Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care

Spatio-temporal changes in chimpanzee density and abundance in the Greater Mahale Ecosystem, Tanzania

Authors would like to acknowledge the Arcus Foundation, Jane Goodall Institute, United States Agency for International Development (USAID), National Aeronautics and Space Administration (NASA), The Nature Conservancy, and Frankfurt Zoological Society for supporting, facilitating, and funding this work.Species conservation and management require reliable information about animal distribution and population size. Better management actions within a species' range can be achieved by identifying the location and timing of population changes. In the Greater Mahale Ecosystem (GME), western Tanzania, deforestation due to the expansion of human settlements and agriculture, annual burning, and logging are known threats to wildlife. For one of the most charismatic species, the Endangered eastern chimpanzee (Pan troglodytes schweinfurthii), about 75% of the individuals are distributed outside national park boundaries, requiring monitoring and protection efforts over a vast landscape of various protection statuses. These efforts are especially challenging when we lack data on trends in density and population size. To predict spatio-temporal chimpanzee density and abundance across the GME, we employed density surface modelling, fitting a generalised additive model to a ten-year time series data set of nest counts based on line transect surveys. Chimpanzee population declined at an annual rate of 2.41%, including declines of 1.72% in riparian forests (hereafter forests), 2.05% in miombo-woodlands (hereafter woodlands) and 3.45% in non-forests. These population declines were accompanied by ecosystem-wide declines in vegetation types of 1.36% and 0.32% per year for forests and woodlands, respectively; we estimated an annual increase of 1.35% for non-forests. Our model predicted the highest chimpanzee density in forests (0.86 chimpanzees/km2, 95% CI 0.60-1.23; as of 2020), followed by woodlands (0.19, 95% CI 0.12-0.30) and non-forests (0.18, 95% CI 0.10-1.33). Although forests represent only 6% of the landscape, they support nearly a quarter of the chimpanzee population (769 chimpanzees, 95% CI 536-1,103). Woodlands dominate the landscape (71%) and thus support more than a half of the chimpanzee population (2,294; 95% CI 1,420-3,707). The remaining quarter of the landscape is represented by non-forests and supports another quarter of the chimpanzee population (750; 95% CI 408-1,381). Given the pressures on the remaining suitable habitat in Tanzania and the need of chimpanzees to access both forest and woodland vegetation to survive, we urge future management actions to increase resources and expand the efforts to protect critical forest and woodland habitat and promote strategies and policies that more effectively prevent irreversible losses. We suggest that regular monitoring programmes implement a systematic random design to effectively inform and allocate conservation actions and facilitate inter-annual comparisons for trend-monitoring, measuring conservation success and guiding adaptive management.Publisher PDFPeer reviewe

An ancient river landscape preserved beneath the East Antarctic Ice Sheet

The East Antarctic Ice Sheet (EAIS) has its origins ca. 34 million years ago. Since then, the impact of climate change and past fluctuations in the EAIS margin has been reflected in periods of extensive vs. restricted ice cover and the modification of much of the Antarctic landscape. Resolving processes of landscape evolution is therefore critical for establishing ice sheet history, but it is rare to find unmodified landscapes that record past ice conditions. Here, we discover an extensive relic pre-glacial landscape preserved beneath the central EAIS despite millions of years of ice cover. The landscape was formed by rivers prior to ice sheet build-up but later modified by local glaciation before being dissected by outlet glaciers at the margin of a restricted ice sheet. Preservation of the relic surfaces indicates an absence of significant warm-based ice throughout their history, suggesting any transitions between restricted and expanded ice were rapid

Novel Approaches to Detect Serum Biomarkers for Clinical Response to Interferon-β Treatment in Multiple Sclerosis

Interferon beta (IFNβ) is the most common immunomodulatory treatment for relapsing-remitting multiple sclerosis (RRMS). However, some patients fail to respond to treatment. In this study, we identified putative clinical response markers in the serum and plasma of people with multiple sclerosis (MS) treated with IFNβ. In a discovery-driven approach, we use 2D-difference gel electrophoresis (DIGE) to identify putative clinical response markers and apply power calculations to identify the sample size required to further validate those markers. In the process we have optimized a DIGE protocol for plasma to obtain cost effective and high resolution gels for effective spot comparison. APOA1, A2M, and FIBB were identified as putative clinical response markers. Power calculations showed that the current DIGE experiment requires a minimum of 10 samples from each group to be confident of 1.5 fold difference at the p<0.05 significance level. In a complementary targeted approach, Cytometric Beadarray (CBA) analysis showed no significant difference in the serum concentration of IL-6, IL-8, MIG, Eotaxin, IP-10, MCP-1, and MIP-1α, between clinical responders and non-responders, despite the association of these proteins with IFNβ treatment in MS

Partitioning the two-leg spin ladder in Ba2Cu1– xZnxTeO6 : from magnetic order through spin-freezing to paramagnetism

E.J.C., O.M., and C.P. acknowledge financial support from the Leverhulme Trust Research Project Grant No. RPG-2017-109. O.M. is grateful for funding via the Leverhulme Trust Early Career Fellowship ECF-2021-170. A.S.G. acknowledges funding through an EPSRC Early Career Fellowship EP/ T011130/1. A.S.G. and H.T. acknowledge funding through the Humboldt Foundation and the Max Planck Institute for Solid State Research. The authors thank the Science and Technology Facilities Council for beamtime allocated at ISIS through proposal RB1990046 (DOI: 10. 5286/ISIS.E.RB1990046) and the Swiss Muon Source at the Paul Scherrer Institute through proposal numbers 20150959 and 20211440. The authors are grateful for access to the MPMS3 instrument at The Royce Discovery Centre at the University of Sheffield (EPSRC grant no. EP/R00661X/1) and the PPMS instrument at the University of St. Andrews (EPSRC grant no. EP/T031441/1).Ba2CuTeO6 has attracted significant attention as it contains a two-leg spin ladder of Cu2+ cations that lies in close proximity to a quantum critical point. Recently, Ba2CuTeO6 has been shown to accommodate chemical substitutions, which can significantly tune its magnetic behavior. Here, we investigate the effects of substitution for non-magnetic Zn2+ impurities at the Cu2+ site, partitioning the spin ladders. Results from bulk thermodynamic and local muon magnetic characterization on the Ba2Cu1 – xZnxTeO6 solid solution (0 ≤ x ≤ 0.6) indicate that Zn2+ partitions the Cu2+ spin ladders into clusters and can be considered using the percolation theory. As the average cluster size decreases with increasing Zn2+ substitution, there is an evolving transition from long-range order to spin-freezing as the critical cluster size is reached between x = 0.1 to x = 0.2, beyond which the behavior became paramagnetic. This demonstrates well-controlled tuning of the magnetic disorder, which is highly topical across a range of low-dimensional Cu2+-based materials. However, in many of these cases, the chemical disorder is also relatively strong in contrast to Ba2CuTeO6 and its derivatives. Therefore, Ba2Cu1 – xZnxTeO6 provides an ideal model system for isolating the effect of defects and segmentation in low-dimensional quantum magnets.Publisher PDFPeer reviewe

NO-Donating Aspirin and Aspirin Partially Inhibit Age-Related Atherosclerosis but Not Radiation-Induced Atherosclerosis in ApoE Null Mice

BACKGROUND: We previously showed that irradiation to the carotid arteries of ApoE(-/-) mice accelerated the development of macrophage-rich, inflammatory atherosclerotic lesions, prone to intra-plaque hemorrhage. In this study we investigated the potential of anti-inflammatory and anti-coagulant intervention strategies to inhibit age-related and radiation-induced atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: ApoE(-/-) mice were given 0 or 14 Gy to the neck and the carotid arteries and aortic arches were harvested at 4 or 30 weeks after irradiation. Nitric oxide releasing aspirin (NCX 4016, 60 mg/kg/day) or aspirin (ASA, 30 or 300 mg/kg/day) were given continuously in the chow. High dose ASA effectively blocked platelet aggregation, while the low dose ASA or NCX 4016 had no significant effect on platelet aggregation. High dose ASA, but not NCX 4016, inhibited endothelial cell expression of VCAM-1 and thrombomodulin in the carotid arteries at 4 weeks after irradiation; eNOS and ICAM-1 levels were unchanged. After 30 weeks of follow-up, NCX 4016 significantly reduced the total number of lesions and the number of initial macrophage-rich lesions in the carotid arteries of unirradiated mice, but these effects were not seen in the brachiocephalic artery of the aortic arch (BCA). In contrast, high dose ASA lead to a decrease in the number of initial lesions in the BCA, but not in the carotid artery. Both high dose ASA and NCX 4016 reduced the collagen content of advanced lesions and increased the total plaque burden in the BCA of unirradiated mice. At 30 weeks after irradiation, neither NCX 4016 nor ASA significantly influenced the number or distribution of lesions, but high dose ASA lead to formation of collagen-rich "stable" advanced lesions in carotid arteries. The total plaque area of the irradiated BCA was increased after ASA, but the plaque burden was very low compared with the carotid artery. CONCLUSIONS/SIGNIFICANCE: The development and characteristics of radiation-induced atherosclerosis varied between different arteries but could not be circumvented by anti-inflammatory and anti-coagulant therapies. This implicates other underlying mechanistic pathways compared to age-related atherosclerosis

Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens

Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition

Implementation of high-sensitivity cardiac troponin and risk of myocardial infarction or death at 5 years: stepped-wedge, cluster-randomised controlled trial

AbstractObjective: To evaluate the impact of implementing a high-sensitivity cardiac troponin I assay on long-term outcomes in patients with suspected acute coronary syndromeDesign: Secondary observational analysis of a stepped-wedge cluster-randomised controlled trial.Setting: Ten secondary and tertiary care centresParticipants: Consecutive patients with suspected acute coronary syndrome (n=48,282; 47% women) were included in this trial. Myocardial injury was defined as any high-sensitivity cardiac troponin I concentration &gt;99th centile of 16 ng/L in women and 34 ng/L in men.Intervention: Hospital sites were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation of a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds.Main Outcome Measures: Subsequent myocardial infarction or death at 5 years.Results: Overall, 10,360 patients had cardiac troponin concentrations greater than the 99th centile of whom 1,771 (17%) were reclassified by the high-sensitivity assay. The 5-year incidence of subsequent myocardial infarction or death before and after implementation of the high-sensitivity assay was 29% (5,588/18,978) versus 26% (7,591/29,304), respectively, in all patients (adjusted hazard ratio [aHR] 0.97 [95% CI 0.93 to 1.01]), and 63% (456/720) versus 54% (567/1,051) in those reclassified by the high-sensitivity assay (aHR 0.82 [0.72-0.94]). Following implementation, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischemic myocardial injury (aHR 0·83 [0·75-0·91]), but not in those with type 1 or type 2 myocardial infarction (aHR 0·92 [0·83-1·01] and 0·98 [0·84-1·14]).Conclusions: In patients with suspected acute coronary syndrome, implementation of a high-sensitivity cardiac troponin assay reduced the risk of subsequent myocardial infarction or death at 5 years in those reclassified by the high-sensitivity assay. Improvements in outcome were greatest in patients with non-ischemic myocardial injury suggesting a broader benefit beyond the identification of myocardial infarction.<br/

A multiplexed protein microarray for the simultaneous serodiagnosis of human immunodeficiency virus/hepatitis C virus infection and typing of whole blood

All donor blood samples must be tested pretransfusion to determine the donor blood type. Standard testing protocols require that assays be performed for important bloodborne pathogens such as hepatitis C, syphilis, hepatitis B, and human immunodeficiency virus. We have demonstrated proof of the concept that a protein microarray can type whole blood and detect antibody to significant pathogens simultaneously from the same donor blood sample. The data collected demonstrate the ability of the array to accurately type blood samples while also detecting the presence of antibodies against both human immunodeficiency virus and hepatitis C virus. In conclusion, we have successfully developed a platform capable of typing human whole blood samples, while at the same time testing for the presence of antibodies specific for human immunodeficiency virus/hepatitis C virus. The major benefits of this system are its amenability to expansion with additional assays, for example, rhesus typing and syphilis and/or hepatitis B virus detection, and also the adaptability of the assay to higher-throughput analysis, currently 16 individual samples per slide, but readily expandable to a 96-well format