Political momentum and funding for combatting antimicrobial resistance (AMR) continues to build. Numerous major international and national initiatives aimed at financially incentivising the research and development (R&D) of antibiotics have been implemented. However, it remains unclear how to effectively strengthen the current set of incentive programmes to further accelerate antibiotic innovation. Based on a literature review and expert input, this study first identifies and assesses the major international, European Union, US and UK antibiotic R&D funding programmes. These programmes are then evaluated across market and public health criteria necessary for comprehensively improving the antibiotic market. The current set of incentive programmes are an important initial step to improving the economic feasibility of antibiotic development. However, there appears to be a lack of global coordination across all initiatives, which risks duplicating efforts, leaving funding gaps in the value chain and overlooking important AMR goals. This study finds that incentive programmes are overly committed to early-stage push funding of basic science and preclinical research, while there is limited late-stage push funding of clinical development. Moreover, there are almost no pull incentives to facilitate transition of antibiotic products from early clinical phases to commercialisation, focus developer concentration on the highest priority antibiotics and attract large pharmaceutical companies to invest in the market. Finally, it seems that antibiotic sustainability and patient access requirements are poorly integrated into the array of incentive mechanisms.
Global research and development (R&D) pipelines for diseases that disproportionately affect African countries appear to be inadequate, with governments struggling to prioritise investment in R&D. This article provides insights into the sources of investment in health science research, available research capacity and level of research output in Africa. The African region comprises 15% of the world’s population, yet only accounted for 1.1% of global investments in R&D in 2016. There were substantial disparities within the continent, with Egypt, Nigeria and South Africa contributing 65.7% of the total R&D spending. In most countries of the Organisation for Economic Co-operation and Development, the largest source of R&D funding is the private sector. R&D in Africa is mainly funded by the public sector, with significant proportions of financing in many countries coming from international funding. Challenges that limit private sector investment include unstable political environments, poor governance and corruption. Evidence suggests various research output and research capacity limitations in Africa when considering a global context. Metrics that reflect this include university rankings, number of researchers, number of publications, clinical trials networks and pharmaceutical manufacturing capacity. Within the continent there are substantial regional disparities. Incentivising investment is crucial to foster current and future research output and research capacity. This paper outlines some of the many commendable initiatives under way. Innovative and collaborative financing mechanisms can stimulate further investment. Given the vast inequalities across Africa in R&D, strategies need to reflect the different capacities of countries to address this disparity.
Control of chondrocyte pH (pH(i)) determines articular cartilage matrix metabolism. However, the transporters of chondrocytes in situ throughout cartilage zones are unclear, and we tested the hypothesis that chondocytes within the superficial zone (SZ) utilise a HCO(3) (-)-dependent system absent from other zones. Imaging of single BCECF-labelled cells was used to monitor the pH(i) of in situ chondrocytes within the cartilage zones, and also that of cells isolated from the SZ or full depth (FD) explants. Resting pH(i) and intrinsic buffering power (beta(i)) in HEPES-buffered saline was not different between SZ and DZ cells, however the pH(i) of SZ chondrocytes was lower in HCO(3) (-) saline. Ammonium pre-pulse was used to acid-load cells and pH(i) recovery by in situ or isolated SZ chondrocytes shown to be totally dependent on HCO(3) (-). pH(i) recovery rate was significantly (P < 0.05) greater for in situ cells, suggesting that isolation damaged the HCO(3) (-)-dependent system. Recovery of pH(i) by in situ cells was blocked by the anion transport inhibitor DIDS, and partially inhibited by EIPA probably non-specifically. Recovery of pH(i) by acidified MZ or DZ cells or those isolated from FD explants was not affected by HCO(3) (-) (P > 0.05). Na(+)-dependent HCO(3) (-)-(NBC) transporters were identified in SZ chondrocytes by fluorescence immunohistochemistry suggesting that this system might account for the HCO(3) (-)-dependent recovery of pH(i). Bovine articular cartilage chondrocytes possess a HCO(3) (-)-dependent transporter which plays a key role in pH(i) regulation in cells in the SZ, but not in chondrocytes within deeper cartilage zones.
Contemporary cardiac surgery for ACHD performed at a single, tertiary reference centre with a multidisciplinary approach is associated with low mortality and improved functional status. Also, our findings emphasise the point that surgery should not be delayed because of reluctance to reoperate only.
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