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Energy-recovery linacs (ERLs) have been emphasised by the recent (2020) update of the European Strategy for Particle Physics as one of the most promising technologies for the accelerator base of future high-energy physics. The current paper has been written as a base document to support and specify details of the recently published European roadmap for the development of energy-recovery linacs. The paper summarises the previous achievements on ERLs and the status of the field and its basic technology items. The main possible future contributions and applications of ERLs to particle and nuclear physics as well as industrial developments are presented. The paper includes a vision for the further future, beyond 2030, as well as a comparative data base for the main existing and forthcoming ERL facilities. A series of continuous innovations, such as on intense electron sources or high-quality superconducting cavity technology, will massively contribute to the development of accelerator physics at large. Industrial applications are potentially revolutionary and may carry the development of ERLs much further, establishing another shining example of the impact of particle physics on society and its technical foundation with a special view on sustaining nature.

I watched as that decision ran into more and more opposition and then, finally, on the evening before the decision was made not to dump, I was asked to manage the retreat, and spent the next three weeks leading a handpicked team of people inside Shell to pick our way through how to get out of the mess we'd got ourselves into. There was tremendous work done to make sure the retreat didn't turn into a row. We couldn't carry the great mass of people in the organisation, we couldn't carry them overseas and we had no sensible argument to counter stheir view that this was like throwing a Coca- Cola can in a local pond. Our explanation that it was like dumping a needle in Loch Ness didn't capture the hearts and minds of the public who were affected.

Excited levels were attributed to \\(^{81}_{31}\\)Ga\\(_{50}\\) for the first time which were fed in the \\(\\beta\\)-decay of its mother nucleus \\(^{81}\\)Zn produced in the fission of \\(^{nat}\\)U using the ISOL technique. We show that the structure of this nucleus is consistent with that of the less exotic proton-deficient N=50 isotones within the assumption of strong proton Z=28 and neutron N=50 effective shell effects.

gamma-rays following the B and B-n decay of the very neutron rich 84Ga produced by photo-fission of 238U have been studied at the newly built ISOL facility of IPN Orsay: ALTO. Two activities were observed and assigned to two B-decaying states: 84gGa, I = (0\\^-) and 84mGa, I = (3\\^-, 4\\^-). Excitation energies of the 2+1 and 4+1 excited states of 84Ge were measured at E(2+1) = 624.3 keV and E(4+1) = 1670.1 keV. Comparison with HFB+GCM calculations allows to establish the collective character of this nucleus indicating a substantial N=50 core polarization. The excitation energy of the 1/2+1 state in 83Ga known to carry a large part of the neutron 3s1/2 strength was measured at 247.8keV. Altogether these data allow to confirm the new single particle state ordering which appears immediately after the double Z=28 and N=50 shell closure and to designate 78Ni as a fragile and easily polarized doubly-magic core.

Background American Indian elders, aged 55 years and older, represent a neglected segment of the United States (U.S.) health care system. This group is more likely to be uninsured and to suffer from greater morbidities, poorer health outcomes and quality of life, and lower life expectancies compared to all other aging populations in the country. Despite the U.S. government’s federal trust responsibility to meet American Indians’ health-related needs through the Indian Health Service (IHS), elders are negatively affected by provider shortages, limited availability of health care services, and gaps in insurance. This qualitative study examines the perspectives of professional stakeholders involved in planning, delivery of, and advocating for services for this population to identify and analyze macro- and meso-level factors affecting access to and use of health care and insurance among American Indian elders at the micro level. Methods Between June 2016 and March 2017, we undertook in-depth qualitative interviews with 47 professional stakeholders in two states in the Southwest U.S., including health care providers, outreach workers, public-sector administrators, and tribal leaders. The interviews focused on perceptions of both policy- and practice-related factors that bear upon health care inequities impacting elders. We analyzed iteratively the interview transcripts, using both open and focused coding techniques, followed by a critical review of the findings by a Community Action Board comprising American Indian elders. Results Findings illuminated complex and multilevel contextual influences on health care inequities for elders, centering on (1) gaps in elder-oriented services; (2) benefits and limits of the Affordable Care Act (ACA); (2) invisibility of elders in national, state, and tribal policymaking; and (4) perceived threats to the IHS system and the federal trust responsibility. Conclusions Findings point to recommendations to improve the prevention and treatment of illness among American Indian elders by meeting their unique health care and insurance needs. Policies and practices must target meso and macro levels of contextual influence. Although Medicaid expansion under the ACA enables providers of essential services to elders, including the IHS, to enhance care through increased reimbursements, future policy efforts must improve upon this funding situation and fulfill the federal trust responsibility.

HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI), a major receptor of high-density lipoprotein (HDL), the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

Background Public insurance reforms of the past two decades have failed to substantively address the healthcare needs of American Indians in general, let alone the particular needs of American Indian elders, ages 55 years and older. Historically, this population is more likely to be uninsured and to suffer from greater morbidities, poorer health outcomes and quality of life, and lower life expectancies compared to all other United States aging populations, representing a neglected group within the healthcare system. Despite the pervasive belief that the Indian Health Service will address all their health-related needs, American Indian elders are negatively affected by gaps in insurance and lack of access to health care. While the 2010 Patient Protection and Affordable Care Act included provisions to ameliorate disparities for American Indians, its future is uncertain. In this context, American Indian elders with variable health literacy must navigate a complex and unstable healthcare system, regardless of where they seek care. Methods This community-driven study features a mixed-method, participatory design to examine help-seeking behavior and healthcare experiences of American Indian elders in New Mexico, in order to develop and evaluate a tailored intervention to enhance knowledge of, access to, and use of insurance and available services to reduce healthcare disparities. This study includes qualitative and quantitative interviews combined with concept mapping and focus groups with American Indian elders and other key stakeholders. Discussion The information gathered will generate new practical knowledge, grounded in actual perspectives of American Indian elders and other relevant stakeholders, to improve healthcare practices and policies for a population that has been largely excluded from national and state discussions of healthcare reform. Study data will inform development and evaluation of culturally tailored programming to enhance understanding and facilitate negotiation of the changing landscape of health care by American Indian elders. This work will fill a gap in research on public insurance initiatives, which do not typically focus on this population, and will offer a replicable model for enhancing the effects of such initiatives on other underserved groups affected by healthcare inequities. Trial registration This protocol does not include the collection of health outcome data. Clinicaltrials.gov, NCT03550404 . Registered June 6, 2018.

Approximately 20% of traumatic cervical spinal cord injuries result in tetraplegia. Neuroprosthetics are being developed to manage this condition and thus improve the lives of patients. We aimed to test the feasibility of a semi-invasive technique that uses brain signals to drive an exoskeleton. We recruited two participants at Clinatec research centre, associated with Grenoble University Hospital, Grenoble, France, into our ongoing clinical trial. Inclusion criteria were age 18–45 years, stability of neurological deficits, a need for additional mobility expressed by the patient, ambulatory or hospitalised monitoring, registration in the French social security system, and signed informed consent. The exclusion criteria were previous brain surgery, anticoagulant treatments, neuropsychological sequelae, depression, substance dependence or misuse, and contraindications to magnetoencephalography (MEG), EEG, or MRI. One participant was excluded because of a technical problem with the implants. The remaining participant was a 28-year-old man, who had tetraplegia following a C4–C5 spinal cord injury. Two bilateral wireless epidural recorders, each with 64 electrodes, were implanted over the upper limb sensorimotor areas of the brain. Epidural electrocorticographic (ECoG) signals were processed online by an adaptive decoding algorithm to send commands to effectors (virtual avatar or exoskeleton). Throughout the 24 months of the study, the patient did various mental tasks to progressively increase the number of degrees of freedom. Between June 12, 2017, and July 21, 2019, the patient cortically controlled a programme that simulated walking and made bimanual, multi-joint, upper-limb movements with eight degrees of freedom during various reach-and-touch tasks and wrist rotations, using a virtual avatar at home (64·0% [SD 5·1] success) or an exoskeleton in the laboratory (70·9% [11·6] success). Compared with microelectrodes, epidural ECoG is semi-invasive and has similar efficiency. The decoding models were reusable for up to approximately 7 weeks without recalibration. These results showed long-term (24-month) activation of a four-limb neuroprosthetic exoskeleton by a complete brain–machine interface system using continuous, online epidural ECoG to decode brain activity in a tetraplegic patient. Up to eight degrees of freedom could be simultaneously controlled using a unique model, which was reusable without recalibration for up to about 7 weeks. French Atomic Energy Commission, French Ministry of Health, Edmond J Safra Philanthropic Foundation, Fondation Motrice, Fondation Nanosciences, Institut Carnot, Fonds de Dotation Clinatec.

Rationale. The optimal strategy for initiation of renal replacement therapy (RRT) in patients with severe acute kidney injury in the context of septic shock and acute respiratory distress syndrome (ARDS) is unknown. Objectives: To examine the effect of an early compared with a delayed RRT initiation strategy on 60 day mortality according to baseline sepsis status, ARDS status, and severity. Methods: Post hoc analysis of the AKIKI (Artificial Kidney Initiation in Kidney Injury) trial. Measurements and Main Results: Subgroups were defined according to baseline characteristics: sepsis status (Sepsis-3 definition), ARDS status (Berlin definition), Simplified Acute Physiology Score 3 (SAPS 3), and Sepsis-related Organ Failure Assessment (SOFA). Of 619 patients, 348 (56%) had septic shock, and 207 (33%) had ARDS. We found no significant influence of the baseline sepsis status (P = 0.28), baseline ARDS status (P = 0.94), and baseline severity scores (P = 0.77 and P = 0.46 for SAPS 3 and SOFA, respectively) on the comparison of 60-day mortality according to RRT initiation strategy. A delayed RRT initiation strategy allowed 45% of patients with septic shock and 46% of patients with ARDS to escape RRT. Urine output was higher in the delayed group. Renal function recovery occurred earlier with the delayed RRT strategy in patients with septic shock or ARDS (P <0.001 and P = 0.003, respectively). Time to successful extubation inpatients with ARDS was not affected by RRT strategy (P = 0.43) Conclusions: Early RRT initiation strategy was not associated with any improvement of 60-day mortality in patients with severe acute kidney injury and septic shock or ARDS. Unnecessary and potentially risky procedures might often be avoided in these fragile populations.