How COVID-19 has changed medical research funding.

Here, we consider how the lessons we learned in 2020 from funding COVID-19 research could have a long-term impact on the way that we fund medical research. We look back at how UK government funding for COVID-19 medical research evolved, beginning with the early calls for proposals in February that pump-primed funding for vaccines and therapeutics, and culminating in the launch of the government's National Core Studies programme in October. We discuss how the research community mobilized to submit and review grants more rapidly than ever before, against a background of laboratory and office closures. We also highlight the challenges of running clinical trials as the number of hospitalized patients fluctuated with different waves of the disease.

Taking Risk: Early Results From Teaching Hospitals' Participation in the Center for Medicare and Medicaid Innovation Bundled Payments for Care Improvement Initiative.

The authors describe observations from the 27 teaching hospitals constituting the Association of American Medical Colleges (AAMC) cohort in the Center for Medicare and Medicaid Innovation (CMMI) Bundled Payments for Care Improvement (BPCI) initiative. CMMI introduced BPCI in August 2011 and selected the first set of participants in January 2013. BPCI participants enter into Medicare payment arrangements for episodes of care for which they take financial risk. The first round of participants entered risk agreements on October 1, 2013 and January 1, 2014. In April 2014, CMMI selected additional participants who started taking financial risk in 2015. Selected episodes include congestive heart failure (CHF), major joint replacement (MJR), and cardiac valve surgery. The AAMC cohort of participating hospitals selected clinical conditions on the basis of patient volume, opportunity to impact savings and quality, organizational and clinical team readiness, and prior process improvement experience. Early financial results suggest that focused attention to postacute care utilization and outcomes, rapid changes in care processes, program pricing rules, and team composition drove savings and losses. The first cohort of participants generated savings in MJR, CHF, and cardiac valve episodes; losses were experienced in stroke, percutaneous coronary intervention, and spine surgery. Although about one-quarter of U.S. teaching hospitals are participating in BPCI, the proliferation of existing and new payment models, as well as the 2015 announcement to increasingly pay providers according to value, mandates close scrutiny of program outcomes. The authors conclude by proposing additional opportunities for research related to alternative payment models.

The European Cancer Patient's Bill of Rights, update and implementation 2016.

In this implementation phase of the European Cancer Patient's Bill of Rights (BoR), we confirm the following three patient-centred principles that underpin this initiative:The right of every European citizen to receive the most accurate information and to be proactively involved in his/her care.The right of every European citizen to optimal and timely access to a diagnosis and to appropriate specialised care, underpinned by research and innovation.The right of every European citizen to receive care in health systems that ensure the best possible cancer prevention, the earliest possible diagnosis of their cancer, improved outcomes, patient rehabilitation, best quality of life and affordable health care. The key aspects of working towards implementing the BoR are:Agree our high-level goal. The vision of 70% long-term survival for patients with cancer in 2035, promoting cancer prevention and cancer control and the associated progress in ensuring good patient experience and quality of life.Establish the major mechanisms to underpin its delivery. (1) The systematic and rigorous sharing of best practice between and across European cancer healthcare systems and (2) the active promotion of Research and Innovation focused on improving outcomes; (3) Improving access to new and established cancer care by sharing best practice in the development, approval, procurement and reimbursement of cancer diagnostic tests and treatments.Work with other organisations to bring into being a Europe based centre that will (1) systematically identify, evaluate and validate and disseminate best practice in cancer management for the different countries and regions and (2) promote Research and Innovation and its translation to maximise its impact to improve outcomes.

Proceedings: international regulatory considerations on development pathways for cell therapies.

Regenerative medicine is a rapidly evolving field that faces novel scientific and regulatory challenges. In September 2013, the International Workshop on Regulatory Pathways for Cell Therapies was convened to discuss the nature of these challenges and potential solutions and to highlight opportunities for potential convergence between different regulatory bodies that might assist the field's development. The workshop discussions generated potentially actionable steps in five main areas that could mitigate cell therapy development pathway risk and accelerate moving promising therapies to patients. These included the need for convergence of regulatory guidelines on donor eligibility and suitability of lines for use in clinical trials and subsequent commercialization for cell therapies to move forward on a global basis; the need to challenge and encourage investigators in the regenerative medicine field to share information and provide examples of comparability studies related to master cell banks; the need for convergence of guidelines across regulatory jurisdictions on requirements for tumorigenicity studies, based on particular cell types and on biodistribution studies; the need to increase transparency in sharing clinical trial information more broadly and disseminating results more rapidly; and the need to establish a forum for sharing the experiences of various approaches being developed to expedite regulatory approvals and access for patients to innovative cell and regenerative therapies in the different regulatory jurisdictions and to assess their potential strengths and weaknesses.

The return of capitation preparing for population-based health care.

To succeed under population-based health care, organizations need to understand thoroughly how this approach differs from traditional fee-for-service health care. To manage care under capitation, the contracting organization should have a population of sufficient size and a clear means of assigning patients to that population. To assess performance, the organization requires metrics that view performance in terms of per member per month, while avoiding common pitfalls of misapplying such metrics.

The Medicare bundled payment pilot program participation considerations.

The Medicare bundled payment pilot program is scheduled to begin in January 2013 and will run for five years. The program holds the promise of increased alignment between hospitals and physicians, presenting opportunities for hospital cost reduction and improvements in quality. Nonetheless, the program carries fixed costs and assumption of risks that hospitals need to evaluate as they deliberate over whether to seek to participate in the program.

Phonon-roton modes and localized Bose-Einstein condensation in liquid helium under pressure in nanoporous media.

We show, using inelastic neutron scattering, that liquid helium in porous media, two gelsils and MCM-41, supports a phonon-roton mode up to a pressure of 36-37 bars only. Modes having the highest energy ("maxons") broaden and become unobservable at the lowest pressures (p approximately 26 bars) while rotons survive to the highest pressure. By comparing with the superfluid density observed by Yamamoto and co-workers in gelsil, we propose that there is a Bose glass phase containing islands of BEC surrounding the superfluid phase.

The cholesterol transporter ABCG1 modulates the subcellular distribution and proteolytic processing of beta-amyloid precursor protein.

Although intracellular cholesterol levels are known to influence the proteolysis of beta-amyloid precursor protein (APP), the effect of specific genes that regulate cholesterol metabolism on APP processing remains poorly understood. The cholesterol transporter ABCG1 facilitates cholesterol efflux to HDL and is expressed in brain. Notably, the human ABCG1 gene maps to chromosome 21q22.3, and individuals with Down syndrome (DS) typically manifest with Alzheimer's disease (AD) neuropathology in their 30s. Here, we demonstrate that expression of ABCG1 enhances amyloid-beta protein (Abeta) production in transfected HEK cells in a manner that requires functional cholesterol transporter activity. ABCG1-expressing cells also exhibit increased secreted APP (sAPP)alpha and sAPPbeta secretion and display increased cell surface-associated APP. These results suggest that ABCG1 increases the availability of APP as a secretase substrate for both the amyloidogenic and nonamyloidogenic pathways. In vivo, ABCG1 mRNA levels are 2-fold more abundant in DS brain compared with age- and sex-matched normal controls. Finally, both Abeta and sAPPalpha levels are increased in DS cortex relative to normal controls. These findings suggest that altered cholesterol metabolism and APP trafficking mediated by ABCG1 may contribute to the accelerated onset of AD neuropathology in DS.