Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin ...amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.
Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to ...organ damage and death. For other late-onset fatal diseases, as Huntington's disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients' characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.
In 2004, Ohtomo and Hwang discovered that an electron gas is created at the interface between insulating LaAlO3 and SrTiO3 compounds. Here we show that the generation of a conducting electron gas is ...related to an orbital reconstruction occurring at the LaAlO3/SrTiO3 interface. Our results are based on extensive investigations of the electronic properties and of the orbital structure of the interface using x-ray absorption spectroscopy. In particular, we find that the degeneracy of the Ti 3d states is fully removed and that the Ti 3d xy levels become the first available states for conducting electrons.
Studies of silicon photomultipliers at cryogenic temperatures Collazuol, G.; Bisogni, M.G.; Marcatili, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2011, Letnik:
628, Številka:
1
Journal Article
Recenzirano
We investigate the behavior of silicon photomultipliers (SiPMs) at low temperatures:
I–
V characteristics, breakdown voltage, dark noise, afterpulsing, crosstalk, pulse shape, gain and photon ...detection efficiency are studied as a function of temperature in the range
50
K
<
T
<
320
K
. We discuss our measurements on the basis of the temperature dependent properties of silicon and of the models related to carrier generation, transport and multiplication in high electric field. We conclude that SiPMs provide an excellent alternative to vacuum tube photomultipliers (PMTs) in low temperature environments, even better than in room temperature ones: in particular they excel in the interval
100
K
<
T
<
200
K
.
We probe the collective magnetic modes of La2CuO4 and underdoped La2-xSrxCuO4 (LSCO) by momentum resolved resonant inelastic x-ray scattering (RIXS) at the Cu L3 edge. For the undoped ...antiferromagnetic sample, we show that the single magnon dispersion measured with RIXS coincides with the one determined by inelastic neutron scattering, thus demonstrating that x rays are an alternative to neutrons in this field. In the spin dynamics of LSCO, we find a branch dispersing up to approximately 400 meV coexisting with one at lower energy. The high-energy branch has never been seen before. It indicates that underdoped LSCO is in a dynamic inhomogeneous spin state.
Positron emission tomography is one of the most mature techniques for monitoring the particles range in hadron therapy, aiming to reduce treatment uncertainties and therefore the extent of safety ...margins in the treatment plan. In-beam PET monitoring has been already performed using inter-spill and post-irradiation data, i.e. while the particle beam is off or paused. The full beam acquisition procedure is commonly discarded because the particle spills abruptly increase the random coincidence rates and therefore the image noise. This is because random coincidences cannot be separated by annihilation photons originating from radioactive decays and cannot be corrected with standard random coincidence techniques due to the time correlation of the beam-induced background with the ion beam microstructure. The aim of this paper is to provide a new method to recover in-spill data to improve the images obtained with full-beam PET acquisitions. This is done by estimating the temporal microstructure of the beam and thus selecting input PET events that are less likely to be random ones. The PET detector we used was the one developed within the INSIDE project and tested at the CNAO synchrotron-based facility. The data were taken on a PMMA phantom irradiated with 72 MeV proton pencil beams. The obtained results confirm the possibility of improving the acquired PET data without any external signal coming from the synchrotron or ad hoc detectors.
Positron emission tomography (PET) is one of the most mature techniques for monitoring in ion beam therapy. PET allows to reconstruct the β+ activity generated in the patient by the nuclear ...interaction of the ions. Taking advantage of the spatial correlation between positron emitters created along the ions path and the dose distribution, it is possible to perform a quality control of the treatment. Usually, to reconstruct the activity generated within the irradiated volume, standard 3D PET reconstruction techniques are implemented. In this work, we explore a new reconstruction method (Straight Forward Reconstruction) particularly useful for reconstructing activity distribution generated by mono-energetic pencil beams. The method was validated by measuring the produced activity distribution with the DoPET system. Irradiations performed with mono-energetic pencil beams on phantoms mimicking human tissues were used for this study. Both reconstruction methods reach an accuracy in the reconstruction of the activity distribution width of the order of 1.5 mm for 2⋅108 primaries.
•PET is one of the most mature techniques for monitoring in ion beam therapy.•A new reconstruction method (Straight Forward Reconstruction) for PET is presented.•Activity distribution and accuracy by pencil beams irradiation are presented.
This paper reports the development of dosimeters based on plastic scintillating fibers imaged by a charge-coupled device camera, and their performance evaluation through irradiations with the ...electron Flash research accelerator located at the Centro Pisano Flash Radiotherapy. The dosimeter prototypes were composed of a piece of plastic scintillating fiber optically coupled to a clear optical fiber which transported the scintillation signal to the readout systems (an imaging system and a photodiode). The following properties were tested: linearity, capability to reconstruct the percentage depth dose curve in solid water and to sample in time the single beam pulse. The stem effect contribution was evaluated with three methods, and a proof-of-concept one-dimensional array was developed and tested for online beam profiling. Results show linearity up to 10 Gy per pulse, and good capability to reconstruct both the timing and spatial profiles of the beam, thus suggesting that plastic scintillating fibers may be good candidates for low-energy electron Flash dosimetry.
•Flash radiotherapy may be groundbreaking for improving cancer treatment.•Conventional dosimeters do not function properly in the Flash regime.•Dosimeters based on plastic scintillating fibers were developed and characterized.•No quenching or energy dependence was observed in the Flash regime.•The beam time structure could be properly sampled.
By resonant inelastic x-ray scattering in the soft x-ray regime we probe the dynamical multiple-spin correlations in the antiferromagnetic cuprates La2CuO4 and CaCuO2. High resolution measurements at ...the copper L3 edge allow the clear observation of dispersing bimagnon excitations. Theory based on the ultrashort core-hole lifetime expansion fits the data on these coherent spin excitations without free parameters.
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