All Optical Implementation of Multi-Spin Entanglement in a Semiconductor Quantum Well

We use ultrafast optical pulses and coherent techniques to create spin entangled states of non-interacting electrons bound to donors (at least three) and at least two Mn2+ ions in a CdTe quantum well. Our method, relying on the exchange interaction between localized excitons and paramagnetic impurities, can in principle be applied to entangle a large number of spins.Comment: 17 pages, 3 figure

Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance

[EN] Background: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostatespecific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4¿5 mm). Results: The main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET. Conclusions: We have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organdedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.The work presented in this article has been partially funded by a research grant from the regional government of the Comunitat Valenciana (Spain), co-funded by the European Union ERDF funds (European Regional Development Fund) of the Comunitat Valenciana 2014-2020, with reference IDIFEDER/2018/032 (High-Performance Algorithms for the Modelling, Simulation and early Detection of diseases in Personalized Medicine). This project has also received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the EU Grant 603002 under the FP7 program and by the Spanish Ministerio de Economia, Industria y Competitividad under Grant e and through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad.Cañizares-Ledo, G.; Gonzalez-Montoro, A.; Freire, M.; Lamprou, E.; Barrio, J.; Sánchez Martínez, F.; Benlloch Baviera, JM.... (2020). Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance. EJNMMI Physics. 7(1):1-17. https://doi.org/10.1186/s40658-020-00305-yS11771GLOBOCAN 2018. http://www.gco.iarc.fr/today/ datasources-methods. Accessed 26 Dec 2019.Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN. Int J Cancer. 2012;2015:136–E359.Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10(2):63–89.Smith JA, et al. Transrectal ultrasound versus digital rectal examination for the staging of carcinoma of the prostate: results of a prospective multi-institutional trial. J Urology. 1997;157(3):902.Smeenge M, et al. Role of transrectal ultrasonography (TRUS) in focal therapy of prostate cancer: report from a consensus panel. BJU Int. 2012:110–942.Drost FJH, et al. Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer. Cochrane Database Syst Rev. 2019;4:CD012663.European Association of Urology. https://uroweb.org/guideline/prostate-cancer . Accessed 26 Dec 2019.Segall G, et al. SNM practice guideline for sodium 18F-fluoride PET/CT bone scans. J Nucl Med. 2010;51:1813.Yamamoto Y, et al. Feasibility of tailored, selective and effective anticancer chemotherapy by direct injection of docetaxel-loaded immunoliposomes into Her2/neu positive gastric tumor xenografts. Int J Oncol. 2011;38(1):33.Chen L, et al. MR-guided focused ultrasound: enhancement of intratumoral uptake of [H]-docetaxel in vivo. Phys Med Biol. 2010;55(24):–7399.Osborne JR, et al. Prostate-specific membrane antigen-based imaging. Seminars and Original Investigations: Urologic Oncology; 2012.Gonzalez AJ, et al. Organ-dedicated molecular imaging systems. IEEE Trans. Rad. Plasma Med. Scie. 2018;2:388.Majewski S, Proffitt J. Dedicated mobile high resolution prostate PET imager with an insertable transrectal probe. US Patent. 2010;7:858–944.Weinberg IN, et al. Flexible geometries for hand-held PET and SPECT cameras. IEEE NSS-MIC Conference Record. 2002.Weinberg I. Dedicated apparatus and method for positron emission tomography of the prostate. US Patent. 2006;7:102–34.Gonzalez-Montoro A, et al. Performance study of a large monolithic LYSO PET detector with accurate photon DOI using retroreflector layers. IEEE Trans. Rad. Plasma Med. Scie. 2017;1:229.Gonzalez-Montoro A, et al. Detector block performance based on a monolithic LYSO crystal using a novel signal multiplexing method. Nucl Instrum Meth. 2018;912:372-77.Gonzalez-Montoro A, et al. Performance comparison of large-area SiPM arrays suitable for gamma ray detectors. Biomed Phys Eng Express. 2019;5:045013.Seimetz M, et al. Correction algorithms for signal reduction in insensitive areas of a small gamma camera. J Instrum. 2014;9(05):C05042.Freire M, et al. Calibration of gamma ray impacts in monolithic-based detectors using Voronoi diagrams. In IEEE Transactions on Radiation and Plasma Medical Sciences. 2019. https://doi.org/10.1109/TRPMS.2019.2947716 .Jan S, et al. GATE: a simulation toolkit for PET and SPECT. Phys Med Biol. 2004;49:4543–61.Merlin T, et al. CASToR: a generic data organization and processing code framework for multi-modal and multi-dimensional tomographic reconstruction. Phys Med Biol. 2018;63(18):5505.Jacobs F, et al. A fast algorithm to calculate the exact radiological path through a pixel or voxel space. J Comput Inf Technol. 1998;6(1).Gonzalez-Montoro A, et al. Novel method to measure the intrinsic spatial resolution in PET detectors based on monolithic crystals. Nucl. Instrum. Meth. A. 2019;920:39(9).Vicente E, et al. Normalization in 3D PET: dependence on the activity distribution of the source. IEEE Nuclear Science Symposium Conference Record. 2006:M06–379.Soriano A, et al. Attenuation correction without transmission scan for the MAMMI breast PET. Nucl Instrum Meth A. 2011;648:S75.Yushkevich PA, et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. 2006;34(3):1116-28.Gonzalez AJ, et al. Initial results of the MINDView PET insert inside the 3T mMR. IEEE Trans Rad Plasma Med Scie. 2019;3:343.Suti S, et al. Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities. J Nucl Med. 2007;48(3):471–80.Watson C, et al. NEMA NU 2 performance tests for scanners with intrinsic radioactivity. J Nucl Med. 2004;45:822.National Electrical Manufacturers Association. NEMA NU 4-2008. Performance measurements of small animal positron emission tomographs. 2008.Gonzalez AJ, et al. A PET design based on SiPM and monolithic LYSO crystals: performance evaluation. IEEE Trans Nucl Scie. 2016;63:2471.Barbosa FG. Clinical perspectives of PSMA PET/MRI for prostate cancer. Clinics. 2018;73(Suppl 1):e586s.Uprimny C, et al. (68)Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44(6):941-49.Koerber SA, et al. 68Ga-PSMA-11 PET/CT in newly diagnosed carcinoma of the prostate: correlation of intraprostatic PSMA uptake with several clinical parameters. J Nucl Med. 2017;58(12):1943–8

Combinatorial experimental protocols for Erbicin-derived immunoagents and Herceptin

Erbicin is a human anti-ErbB2 single-chain antibody fragment with high affinity and selectivity for ErbB2-positive cancer cells. Two anti-ErbB2 immunoconjugates, called Erb-hRNase and Erb-hcAb, have been prepared and found to be selectively cytotoxic on ErbB2-positive cancer cells in vitro and vivo. In Erb-hRNase, Erbicin is linked to a human RNase and in Erb-hcAb it is linked to the key structural and functional regions of a human IgG. Herceptin is an anti-ErbB2 humanised antibody successfully used in the immunotherapy of breast cancer. We report here that the Erbicin-derived immunoagents target on breast cancer cells an ErbB2 epitope different than that of Herceptin. This finding led us to verify the effects of Herceptin on breast cancer cells when it was used in combination with the Erbicin-derived immunoagents. The results indicated that in combination experiments the antitumour action of Herceptin and that of the novel agents were significantly increased in an additive fashion. An inspection of the mechanism of action of Erb-hRNase or Erb-hcAb combined with Herceptin provided evidence that the antibody combinations engendered an increased downregulation of the ErbB2 receptor, and led to an enhanced apoptotic cell death

Quality control and beam test of GEM detectors for future upgrades of the CMS muon high rate region at the LHC

Gas Electron Multipliers (GEM) are a proven position sensitive gas detector technology which nowadays is becoming more widely used in High Energy Physics. GEMs offer an excellent spatial resolution and a high particle rate capability, with a close to 100% detection efficiency. In view of the high luminosity phase of the CERN Large Hadron Collider, these aforementioned features make GEMs suitable candidates for the future upgrades of the Compact Muon Solenoid (CMS) detector. In particular, the CMS GEM Collaboration proposes to cover the high-eta region of the muon system with large-area triple-GEM detectors, which have the ability to provide robust and redundant tracking and triggering functions. In this contribution, after a general introduction and overview of the project, the construction of full-size trapezoidal triple-GEM prototypes will be described in more detail. The procedures for the quality control of the GEM foils, including gain uniformity measurements with an x-ray source will be presented. In the past few years, several CMS triple-GEM prototype detectors were operated with test beams at the CERN SPS. The results of these test beam campaigns will be summarised

Bethe-hole polarization analyser for the magnetic vector of light

The nature of light as an electromagnetic wave with transverse components has been confirmed using optical polarizers, which are sensitive to the orientation of the electric field. Recent advances in nanoscale optical technologies demand their magnetic counterpart, which can sense the orientation of the optical magnetic field. Here we report that subwavelength metallic apertures on infinite plane predominantly sense the magnetic field of light, establishing the orientation of the magnetic component of light as a separate entity from its electric counterpart. A subwavelength aperture combined with a tapered optical fibre probe can also serve as a nanoscale polarization analyser for the optical magnetic field, analogous to a nanoparticle sensing the local electric polarization. As proof of its functionality, we demonstrate the measurement of a magnetic field orientation that is parallel to the electric field, as well as a circularly polarized magnetic field in the presence of a linearly polarized electric field

Phase I Study of Safety and Immunogenicity of an Escherichia coli-Derived Recombinant Protective Antigen (rPA) Vaccine to Prevent Anthrax in Adults

The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA).A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA.The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses.ClinicalTrials.gov NCT00057525

A “reverse pharmacology” approach for developing an anti-malarial phytomedicine

A “reverse pharmacology” approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of “reverse pharmacology” shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered

"Test and treat" or presumptive treatment for malaria in high transmission situations? A reflection on the latest WHO guidelines

Recent WHO guidelines recommend a universal "test and treat" strategy for malaria, mainly by use of rapid diagnostic test (RDT) in all areas. The evidence for this approach is questioned here as there is a risk of over-reliance on parasitological diagnosis in high transmission situations, which still exist. In such areas, when a patient has fever or other malaria symptoms, the presence of Plasmodium spp neither reliably confirms malaria as the cause of the fever, nor excludes the possibility of other diseases. This is because the patient may be an asymptomatic carrier of malaria parasites and suffer from another disease

Relatively Low HIV Infection Rates in Rural Uganda, but with High Potential for a Rise: A Cohort Study in Kayunga District, Uganda

BACKGROUND: Few studies have been conducted in Uganda to identify and quantify the determinants of HIV-1 infection. We report results from a community-based cohort study, whose primary objectives were to determine HIV-1 prevalence, incidence, and determinants of these infections, among other objectives. METHODOLOGY: Consenting volunteers from the rural district of Kayunga in Uganda aged 15-49 years were enrolled between March and July 2006. Participants were evaluated every six months. A questionnaire that collected information on behavioral and other HIV-1 risk factors was administered, and a blood sample obtained for laboratory analysis at each study visit. PRINCIPAL FINDINGS: HIV-1 prevalence among the 2025 participants was 9.9% (95% CI = 8.6%-11.2%). By the end of 12 months of follow-up, 1689.7 person-years had been accumulated, with a median follow-up time of 11.97 months. Thirteen HIV-1 incident cases were detected giving an annual HIV-1 incidence of 0.77% (95% CI = 0.35-1.19). Prevalence of HSV-2 infection was 57% and was strongly associated with prevalent HIV-1 infection (adjusted Odds Ratio = 3.9, 95% CI = 2.50-6.17); as well as incident HIV-1 infection (adjusted Rate Ratio (RR) = 8.7, 95% CI = 1.11-67.2). The single most important behavioral characteristic associated with incident HIV infection was the number of times in the past 6 months, a participant had sex with person(s) they suspected/knew were having sex with others; attaining statistical significance at 10 times and higher (adjusted RR = 6.3, 95% CI = 1.73-23.1). By the end of 12 months of follow-up, 259 participants (13%) were lost to follow-up, 13 (0.6%) had died, and 2 (0.1%) had withdrawn consent. CONCLUSIONS: Despite relatively low HIV-1 incidence observed in this community, prevalence remains relatively high. In the presence of high prevalence of HSV-2 infection and the behavioral characteristic of having sex with more than one partner, there is potential for increase in HIV-1 incidence

Crack formation and prevention in colloidal drops

Crack formation is a frequent result of residual stress release from colloidal films made by the evaporation of colloidal droplets containing nanoparticles. Crack prevention is a significant task in industrial applications such as painting and inkjet printing with colloidal nanoparticles. Here, we illustrate how colloidal drops evaporate and how crack generation is dependent on the particle size and initial volume fraction, through direct visualization of the individual colloids with confocal laser microscopy. To prevent crack formation, we suggest use of a versatile method to control the colloid-polymer interactions by mixing a nonadsorbing polymer with the colloidal suspension, which is known to drive gelation of the particles with short-range attraction. Gelation-driven crack prevention is a feasible and simple method to obtain crack-free, uniform coatings through drying-mediated assembly of colloidal nanoparticlesopen0