Strongly correlated multielectron bunches from interaction with quantum light.

Strongly correlated electron systems are a cornerstone of modern physics, being responsible for groundbreaking phenomena from superconducting magnets to quantum computing. In most cases, correlations in electrons arise exclusively because of Coulomb interactions. In this work, we reveal that free electrons interacting simultaneously with a light field can become highly correlated via mechanisms beyond Coulomb interactions. In the case of two electrons, the resulting Pearson correlation coefficient for the joint probability distribution of the output electron energies is enhanced by more than 13 orders of magnitude compared to that of electrons interacting with the light field in succession (one after another). These highly correlated electrons are the result of momentum and energy exchange between the participating electrons via the external quantum light field. Our findings pave the way to the creation and control of highly correlated free electrons for applications including quantum information and ultrafast imaging.

Free-electron crystals for enhanced X-ray radiation.

Bremsstrahlung-the spontaneous emission of broadband radiation from free electrons that are deflected by atomic nuclei-contributes to the majority of X-rays emitted from X-ray tubes and used in applications ranging from medical imaging to semiconductor chip inspection. Here, we show that the bremsstrahlung intensity can be enhanced significantly-by more than three orders of magnitude-through shaping the electron wavefunction to periodically overlap with atoms in crystalline materials. Furthermore, we show how to shape the bremsstrahlung X-ray emission pattern into arbitrary angular emission profiles for purposes such as unidirectionality and multi-directionality. Importantly, we find that these enhancements and shaped emission profiles cannot be attributed solely to the spatial overlap between the electron probability distribution and the atomic centers, as predicted by the paraxial and non-recoil theory for free electron light emission. Our work highlights an unprecedented regime of free electron light emission where electron waveshaping provides multi-dimensional control over practical radiation processes like bremsstrahlung. Our results pave the way towards greater versatility in table-top X-ray sources and improved fundamental understanding of quantum electron-light interactions.

World Heart Federation Roadmap for Secondary Prevention of Cardiovascular Disease: 2023 Update.

Background: Secondary prevention lifestyle and pharmacological treatment of atherosclerotic cardiovascular disease (ASCVD) reduce a high proportion of recurrent events and mortality. However, significant gaps exist between guideline recommendations and usual clinical practice. Objectives: Describe the state of the art, the roadblocks, and successful strategies to overcome them in ASCVD secondary prevention management. Methods: A writing group reviewed guidelines and research papers and received inputs from an international committee composed of cardiovascular prevention and health systems experts about the article's structure, content, and draft. Finally, an external expert group reviewed the paper. Results: Smoking cessation, physical activity, diet and weight management, antiplatelets, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors, and cardiac rehabilitation reduce events and mortality. Potential roadblocks may occur at the individual, healthcare provider, and health system levels and include lack of access to healthcare and medicines, clinical inertia, lack of primary care infrastructure or built environments that support preventive cardiovascular health behaviours. Possible solutions include improving health literacy, self-management strategies, national policies to improve lifestyle and access to secondary prevention medication (including fix-dose combination therapy), implementing rehabilitation programs, and incorporating digital health interventions. Digital tools are being examined in a range of settings from enhancing self-management, risk factor control, and cardiac rehab. Conclusions: Effective strategies for secondary prevention management exist, but there are barriers to their implementation. WHF roadmaps can facilitate the development of a strategic plan to identify and implement local and national level approaches for improving secondary prevention.

Measuring health equity in the ASEAN region: conceptual framework and assessment of data availability.

BACKGROUND: Existing research on health equity falls short of identifying a comprehensive set of indicators for measurement across health systems. Health systems in the ASEAN region, in particular, lack a standardised framework to assess health equity. This paper proposes a comprehensive framework to measure health equity in the ASEAN region and highlights current gaps in data availability according to its indicator components. METHODS: A comprehensive literature review was undertaken to map out a core set of indicators to evaluate health equity at the health system level. Secondary data collection was subsequently conducted to assess current data availability for ASEAN states in key global health databases, national health accounts, and policy documents. RESULTS: A robust framework to measure health equity was developed comprising 195 indicators across Health System Inputs and Processes, Outputs, Outcomes, and Contextual Factors. Total indicator data availability equated to 72.9% (1423/1950). Across the ASEAN region, the Inputs and Processes sub-component of Health Financing had complete data availability for all indicators (160/160, 100%), while Access to Essential Medicine had the least data available (6/30, 20%). Under Outputs and Outcomes, Coverage of Selected Interventions (161/270, 59.63%) and Population Health (350/350, 100%) respectively had the most data available, while other indicator sub-components had little to none (≤ 38%). 72.145% (384/530) of data is available for all Contextual Factors. Out of the 10 ASEAN countries, the Philippines had the highest data availability overall at 77.44% (151/195), while Brunei Darussalam and Vietnam had the lowest data availability at 67.18% (131/195). CONCLUSIONS: The data availability gaps highlighted in this study underscore the need for a standardised framework to guide data collection and benchmarking of health equity in ASEAN. There is a need to prioritise regular data collection for overlooked indicator areas and in countries with low levels of data availability. The application of this indicator framework and resulting data availability analysis could be conducted beyond ASEAN to enable cross-regional benchmarking of health equity.

Health financing policies during the COVID-19 pandemic and implications for universal health care: a case study of 15 countries.

BACKGROUND: The COVID-19 pandemic was a health emergency requiring rapid fiscal resource mobilisation to support national responses. The use of effective health financing mechanisms and policies, or lack thereof, affected the impact of the pandemic on the population, particularly vulnerable groups and individuals. We provide an overview and illustrative examples of health financing policies adopted in 15 countries during the pandemic, develop a framework for resilient health financing, and use this pandemic to argue a case to move towards universal health coverage (UHC). METHODS: In this case study, we examined the national health financing policy responses of 15 countries, which were purposefully selected countries to represent all WHO regions and have a range of income levels, UHC index scores, and health system typologies. We did a systematic literature review of peer-reviewed articles, policy documents, technical reports, and publicly available data on policy measures undertaken in response to the pandemic and complemented the data obtained with 61 in-depth interviews with health systems and health financing experts. We did a thematic analysis of our data and organised key themes into a conceptual framework for resilient health financing. FINDINGS: Resilient health financing for health emergencies is characterised by two main phases: (1) absorb and recover, where health systems are required to absorb the initial and subsequent shocks brought about by the pandemic and restabilise from them; and (2) sustain, where health systems need to expand and maintain fiscal space for health to move towards UHC while building on resilient health financing structures that can better prepare health systems for future health emergencies. We observed that five key financing policies were implemented across the countries-namely, use of extra-budgetary funds for a swift initial response, repurposing of existing funds, efficient fund disbursement mechanisms to ensure rapid channelisation to the intended personnel and general population, mobilisation of the private sector to mitigate the gaps in public settings, and expansion of service coverage to enhance the protection of vulnerable groups. Accountability and monitoring are needed at every stage to ensure efficient and accountable movement and use of funds, which can be achieved through strong governance and coordination, information technology, and community engagement. INTERPRETATION: Our findings suggest that health systems need to leverage the COVID-19 pandemic as a window of opportunity to make health financing policies robust and need to politically commit to public financing mechanisms that work to prepare for future emergencies and as a lever for UHC. FUNDING: Bill & Melinda Gates Foundation.

Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation.

Bacterial lipopolysaccharide (LPS) induces rapid protein aggregation in human wound fluid. We aimed to characterize these LPS-induced aggregates and their functional implications using a combination of mass spectrometry analyses, biochemical assays, biological imaging, cell experiments, and animal models. The wound-fluid aggregates encompass diverse protein classes, including sequences from coagulation factors, annexins, histones, antimicrobial proteins/peptides, and apolipoproteins. We identified proteins and peptides with a high aggregation propensity and verified selected components through Western blot analysis. Thioflavin T and Amytracker staining revealed amyloid-like aggregates formed after exposure to LPS in vitro in human wound fluid and in vivo in porcine wound models. Using NF-κB-reporter mice and IVIS bioimaging, we demonstrate that such wound-fluid LPS aggregates induce a significant reduction in local inflammation compared with LPS in plasma. The results show that protein/peptide aggregation is a mechanism for confining LPS and reducing inflammation, further emphasizing the connection between host defense and amyloidogenesis.

A review on paying for advanced cancer therapeutics: hard truths and realities in Asia.

Health system expenditure on cancer drugs is rising rapidly in many countries given the high-priced novel treatments as well as the increasing usage due to a growing and ageing global population. The cost of cancer care continues to outstrip other diseases and it presents a global challenge to treatment access and cancer outcomes. Substantial variability exists in drug pricing across Asia, with low- or middle-income countries being heavily impacted. There is an urgent need to practice value-based pricing for oncology drugs. This will incentivize development of higher-value medicine and eliminate waste. Value-based assessments, financing infrastructure to assist appropriate prioritization, establishing domestic innovation and productive capabilities and reducing the unit economics of care are some of the measures that Asian countries should take towards ensuring universal health coverage for cancer care. Asia will need to keep driving cost management measures that are focused on drug pricing and simultaneously, should be encouraged to explore other interventions including centralising expertise for high "learning curve" efficiencies like chimeric antigen receptor (CAR)-T cell therapy. There is a call for more international collaboration within Asia and a continuous need to engage the public within each country, in order to ensure equitable access to effective cancer medications.

The East Asian gut microbiome and its role in oncology: a narrative review.

The field of onco-microbiome is rapidly expanding. Multiple studies have shown the crucial role of gut microbiota in the regulation of nutrient metabolism, immunomodulation and protection against pathogens. Tools for manipulating the gut microbiota include dietary modification and faecal microbiota transfer. Accumulating evidence has also documented the application of specific intestinal microbiome in cancer immunotherapy, notably in enhancing the efficacy of immune checkpoint inhibitors. The aim of this review is to focus on the East Asian microbiome and to provide a current overview of microbiome science and its clinical application in cancer biology and immunotherapy.

Mitigating the impacts of the COVID-19 pandemic on vulnerable populations: Lessons for improving health and social equity.

The COVID-19 pandemic had an inequitable and disproportionate impact on vulnerable populations, reversing decades of progress toward healthy populations and poverty alleviation. This study examines various programmatic tools and policy measures used by governments to support vulnerable populations during the pandemic. A comparative case study of 15 countries representing all World Health Organization's regions offers a comprehensive picture of countries with varying income statuses, health system arrangements and COVID-19 public health measures. Through a systematic desk review and key informant interviews, we report a spectrum of mitigation strategies deployed in these countries to address five major types of vulnerabilities (health, economic, social, institutional and communicative). We found a multitude of strategies that supported vulnerable populations such as migrant workers, sex workers, prisoners, older persons and school-going children. Prioritising vulnerable populations during the early phase of COVID-19 vaccination campaigns, direct financial subsidies and food assistance programmes were the most common measures reported. Additionally, framing public health information and implementing culturally sensitive health promotion interventions helped bridge the communication barriers in certain instances. However, these measures remain insufficient to protect vulnerable populations comprehensively. Our findings point to the need to expand fiscal space for health, enlarge healthcare coverage, incorporate equity principles in all policies, leverage technology, multi-stakeholder co-production of policies and tailored community engagement mechanisms.

Quantum Interference between Fundamentally Different Processes Is Enabled by Shaped Input Wavefunctions.

This work presents a general framework for quantum interference between processes that can involve different fundamental particles or quasi-particles. This framework shows that shaping input wavefunctions is a versatile and powerful tool for producing and controlling quantum interference between distinguishable pathways, beyond previously explored quantum interference between indistinguishable pathways. Two examples of quantum interference enabled by shaping in interactions between free electrons, bound electrons, and photons are presented: i) the vanishing of the zero-loss peak by destructive quantum interference when a shaped electron wavepacket couples to light, under conditions where the electron's zero-loss peak otherwise dominates; ii) quantum interference between free electron and atomic (bound electron) spontaneous emission processes, which can be significant even when the free electron and atom are far apart, breaking the common notion that a free electron and an atom must be close by to significantly affect each other's processes. Conclusions show that emerging quantum wave-shaping techniques unlock the door to greater versatility in light-matter interactions and other quantum processes in general.

Evaluating the Effects of Capacity Building Initiatives and Primary Care Networks in Singapore: Outcome Harvesting of System Changes to Chronic Disease Care Delivery.

The high tertiary healthcare utilisation in Singapore due to an ageing population and increasing chronic disease load has resulted in the establishment of primary care networks (PCNs) for private general practitioners (GPs) to provide team-based, community care for chronic diseases. A total of 22 PCN leaders and programme managers from 10 PCNs participated in online group discussions and a survey. Outcome harvesting was used to retrospectively link the intended and unintended outcomes to the programme initiatives and intermediate results (IRs). The outcomes were generated, refined and verified before shortlisting for analysis. About 134 positive and 22 negative PCN outcomes were observed since inception in 2018. By establishing PCN headquarters and entrusting PCN leaders with the autonomy to run these, as well as focusing policy direction on GP onboarding, GP engagements and clinical governance, the programme successfully harnessed the collective capabilities of GPs. Developments in the organisation (IR1) and monitoring and evaluation (IR4) were the top two contributors for positive and negative outcomes. Sustainable practice and policy changes represented 46% and 20% of the positive outcomes respectively. Sustainable positive outcomes were predominantly contributed by funding, clear programme policy direction and oversight. Conversely, most negative outcomes were due to the limited programme oversight especially in areas not covered by the programme policy.

Approaching the Intrinsic Threshold Breakdown Voltage and Ultrahigh Gain in a Graphite/InSe Schottky Photodetector.

Realizing both ultralow breakdown voltage and ultrahigh gain is one of the major challenges in the development of high-performance avalanche photodetector. Here, it is reported that an ultrahigh avalanche gain of 3 × 105 can be realized in the graphite/InSe Schottky photodetector at a breakdown voltage down to 5.5 V. Remarkably, the threshold breakdown voltage can be further reduced down to 1.8 V by raising the operating temperature, approaching the theoretical limit of 1.5 E g \[{{\cal E}_{\bf g}}\] /e, with E g ${{\cal E}_{\bf g}}$ the bandgap of semiconductor. A 2D impact ionization model is developed and it is uncovered that observation of high gain at low breakdown voltage arises from reduced dimensionality of electron-phonon scattering in the layered InSe flake. These findings open up a promising avenue for developing novel weak-light detectors with low energy consumption and high sensitivity.

The Effect of Health Check-Ups on Health Among the Elderly in China: Evidence From 2011-2018 Longitudinal Data.

Objectives: To assess the effect of health check-ups on health among the elderly Chinese. Methods: The first dataset was panel data extracted from the 2011, 2014, and 2018 waves of the Chinese Longitudinal Health Longevity Survey (CLHLS). The second dataset was cross-sectional data come from CLHLS 2018 linked with the lagged term of health check-ups in CLHLS 2011. Health check-ups were measured by a binary variable annual health check-up (AHC). Health was assessed by a binary variable self-rated health (SRH). A coarsened exact matching method and individual fixed-effects models, as well as logistic regressions were employed. Results: AHC attendance among the elderly increased from 2011 to 2018, with higher utilization of AHC also detected in the rural group. AHC had positive effects on SRH among rural respondents (short-term effect: OR = 1.567, p < 0.05; long-term effect: OR = 3.385, p < 0.001). Conclusion: This study highlights a higher utilization of AHC in rural area, and the effectiveness of AHC in SRH improvement among rural participants. It indicates enhanced access to public healthcare services in rural area and underlying implications of health check-ups for reducing urban-rural health inequalities.

Governance of Assisted Living in Singapore: Lessons for Aging Countries.

A global trend toward aging populations means that the challenge of providing adequate long-term care to older people looms large in many countries. In Singapore, a public discourse revolving around the expansion of assisted living to create age-friendly environments in long-term care has emerged. This study examines Singapore's experience in developing regulations for assisted living by documenting the different levels of regulation in place and by identifying the regulatory gaps remaining to govern assisted living. Anchoring in a conceptual framework on the governance of assisted living, different regulatory components of assisted living at the micro-, meso-, and macro-levels are analyzed. Using a case study method, primary and secondary data examining the experiences of governing and implementing assisted living in Singapore were collected. Analysis was conducted using a thematic analysis approach. Micro- and some macro-level regulations, which include admission assessment, staffing, and infrastructural requirements for assisted living, are maturing and evolving, while meso-level regulations, such as operational management, the monitoring framework, and stipulations for training requirements for staff, remain a work-in-progress in Singapore. The regulations for assisted living are currently primarily guided by soft laws, such as practice guidelines; the government has committed toward enacting permanent regulations for all long-term care facilities with the phased implementation of the Health Care Services Act from 2021 to 2023. We conclude that assisted living, despite the early stage of its development in Singapore, is a viable care model that should be expanded to meet the rising demand for care on the part of a majority of older people, who fall in the middle of the care continuum (that is, they can neither live independently nor need complete institutionalization). We also propose five policy recommendations for all aging countries to strengthen the governance of assisted living in long-term care. These include establishing (i) clear provisions on care quality assessment and the redress of grievance, (ii) minimum standards of care, (iii) differential regulations for assisted living, (iv) routine care assessment, and, (v) applying technology in assisted living facilities to address a shortage of care workers.

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Monoclonal Antibody MHAA4549A in Patients With Acute Uncomplicated Influenza A Infection.

BACKGROUND: MHAA4549A, a human monoclonal antibody targeting the influenza A hemagglutinin stalk, neutralizes influenza A virus in animal and human volunteer challenge studies. We investigated the safety and tolerability, efficacy, and pharmacokinetics of MHAA4549A in outpatients with acute, uncomplicated influenza A infection. METHODS: This was a phase 2, randomized, double-blind, placebo-controlled trial of single intravenous (IV) doses of 3600 mg or 8400 mg of MHAA4549A or IV placebo in adult outpatients testing positive for influenza A. Patients were enrolled across 35 sites in 6 countries. Randomization and dosing occurred within ≤72 hours of symptom onset; the study duration was 14 weeks. The primary end point was the nature and frequency of adverse events (AEs). Secondary end points included median time to alleviation of all influenza symptoms, effects on nasopharyngeal viral load and duration of viral shedding, and MHAA4549A serum pharmacokinetics. RESULTS: Of 125 randomized patients, 124 received study treatment, with 99 confirmed positive for influenza A by central testing. The frequency of AEs between the MHAA4549A and placebo groups was similar; nausea was most common (8 patients; 6.5%). MHAA4549A serum exposure was confirmed in all MHAA4549A-treated patients and was dose-proportional. No hospitalizations or deaths occurred. Between the MHAA4549A and placebo groups, no statistically significant differences occurred in the median time to alleviation of all symptoms, nasopharyngeal viral load, or duration of viral shedding. CONCLUSIONS: While MHAA4549A was safe and well tolerated with confirmed exposure, the antibody did not improve clinical outcomes in patients with acute uncomplicated influenza A infection.