to 0.8 eV

Search for solar axions: CAST

The CERN Axion Solar Telescope (CAST) is searching for axions produced in the Sun's core by the Primakoff process. CAST is using a decommissioned Large Hadron Collider (LHC) test magnet where axions could be converted back into X-rays with energies up to 10 keV. Analysis of the 2003 data showed no signal above background implying an upper limit for the axion-photon coupling constant gagg < 1.16 X 10 ^-10 GeV exp -1 at 95% C.L. for ma . 0.02 eV [1]. The higher quality 2004 data is presently under analysis. CAST Phase II is scheduled to start in late 2005. This will be the first step in extending CAST's sensitivity to axion rest masses up to ~ 1 eV

An Essential Role for Katanin p80 and Microtubule Severing in Male Gamete Production

Katanin is an evolutionarily conserved microtubule-severing complex implicated in multiple aspects of microtubule dynamics. Katanin consists of a p60 severing enzyme and a p80 regulatory subunit. The p80 subunit is thought to regulate complex targeting and severing activity, but its precise role remains elusive. In lower-order species, the katanin complex has been shown to modulate mitotic and female meiotic spindle dynamics and flagella development. The in vivo function of katanin p80 in mammals is unknown. Here we show that katanin p80 is essential for male fertility. Specifically, through an analysis of a mouse loss-of-function allele (the Taily line), we demonstrate that katanin p80, most likely in association with p60, has an essential role in male meiotic spindle assembly and dissolution and the removal of midbody microtubules and, thus, cytokinesis. Katanin p80 also controls the formation, function, and dissolution of a microtubule structure intimately involved in defining sperm head shaping and sperm tail formation, the manchette, and plays a role in the formation of axoneme microtubules. Perturbed katanin p80 function, as evidenced in the Taily mouse, results in male sterility characterized by decreased sperm production, sperm with abnormal head shape, and a virtual absence of progressive motility. Collectively these data demonstrate that katanin p80 serves an essential and evolutionarily conserved role in several aspects of male germ cell development

Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation

A novel method for quantifying the similarity between phenotypes by the use of ontologies can be used to search for candidate genes, pathway members, and human disease models on the basis of phenotypes alone