Stakeholders’ views on drug development: the congenital disorders of glycosylation community perspective

Background Congenital disorders of glycosylation (CDG) are a large family of rare genetic diseases for which therapies are virtually nonexistent. However, CDG therapeutic research has been expanding, thanks to the continuous efforts of the CDG medical/scientific and patient communities. Hence, CDG drug development is a popular research topic. The main aim of this study was to understand current and steer future CDG drug development and approval by collecting and analysing the views and experiences of the CDG community, encompassing professionals and families. An electronic (e-)survey was developed and distributed to achieve this goal. Results A total of 128 respondents (46 CDG professionals and 82 family members), mainly from Europe and the USA, participated in this study. Most professionals (95.0%) were relatively familiar with drug development and approval processes, while CDG families revealed low familiarity levels, with 8.5% admitting to never having heard about drug development. However, both stakeholder groups agreed that patients and families make significant contributions to drug development and approval. Regarding their perceptions of and experiences with specific drug development and approval tools, namely biobanks, disease models, patient registries, natural history studies (NHS) and clinical trials (CT), the CDG community stakeholders described low use and participation, as well as variable familiarity. Additionally, CDG professionals and families shared conflicting views about CT patient engagement and related information sharing. Families reported lower levels of involvement in CT design (25.0% declared ever being involved) and information (60.0% stated having been informed) compared to professionals (60.0% and 85.7%, respectively). These contrasting perceptions were further extended to their insights and experiences with patient-centric research. Finally, the CDG community (67.4% of professionals and 54.0% of families) reported a positive vision of artificial intelligence (AI) as a drug development tool. Nevertheless, despite the high AI awareness among CDG families (76.8%), professionals described limited AI use in their research (23.9%). Conclusions This community-centric study sheds new light on CDG drug development and approval. It identifies educational, communication and research gaps and opportunities for CDG professionals and families that could improve and accelerate CDG therapy development

Building the impedance model of a real machine

A reliable impedance model of a particle accelerator can be built by combining the beam coupling impedances of all the components. This is a necessary step to be able to evaluate the machine performance limitations, identify the main contributors in case an impedance reduction is required, and study the interaction with other mechanisms such as optics nonlinearities, transverse damper, noise, space charge, electron cloud, beam-beam (in a collider). The main phases to create a realistic impedance model, and verify it experimentally, will be reviewed, highlighting the main challenges. Some examples will be presented revealing the levels of precision of machine impedance models that have been achieved

Machine layout and performance

The Large Hadron Collider (LHC) is one of the largest scientific instruments ever built. Since opening up a new energy frontier for exploration in 2010, it has gathered a global user community of about 7,000 scientists working in fundamental particle physics and the physics of hadronic matter at extreme temperature and density. To sustain and extend its discovery potential, the LHC will need a major upgrade in the 2020s. This will increase its luminosity (rate of collisions) by a factor of five beyond the original design value and the integrated luminosity (total collisions created) by a factor ten. The LHC is already a highly complex and exquisitely optimised machine so this upgrade must be carefully conceived and will require about ten years to implement. The new configuration, known as High Luminosity LHC (HL-LHC), will rely on a number of key innovations that push accelerator technology beyond its present limits. Among these are cutting-edge 11-12 tesla superconducting magnets, compact superconducting cavities for beam rotation with ultra-precise phase control, new technology and physical processes for beam collimation and 300 metre-long high-power superconducting links with negligible energy dissipation. The present document describes the technologies and components that will be used to realise the project and is intended to serve as the basis for the detailed engineering design of HL-LHC

Testing Long-Range Beam-Beam Compensation for the LHC Luminosity Upgrade

The performance of the Large Hadron Collider (LHC) at CERN and its minimum crossing angle are limited by the effect of long-range beam-beam collisions. A wire compensators can mitigate part of the long-range effects and may allow for smaller crossing angles, or higher beam intensity. A prototype long-range wire compensator could be installed in the LHC by 2014/15. Since the originally reserved position for such a wire compensator is not available for this first step, we explore other possible options. Our investigations consider various longitudinal and transverse locations, different wire shapes, different optics configurations and several crossing angles between the two colliding beams. Simulations are carried out with the weak-strong code BBtrack. New postprocessing tools are introduced to analyse tune footprints and particle stability. In particular, a new method for the Lyapunov coefficient calculation is implemented. Submitted as "Tesi di laurea" at the University of Milano, 2012

Electromagnetic simulations for non-ultrarelativistic beams and applications to the CERN low energy machines

In the framework of the PS-Booster upgrade project an accurate impedance model is needed in order to determine the effect on the beam stability and assess the impact of the new devices to be installed in the machine. CST 3-D EM simulations are widely used to estimate the impedance contribution of the different devices along the CERN accelerator complex. Unlike the highly relativistic case, in which the reliability of the EM solver has been proved in many specific cases by comparing simulations with analytical results, the nonrelativistic case has been so far not yet benchmarked. In order to use systematically CST 3-D EM simulations for the PS-Booster, or even lower energy machines like the antiproton decelerator ELENA, a validation campaign has been carried out. The main complication to single out the beam coupling impedance, as resulting from the interaction of the beam with the surroundings, consisted of removing reliably the strong contribution of the direct space charge of the source bunch, which is included in the EM calculation. The simulation results were then benchmarked with the analytical results for the case of a PEC cylindrical tube and of a ferrite loaded kicker

LEIR impedance model and coherent beam instability observations

The LEIR machine is the first synchrotron in the ion ac-celeration chain at CERN and it is responsible to deliverhigh intensity ion beams to the LHC. Following the recentprogress in the understanding of the intensity limitations,detailed studies of the machine impedance started. In thiswork we describe the present LEIR impedance model, detail-ing the contribution to the total longitudinal and transverseimpedance of several machine elements. We then comparethe machine tune shift versus intensity predictions againstmeasurements at injection energy and summarize the co-herent instability observations in the absence of transversefeedback

Review of rest gas interaction at very low energies applied to the Extra Low Energy Antiproton ring ELENA

The Extremely Low ENergy Antiproton ring (ELENA) is a small synchrotron equipped with an electron cooler, which shall be constructed at CERN to decelerate antiprotons to energies as low as 100 keV. Scattering of beam particles on rest gas molecules may have a detrimental effect at such low energies and leads to stringent vacuum requirements. Within this contribution scattering of the stored beam on rest gas molecules is discussed for very low beam energies. It is important to carefully distinguish between antiprotons scattered out of the acceptance and lost, and those remaining inside the aperture to avoid overestimation of emittance blow-up. Furthermore, many antiprotons do not interact at all during the time they are stored in ELENA and hence this is not a multiple scattering proces

REVIEW OF REST GAS INTERACTION AT VERY LOW ENERGIES APPLIED TO THE EXTRA LOW ENERGY ANTIPROTON RING ELENA

Abstract The Extremely Low ENergy Antiproton ring (ELENA) is a small synchrotron equipped with an electron cooler, which shall be constructed at CERN to decelerate antiprotons to energies as low as 100 keV. Scattering of beam particles on rest gas molecules may have a detrimental effect at such low energies and leads to stringent vacuum requirements. Within this contribution scattering of the stored beam on rest gas molecules is discussed for very low beam energies. It is important to carefully distinguish between antiprotons scattered out of the acceptance and lost, and those remaining inside the aperture to avoid overestimation of emittance blow-up. Furthermore, many antiprotons do not interact at all during the time they are stored in ELENA and hence this is not a multiple scattering process

Chapter 2: Machine Layout and Performance

Chapter 2 in High-Luminosity Large Hadron Collider (HL-LHC) : Preliminary Design Report. The Large Hadron Collider (LHC) is one of the largest scientific instruments ever built. Since opening up a new energy frontier for exploration in 2010, it has gathered a global user community of about 7,000 scientists working in fundamental particle physics and the physics of hadronic matter at extreme temperature and density. To sustain and extend its discovery potential, the LHC will need a major upgrade in the 2020s. This will increase its luminosity (rate of collisions) by a factor of five beyond the original design value and the integrated luminosity (total collisions created) by a factor ten. The LHC is already a highly complex and exquisitely optimised machine so this upgrade must be carefully conceived and will require about ten years to implement. The new configuration, known as High Luminosity LHC (HL-LHC), will rely on a number of key innovations that push accelerator technology beyond its present limits. Among these are cutting-edge 11-12 tesla superconducting magnets, compact superconducting cavities for beam rotation with ultra-precise phase control, new technology and physical processes for beam collimation and 300 metre-long high-power superconducting links with negligible energy dissipation. The present document describes the technologies and components that will be used to realise the project and is intended to serve as the basis for the detailed engineering design of HL-LHC