Design and advancement status of the Beam Expander Testing X-ray facility (BEaTriX)

The BEaTriX (Beam Expander Testing X-ray facility) project is an X-ray apparatus under construction at INAF/OAB to generate a broad (200 x 60 mm2), uniform and low-divergent X-ray beam within a small lab (6 x 15 m2). BEaTriX will consist of an X-ray source in the focus a grazing incidence paraboloidal mirror to obtain a parallel beam, followed by a crystal monochromation system and by an asymmetrically-cut diffracting crystal to perform the beam expansion to the desired size. Once completed, BEaTriX will be used to directly perform the quality control of focusing modules of large X-ray optics such as those for the ATHENA X-ray observatory, based on either Silicon Pore Optics (baseline) or Slumped Glass Optics (alternative), and will thereby enable a direct quality control of angular resolution and effective area on a number of mirror modules in a short time, in full X-ray illumination and without being affected by the finite distance of the X-ray source. However, since the individual mirror modules for ATHENA will have an optical quality of 3-4 arcsec HEW or better, BEaTriX is required to produce a broad beam with divergence below 1-2 arcsec, and sufficient flux to quickly characterize the PSF of the module without being significantly affected by statistical uncertainties. Therefore, the optical components of BEaTriX have to be selected and/or manufactured with excellent optical properties in order to guarantee the final performance of the system. In this paper we report the final design of the facility and a detailed performance simulation.Comment: Accepted paper, pre-print version. The finally published manuscript can be downloaded from http://dx.doi.org/10.1117/12.223895

Simbol-X Hard X-ray Focusing Mirrors: Results Obtained During the Phase A Study

Simbol-X will push grazing incidence imaging up to 80 keV, providing a strong improvement both in sensitivity and angular resolution compared to all instruments that have operated so far above 10 keV. The superb hard X-ray imaging capability will be guaranteed by a mirror module of 100 electroformed Nickel shells with a multilayer reflecting coating. Here we will describe the technogical development and solutions adopted for the fabrication of the mirror module, that must guarantee an Half Energy Width (HEW) better than 20 arcsec from 0.5 up to 30 keV and a goal of 40 arcsec at 60 keV. During the phase A, terminated at the end of 2008, we have developed three engineering models with two, two and three shells, respectively. The most critical aspects in the development of the Simbol-X mirrors are i) the production of the 100 mandrels with very good surface quality within the timeline of the mission; ii) the replication of shells that must be very thin (a factor of 2 thinner than those of XMM-Newton) and still have very good image quality up to 80 keV; iii) the development of an integration process that allows us to integrate these very thin mirrors maintaining their intrinsic good image quality. The Phase A study has shown that we can fabricate the mandrels with the needed quality and that we have developed a valid integration process. The shells that we have produced so far have a quite good image quality, e.g. HEW <~30 arcsec at 30 keV, and effective area. However, we still need to make some improvements to reach the requirements. We will briefly present these results and discuss the possible improvements that we will investigate during phase B.Comment: 6 pages, 3 figures, invited talk at the conference "2nd International Simbol-X Symposium", Paris, 2-5 december, 200

Digitalization and co-creation of healthcare value: A case study in Occupational Health

This paper discusses how digitalization of healthcare empowers stakeholders to interact and co-create value. The literature so far has focused on the benefits of healthcare value co-creation through digital technologies (DTs) from the patients and providers’ perspective. It has viewed patients and providers in isolation focusing on the benefits accruing to the healthcare system but has not shed light upon the role of DT during interactions between stakeholders to co-create healthcare value. To address this gap, this research uses a case of the ‘Occupational Health Adviceline’ (OHA), a DT-enabled Occupational Health (OH) service introduced in England to provide support and advice to Small and Medium Enterprises (SMEs). We draw upon the affordances and S-D Logic concepts to illustrate how technology enables stakeholder (employees, employers, contact centre advisors, and OH nurses) empowerment and allows them to interact and co-create healthcare value. Our contribution lies in illustrating, through the affordances and S-D Logic lenses, how digitalization facilitates value co-creation through empowering stakeholders while providing new forms of visibility management.British Academy / Leverhulme Trust (grant no. SG122331); Knowledge Transfer Leave (Brunel University London)

Physical Investigation of the Potentially Hazardous Asteroid (144898) 2004 VD17

In this paper we present the observational campaign carried out at ESO NTT and VLT in April and May 2006 to investigate the nature and the structure of the Near Earth Object (144898) 2004 VD17. In spite of a great quantity of dynamical information, according to which it will have a close approach with the Earth in the next century, the physical properties of this asteroid are largely unknown. We performed visible and near--infrared photometry and spectroscopy, as well as polarimetric observations. Polarimetric and spectroscopic data allowed us to classify 2004 VD17 as an E-type asteroid. A good agreement was also found with the spectrum of the aubrite meteorite Mayo Belwa. On the basis of the polarimetric albedo (p_v=0.45) and of photometric data, we estimated a diameter of about 320 m and a rotational period of about 2 hours. The analysis of the results obtained by our complete survey have shown that (144898) 2004 VD17 is a peculiar NEO, since it is close to the breakup limits for fast rotator asteroids, as defined by Pravec and Harris (2000). These results suggest that a more robust structure must be expected, as a fractured monolith or a rubble pile in a "strength regime" (Holsapple 2002).Comment: 32 pages, 7 figure, paper accepted for publication in Icaru

Novel bicistronic lentiviral vectors correct beta-Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis

The favorable outcome of in vivo and ex vivo gene therapy approaches in several Lysosomal Storage Diseases suggests that these treatment strategies might equally benefit GM2 gangliosidosis. Tay-Sachs and Sandhoff disease (the main forms of GM2 gangliosidosis) result from mutations in either the HEXA or HERB genes encoding, respectively, the alpha- or beta-subunits of the lysosomal beta-Hexosaminidase enzyme. In physiological conditions, alpha- and beta-subunits combine to generate beta-Hexosaminidase A (HexA, alpha beta) and beta-Hexosaminidase B (HexB, 1313). A major impairment to establishing in vivo or ex vivo gene therapy for GM2 gangliosidosis is the need to synthesize the alpha- and beta-subunits at high levels and with the correct stoichiometric ratio, and to safely deliver the therapeutic products to all affected tissues/organs. Here, we report the generation and in vitro validation of novel bicistronic lentiviral vectors (LVs) encoding for both the murine and human codon optimized Hexa and Hex!) genes. We show that these LVs drive the safe and coordinate expression of the alpha- and beta-subunits, leading to supranormal levels of beta-Hexosaminidase activity with prevalent formation of a functional HexA in SD murine neurons and glia, murine bone marrow-derived hematopoietic stem/progenitor cells (HSPCs), and human SD fibroblasts. The restoration/overexpression of beta-Hexosaminidase leads to the reduction of intracellular GM2 ganglioside storage in transduced and in cross-corrected SD murine neural progeny, indicating that the transgenic enzyme is secreted and functional. Importantly, bicistronic LVs safely and efficiently transduce human neurons/glia and CD34 + HSPCs, which are target and effector cells, respectively, in prospective in vivo and ex vivo GT approaches. We anticipate that these bicistronic LVs may overcome the current requirement of two vectors co-delivering the alpha- or beta-subunits genes. Careful assessment of the safety and therapeutic potential of these bicistronic LVs in the SD murine model will pave the way to the clinical development of LV-based gene therapy for GM2 gangliosidosis

Identifying Near Earth Object Families

The study of asteroid families has provided tremendous insight into the forces that sculpted the main belt and continue to drive the collisional and dynamical evolution of asteroids. The identification of asteroid families within the NEO population could provide a similar boon to studies of their formation and interiors. In this study we examine the purported identification of NEO families by Drummond (2000) and conclude that it is unlikely that they are anything more than random fluctuations in the distribution of NEO osculating orbital elements. We arrive at this conclusion after examining the expected formation rate of NEO families, the identification of NEO groups in synthetic populations that contain no genetically related NEOs, the orbital evolution of the largest association identified by Drummond (2000), and the decoherence of synthetic NEO families intended to reproduce the observed members of the same association. These studies allowed us to identify a new criterion that can be used to select real NEO families for further study in future analyses, based on the ratio of the number of pairs and the size of strings to the number of objects in an identified association.Comment: Accepted for publication in Icarus. 19 pages including 11 figure

Acute kidney injury and acute kidney disease in high-dose cisplatin-treated head and neck cancer

Background: In locally advanced head and neck squamous cell carcinoma (LA-SCCHN) at least 200mg/m2 (standard dose 300 mg/m2) of cisplatin concomitant with radiotherapy represents the standard of care, both in postoperative and conservative settings. Nevertheless, high dose administration every 3 weeks is often replaced with low dose weekly cisplatin to avoid toxicities like kidney injury, though often failing to reach the therapeutic dose. Our aim was to investigate the incidence of renal impairment in the real-life setting, integrating high dose cisplatin with adequate supportive therapy, and to explore both Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD), a recently described clinical renal syndrome that encompasses functional alterations of the kidney lasting fewer than 3 months. Methods: One hundred and nine consecutive patients affected by LA-SCCHN and treated with at least a cumulative dosage of 200 mg/m2 of cisplatin concomitant with radiotherapy were enrolled in this prospective observational study. Results: AKI was reported in 12.8% of patients, 50% of whom were stage 1 (KDIGO criteria), while 25.7% of the cohort developed AKD. Patients with baseline estimated Glomerular Filtration Rate (eGFR) &lt; 90 ml/min showed a higher incidence of AKD (36.2% vs 17.7%). Hypertension, baseline eGFR, and therapy with Renin-angiotensin-aldosterone system inhibitors proved to be significant factors associated with both AKI and AKD. Conclusion: AKI and AKD are not rare complications of high-dose cisplatin, but an appropriate prevention strategy and accurate monitoring of patients during treatment could lead to a reduction of the burden of these conditions

Evaluation of a New, Rapid, Fully Automated Assay for the Measurement of ADAMTS13 Activity

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (&lt; 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. A method comparison study was performed on 176 samples from 49 healthy donors and 127 TMA patients (109 TTP, 7 atypical hemolytic uremic syndrome, 11 other TMAs), comparing this new assay with an in-house FRETS-VWF73 assay and a commercial enzyme-linked immunosorbent assay (ELISA) (TECHNOZYM ADAMTS-13 Activity, Technoclone GmbH, Vienna, Austria). Agreement between methods was assessed with focus on ADAMTS13 activity less than 10%, the medical decision level relevant for TTP diagnosis. The HemosIL AcuStar ADAMTS13 Activity showed good correlation with both the FRETS-VWF73 (r = 0.96) and ELISA (r = 0.96) methods. Slope of the Passing-Bablok regression was 1.05 for FRETS-VWF73 and 1.02 for ELISA, and absolute bias at the medical decision level was +0.1 and +0.3%, respectively. The study also revealed high agreement with FRETS-VWF73 (kappa 0.97) and ELISA (kappa 0.98) methods in classifying TTP patients with a severe deficiency of ADAMTS13 activity. Because of its short turnaround time and full automation, the HemosIL AcuStar ADAMTS13 activity assay might become the assay of choice to rapidly test ADAMTS13 activity in plasma and thus establish the diagnosis of acute TTP in emergency settings