Update on the safety and efficacy of teriparatide in the treatment of osteoporosis

Following the completion of the Fracture Prevention Trial, teriparatide was approved by the United States Food and Drug Administration and the European Medicine Agency as the first therapeutic anabolic agent for the treatment of postmenopausal women with severe osteoporosis. It subsequently received additional approval for the treatment of osteoporosis in men, and for the treatment of osteoporosis associated with glucocorticoid therapy in men and women at risk of fracture. In this review, we summarize the most important data concerning PTH 1-34 therapy before 2016 in the treatment of osteoporosis, and report some outstanding results published in the last 2 years. New data on safety will also discussed, together with the state of art of nonclassical utilization. Finally, in view of the recent approval of biosimilars, possible future landscapes are discussed

Development of non evaporable getter pumps for large hydrogen throughput and capacity in high vacuum regimes

In vacuum technology, capture pumps based on Non Evaporable Getters are commonly applied to ultra-high vacuum systems. Recent improvements in the absorption of hydrogenic species, with the introduction of Zr–V–Ti–Al alloys (ZAO®), make them an appealing and viable solution for the application in fusion research, and in particular for the vacuum system of neutral beam injectors (hydrogen pumping speed of thousands of m3/s, pressure of tens of mPa). This paper describes the characterization of the new NEG material in pumps of increasing dimensions, including the development, construction and test of a large mockup pump of modular design, to demonstrate the scalability of the technology. Effective pumping speeds of the order of 14 m3/s or higher at a concentration of 130 Pa m3/kg were achieved by the mockup pump, for an installed getter mass of about 16 kg, and a stability within 10% up to 1300 Pa m3/kg The measured effective pumping speed per unit area of sintered disks is of the order of 3.5 m/s, corresponding to 4.9 m/s at the disk surfaces as derived from numerical simulations. General guidelines for the design of large NEG pumps for hydrogen are discussed, including thermal aspects and duty cycle of the pump

Genetic aspects underlying the normocalcemic and hypercalcemic phenotypes of primary hyperparathyroidism

purpose: hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. we investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism. Research design and methods: Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral center. the data of both groups were compared with 54 in house-controls and 503 subjects from the 1,000 genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis. Results: The NPHPT group differed significantly at SNPs in OPG and ESR1. also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes. Conclusions: Our NPHPT patient set harboured a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies

Conceptual design of the DEMO neutral beam injectors: Main developments and R&D achievements

The objectives of the nuclear fusion power plant DEMO, to be built after the ITER experimental reactor, are usually understood to lie somewhere between those of ITER and a 'first of a kind' commercial plant. Hence, in DEMO the issues related to efficiency and RAMI (reliability, availability, maintainability and inspectability) are among the most important drivers for the design, as the cost of the electricity produced by this power plant will strongly depend on these aspects. In the framework of the EUROfusion Work Package Heating and Current Drive within the Power Plant Physics and Development activities, a conceptual design of the neutral beam injector (NBI) for the DEMO fusion reactor has been developed by Consorzio RFX in collaboration with other European research institutes. In order to improve efficiency and RAMI aspects, several innovative solutions have been introduced in comparison to the ITER NBI, mainly regarding the beam source, neutralizer and vacuum pumping systems

Start of SPIDER operation towards ITER neutral beams

Heating Neutral Beam (HNB) Injectors will constitute the main plasma heating and current drive tool both in ITER and JT60-SA, which are the next major experimental steps for demonstrating nuclear fusion as viable energy source. In ITER, in order to achieve the required thermonuclear fusion power gain Q=10 for short pulse operation and Q=5 for long pulse operation (up to 3600s), two HNB injectors will be needed [1], each delivering a total power of about 16.5 MW into the magnetically-confined plasma, by means of neutral hydrogen or deuterium particles having a specific energy of about 1 MeV. Since only negatively charged particles can be efficiently neutralized at such energy, the ITER HNB injectors [2] will be based on negative ions, generated by caesium-catalysed surface conversion of atoms in a radio-frequency driven plasma source. A negative deuterium ion current of more than 40 A will be extracted, accelerated and focused in a multi-aperture, multi-stage electrostatic accelerator, having 1280 apertures (~ 14 mm diam.) and 5 acceleration stages (~200 kV each) [3]. After passing through a narrow gas-cell neutralizer, the residual ions will be deflected and discarded, whereas the neutralized particles will continue their trajectory through a duct into the tokamak vessels to deliver the required heating power to the ITER plasma for a pulse duration of about 3600 s. Although the operating principles and the implementation of the most critical parts of the injector have been tested in different experiments, the ITER NBI requirements have never been simultaneously attained. In order to reduce the risks and to optimize the design and operating procedures of the HNB for ITER, a dedicated Neutral Beam Test Facility (NBTF) [4] has been promoted by the ITER Organization with the contribution of the European Union\u2019s Joint Undertaking for ITER and of the Italian Government, with the participation of the Japanese and Indian Domestic Agencies (JADA and INDA) and of several European laboratories, such as IPP-Garching, KIT-Karlsruhe, CCFE-Culham, CEA-Cadarache. The NBTF, nicknamed PRIMA, has been set up at Consorzio RFX in Padova, Italy [5]. The planned experiments will verify continuous HNB operation for one hour, under stringent requirements for beam divergence (< 7 mrad) and aiming (within 2 mrad). To study and optimise HNB performances, the NBTF includes two experiments: MITICA, full-scale NBI prototype with 1 MeV particle energy and SPIDER, with 100 keV particle energy and 40 A current, aiming at testing and optimizing the full-scale ion source. SPIDER will focus on source uniformity, negative ion current density and beam optics. In June 2018 the experimental operation of SPIDER has started

Progress in EU-DEMO in-vessel components integration

In the EU DEMO design (Romanelli, 2012; Federici et al., 2014), due to the large number of complex systems inside the tokamak vessel it is of vital importance to address the in-vessel integration at an early stage in the design process. In the EU DEMO design, after a first phase in which the different systems have been developed independently based on the defined baseline DEMO configuration, an effort has been made to define the interface requirements and to propose the strategies for the mechanical integration of the auxiliary heating and fuelling systems into the Vacuum Vessel and the Breeding Blanket. This work presents the options studied, the engineering solutions proposed, and the issues highlighted for the mechanical in-vessel integration of the DEMO fuelling lines, auxiliaries heating systems, and diagnostics

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

DTT - Divertor Tokamak Test facility: A testbed for DEMO

The effective treatment of the heat and power exhaust is a critical issue in the road map to the realization of the fusion energy. In order to provide possible, reliable, well assessed and on-time answers to DEMO, the Divertor Tokamak Test facility (DTT) has been conceived and projected to be carried out and operated within the European strategy in fusion technology. This paper, based on the invited plenary talk at the 31st virtual SOFT Conference 2020, provides an overview of the DTT scientific proposal, which is deeply illustrated in the 2019 DTT Interim Design Report