Typical values of z-resolution for different Digital Breast Tomosynthesis systems evaluated in a multicenter study.

PURPOSE: The aim of the present study, conducted by a working group of the Italian Association of Medical Physics (AIFM), was to define typical z-resolution values for different digital breast tomosynthesis (DBT) models to be used as a reference for quality control (QC). Currently, there are no typical values published in internationally agreed QC protocols. METHODS: To characterize the z-resolution of the DBT models, the full width at half maximum (FWHM) of the artifact spread function (ASF), a technical parameter that quantifies the signal intensity of a detail along reconstructed planes, was analyzed. Five different commercial phantoms, CIRS Model 011, CIRS Model 015, Modular DBT phantom, Pixmam 3-D, and Tomophan, were evaluated on reconstructed DBT images and 82 DBT systems (6 vendors, 9 models) in use at 39 centers in Italy were involved. RESULTS: The ASF was found to be dependent on the detail size, the DBT angular acquisition range, the reconstruction algorithm and applied image processing. In particular, a progressively greater signal spread was observed as the detail size increased and the acquisition angle decreased. However, a clear correlation between signal spread and angular range width was not observed due to the different signal reconstruction and image processing strategies implemented in the algorithms developed by the vendors studied. CONCLUSIONS: The analysis led to the identification of typical z-resolution values for different DBT model-phantom configurations that could be used as a reference during a QC program.

A Psychometric Study of a Trait and State Assessment of Sexual Pleasure - The Amsterdam Sexual Pleasure Inventory.

We studied the Amsterdam Sexual Pleasure Inventory's (1.0) psychometric properties. The ASPI, a revised self-report battery designed to measure domains of state and trait sexual pleasure in diverse gender, sex, and relationship populations, is based on a recently proposed conceptual framework of sexual pleasure. We collected quantitative (n = 1371) and qualitative data (n = 637) using a cross-sectional multi-method design targeting the general (German-speaking) population. After pre-processing, we conducted analyses on a sample of n = 706 participants. The theory-based 5-factor exploratory structural equation model and the principal component analyses of the two general exploratory index-scales showed good and acceptable structural validity evidence respectively. Measurement invariance was confirmed separately for male and female participants and for those with sexually functional-scoring and dysfunctional-scoring levels. Coefficient omega indicated that all scales, except those of one facet, showed acceptable to very good internal consistency. The ASPI's convergent and discriminant associations with sexological and psychological constructs demonstrated good overall construct validity. Participants understood the items as intended and felt that the ASPI covered relevant facets of sexual pleasure. The ASPI might help understand how individuals differ in experiencing sexual pleasure and how different contexts enable some people to experience pleasure while disadvantaging others.

Search for Dark-Matter-Nucleon Interactions via Migdal Effect with DarkSide-50.

Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear system and allows for the detection of interactions of sub-GeV/c^{2} mass dark matter. We present new constraints for sub-GeV/c^{2} dark matter using the dual-phase liquid argon time projection chamber of the DarkSide-50 experiment with an exposure of (12 306±184) kg d. The analysis is based on the ionization signal alone and significantly enhances the sensitivity of DarkSide-50, enabling sensitivity to dark matter with masses down to 40 MeV/c^{2}. Furthermore, it sets the most stringent upper limit on the spin independent dark matter nucleon cross section for masses below 3.6 GeV/c^{2}.

Search for Dark Matter Particle Interactions with Electron Final States with DarkSide-50.

We present a search for dark matter particles with sub-GeV/c^{2} masses whose interactions have final state electrons using the DarkSide-50 experiment's (12 306±184) kg d low-radioactivity liquid argon exposure. By analyzing the ionization signals, we exclude new parameter space for the dark matter-electron cross section σ[over ¯]_{e}, the axioelectric coupling constant g_{Ae}, and the dark photon kinetic mixing parameter κ. We also set the first dark matter direct-detection constraints on the mixing angle |U_{e4}|^{2} for keV/c^{2} sterile neutrinos.

Surgeon eye lens dose monitoring in interventional neuroradiology, cardiovascular and radiology procedures.

PURPOSE: This study investigated the radiation dose to surgeon eye lens for single procedure and normalised to exposure parameters for eight selected neuroradiology, cardiovascular and radiology interventional procedures. METHODS: The procedures investigated were diagnostic study, Arteriovenous Malformations treatment (AVM) and aneurysm embolization for neuroradiology procedures, Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty (CA-PTCA), Pacemaker and Implantable Cardioverter-Defibrillator implantation (PM-ICD), Endovascular Aortic Repair (EVAR) and Fenestrated Endovascular Aortic Repair (FEVAR) for cardiovascular and electrophysiology procedures. CT-guided lung biopsy was also monitored. All procedures were performed with table-mounted and ceiling-suspended shields (0.5 mm lead equivalent thickness), except for FEVAR and PM-ICD where only a table mounted shield was present, and CT-guided lung biopsy where no shield was used. Dose assessment was performed using a dosemeter positioned close to the most exposed eye of the surgeon, outside the protective eyewear. RESULTS: The surgeon most exposed eye lens median Hp(3) equivalent dose for a single procedure, without protective eyewear contribution, was 18 µSv for neuroradiology diagnostic study, 62 µSv for AVM, 38 µSv for aneurysm embolization, 33 µSv for CA-PTCA, 39 µSv for PM-ICD, 49 µSv for EVAR, 2500 µSv for FEVAR, 153 µSv for CT-guided lung biopsy. CONCLUSIONS: In interventional procedures, the 20 mSv/year dose limit for surgeon eye lens exposure might be exceeded if shields or protective eyewear are not used. Surgeon eye lens doses, normalised to single procedures and to exposure parameters, are a valuable tool for determining appropriate radiation protection measures and dedicated eye lens dosemeter assignment.

Measurement of the Cosmic Ray Helium Energy Spectrum from 70 GeV to 80 TeV with the DAMPE Space Mission.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

Measurement of the cosmic ray proton spectrum from 40 GeV to 100 TeV with the DAMPE satellite.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

Constraints on Sub-GeV Dark-Matter-Electron Scattering from the DarkSide-50 Experiment.

We present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matter-electron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c^{2}.

Low-Mass Dark Matter Search with the DarkSide-50 Experiment.

We present the results of a search for dark matter weakly interacting massive particles (WIMPs) in the mass range below 20 GeV/c^{2} using a target of low-radioactivity argon with a 6786.0 kg d exposure. The data were obtained using the DarkSide-50 apparatus at Laboratori Nazionali del Gran Sasso. The analysis is based on the ionization signal, for which the DarkSide-50 time projection chamber is fully efficient at 0.1 keVee. The observed rate in the detector at 0.5 keVee is about 1.5 event/keVee/kg/d and is almost entirely accounted for by known background sources. We obtain a 90% C.L. exclusion limit above 1.8 GeV/c^{2} for the spin-independent cross section of dark matter WIMPs on nucleons, extending the exclusion region for dark matter below previous limits in the range 1.8-6 GeV/c^{2}.

Nuclear reaction measurements on tissue-equivalent materials and GEANT4 Monte Carlo simulations for hadrontherapy.

When a carbon beam interacts with human tissues, many secondary fragments are produced into the tumor region and the surrounding healthy tissues. Therefore, in hadrontherapy precise dose calculations require Monte Carlo tools equipped with complex nuclear reaction models. To get realistic predictions, however, simulation codes must be validated against experimental results; the wider the dataset is, the more the models are finely tuned.Since no fragmentation data for tissue-equivalent materials at Fermi energies are available in literature, we measured secondary fragments produced by the interaction of a 55.6 MeV u(-1) (12)C beam with thick muscle and cortical bone targets. Three reaction models used by the Geant4 Monte Carlo code, the Binary Light Ions Cascade, the Quantum Molecular Dynamic and the Liege Intranuclear Cascade, have been benchmarked against the collected data. In this work we present the experimental results and we discuss the predictive power of the above mentioned models.

Discovery and optimization of 2-aryl oxazolo-pyrimidines as adenosine kinase inhibitors using liquid phase parallel synthesis.

Adenosine kinase inhibition is an attractive therapeutic approach for several conditions for example, neurodegeneration, seizures, ischemia, inflammation and pain. Several nucleosidic and non-nucleosidic inhibitors are available. Using a virtual screening approach, we have discovered that 2-aryl oxazolo-pyrimidines are adenosine kinase inhibitors. Subsequent high throughput derivatization enabled the optimization of this new inhibitor chemotype resulting in highly potent derivatives. A variety of analogues were produced by applying liquid phase parallel synthesis to vary the 7-amino residues as well as the 2-aryl moiety.

The AN2 protein is a novel marker for the Schwann cell lineage expressed by immature and nonmyelinating Schwann cells.

The expression of the 330 kDa AN2 glycoprotein was studied in the rodent peripheral nervous system. AN2 is expressed by immature Schwann cells in vitro and in vivo and downregulated as the cells upregulate myelin genes. A subpopulation of nonmyelinating Schwann cells in the adult sciatic nerve retains expression of AN2. In rat sciatic nerve crushes, where Schwann cell numbers increase after initial axonal loss and markers of immature Schwann cells show an upregulation, no increased expression of AN2 was observed. In contrast, AN2 expression was upregulated in nerves from peripheral myelin protein-22-transgenic rats, where immature Schwann cells expand without axonal loss. Furthermore, coculture with neurons upregulated AN2 expression on Schwann cells in vitro. Polyclonal antibodies against AN2 inhibited the migration of an immortalized Schwann cell clone in an in vitro migration assay, and the purified AN2 protein was shown to be neither inhibitory nor permissive for outgrowing dorsal root ganglion neurites. AN2 is thus a novel marker for the Schwann cell lineage. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of purified AN2 from early postnatal mouse brain demonstrated that AN2 is the murine homolog of the rat NG2 proteoglycan.

Mutation-dependent alteration in cellular distribution of peripheral myelin protein 22 in nerve biopsies from Charcot-Marie-Tooth type 1A.

The hereditary demyelinating neuropathy Charcot-Marie-Tooth type 1A is caused by duplication or by point mutations of the PMP22 gene. Histopathological differences in these genotypes suggest distinct disease mechanisms. In the present investigation we demonstrate a pathologically altered cellular distribution of PMP22 in sural nerve biopsies of patients with PMP22 point mutations. In these patients, in contrast to findings in patients with PMP22 duplication, PMP22 partially accumulates in the Schwann cells instead of being inserted in the myelin sheath. These findings may explain the different histopathology and may suggest different mechanisms of pathogenesis in these genotypes.

Basal membrane-depleted scar in lesioned CNS: characteristics and relationships with regenerating axons.

The lesion scar formed after CNS injury is an impediment to axonal regeneration and leads to growth arrest or misrouting of sprouting axons. Our previous study showed that pharmacological reduction of basal membrane formation within the scar can overcome this scar impermeability [Stichel C. C. et al. (1999) Eur. J. Neurosci. 11, 632-646]. The aim of the present study was to characterize the basal membrane-depleted scar and to analyse its relationships with penetrating axons. The experiments comprised two groups of animals in which the left postcommissural fornix was transected; in addition, one group received a local immediate injection of the collagen IV-reducing agent dipyridyl, while the other group received an injection of phosphate-buffered saline. Immunohistochemical methods were used to characterize scar formation and scar-axon relationships. Animals receiving dipyridyl showed reduction of collagen IV-immunopositive basal membrane in the lesion center, which was accompanied by: (i) a decrease in laminin, as well as chondroitin and heparan sulfate proteoglycan, deposition in the lesion center; (ii) an increase in chondroitin and keratan sulfate proteoglycan expression in the perilesional area; (iii) a typical activation pattern of astrocytes and microglia/macrophages; (iv) axons regenerating through this modified scar were closely associated with various glial cell types and crossed a prominent chondroitin/keratan sulfate proteoglycan matrix. Our results suggest that neither the formation of a reactive astroglial network nor the accumulation of microglia/macrophages or the deposition of chondroitin and keratan sulfate proteoglycans in the perilesional area represent a barrier to regrowing axons. The present approach demonstrates that the lesion-induced basal membrane itself is the primary determinant of scar impermeability.

Progesterone derivatives are able to influence peripheral myelin protein 22 and P0 gene expression: possible mechanisms of action.

The present study has analyzed the effect of progesterone and its derivatives (dihydroprogesterone and tetrahydroprogesterone) on the gene expression of the peripheral myelin protein 22 utilizing in vivo and in vitro models. The data obtained indicate that tetrahydroprogesterone is able to stimulate the gene expression of peripheral myelin protein 22 both in vivo (in adult but not in old animals) and in Schwann cell cultures. An effect of this steroid, which is known to interact with the GABA(A) receptor, would not be surprising, since in the present study we show the presence in Schwann cells and in the sciatic nerve of the messengers for several subunits (alpha2, alpha3, beta1, beta2, and beta3) of the GABA(A) receptor. An effect of tetrahydroprogesterone is also evident on the gene expression of another myelin protein, the peripheral myelin protein zero. However, in this case also dihydroprogesterone, which is able to bind the progesterone receptor, is involved, both in old and adult animals, in the stimulation of messengers levels of this myelin protein. In conclusion, the present data show that the gene expression of two important peripheral myelin proteins can be influenced by progesterone derivatives. The hypothesis has been put forward that part of their effects might occur not through the classical progesterone receptor, but rather via an interaction with the GABA(A) receptor.

Peripheral myelin protein 22 and protein zero: a novel association in peripheral nervous system myelin.

Mutations found in the two major glycosylated transmembrane proteins of the PNS myelin, the peripheral myelin protein zero (P0) and peripheral myelin protein 22 (PMP22), have been independently associated with the most common hereditary demyelinating peripheral neuropathies. Genotype-phenotype correlations in humans and transgenic animals have provided functional evidence that P0 and PMP22 are involved in formation and maintenance of compact myelin. Here, we demonstrate for the first time that P0 and PMP22 proteins form complexes in the myelin membrane, as shown by coimmunoprecipitation experiments, and that glycosylation is not involved in mediating these interactions. Complex formation was also detected when the two proteins were coexpressed in heterologous cells. In transfected cells, P0 and PMP22 are recruited and colocalize at the apposed plasma membranes of expressors as shown by confocal microscopy. These findings provide a new basis for a better understanding of myelin assembly and of the pathomechanisms involved in demyelinating peripheral neuropathies. Furthermore, these results propose a possible explanation why alterations in either of these molecules are sufficient to destabilize the myelin structure and cause a similar disease phenotype.

Inhibition of collagen IV deposition promotes regeneration of injured CNS axons.

Scarring impedes axon regrowth across the lesion site and is one major extrinsic constraint to effective regeneration in the adult mammalian central nervous system. In the present study we determined whether specific biochemical or immunochemical modulation of one major component of the scar, the basal membrane (BM), would provide a means to stimulate axon regeneration in the mechanically transected postcommissural fornix of the adult rat. Basal membrane developed within the first 2 weeks after transection in spatiotemporal coincidence with the abrupt growth arrest of spontaneously regrowing axons. Local injection of anticollagen IV antibodies or alpha, alpha'-dipyridyl, an inhibitor of collagen triple helix formation and synthesis, significantly reduced lesion-induced BM deposition. This treatment allowed massive axon elongation across the lesion site. Anterograde tracing provided unequivocal evidence that regenerating axons follow their original pathway, reinnervate the appropriate target, the mammillary body, and become remyelinated with compact myelin. Presynaptic electrophysiological recordings of regenerated fibre tracts showed recovery to nearly normal conduction properties. Our results indicate that lesion-induced BM is an impediment for successful axonal regeneration and its reduction is a prerequisite and sufficient condition for regrowing axons to cross the lesion site.

Focal ischaemia of the rat brain elicits an unusual inflammatory response: early appearance of CD8+ macrophages/microglia.

Cerebral ischaemia leads to profound glial activation and leukocyte infiltration into the infarct area. In this study, we provide evidence for a dual macrophage response in focal ischaemic lesions of the rat brain. We show that a considerable proportion of macrophages in the ischaemic lesions express the CD8alphabeta heterodimer to date only described on CD8+ T cells. As known from other lesion paradigms, CD4+ macrophages were also present. Interestingly, CD8- and CD4-expressing macrophages formed two non-overlapping subpopulations. CD8+ macrophages reached their maximum during the first week with pronounced downregulation thereafter whereas CD4+ cells persisted at high levels into the second week. In contrast to cerebral ischaemia, macrophages in the spleen and in Wallerian degeneration after optic nerve axotomy expressed CD4, but not CD8. In experimental autoimmune encephalomyelitis, CD8 was mainly associated with T cells and very weakly detectable on some ramified cells resembling activated microglia. In conclusion, we show that cerebral ischaemia triggers an unusual inflammatory response characterized by the appearance of CD8+/CD4- macrophages that might exert specific functions in the pathogenesis of ischaemic brain damage.