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Background Peer health navigators (PHNs) work with their own communities to provide health navigation support and connect with patients through shared experience and identity. The aim of this study was to explore the role of PHNs in the Australian health system from the perspective of managers and experts, with a focus on understanding how to build and sustain this workforce in Australia. Methods Individuals who employ and manage PHNs, as well as subject matter experts in the navigation field from a range of health and academic organisations across Australia, participated in semi‐structured interviews. A descriptive qualitative approach based on naturalistic inquiry was used to analyse the interview data. Themes were framed around an adapted socio‐ecological model using four levels: individual, interpersonal, organisational and societal (combined community and policy). Results Seventeen themes were identified within the four levels of the adapted socio‐ecological model: individual (personal attributes, knowledge and skills, lived experience), interpersonal (boundary setting: professional, boundary setting: professional meets personal, boundary setting: self‐care, supervision and debriefing), organisational (recruitment, qualifications and prerequisites, clear job description and expectations, training, role duties and tasks) and societal (value of peer navigators in Australia, government support, funding, strategic approach to workforce planning, workforce governance). Conclusion PHNs are a valuable part of the Australian health system. A cohesive, strategic, national approach is required to ensure the development of the workforce and the sustainability of programs and allow for navigators to be embedded within the Australian health system. Patient or Public Contribution This study is part of a larger project that developed formal education and training courseware materials for health navigators in Australia. The materials were co‐designed with patients, managers and subject matter experts. In this paper, we sought the perspective from managers and experts across Australia who work with diverse groups of patients.

Background There is a great deal of variation in the design and delivery of the peer health navigator role, making it difficult to adapt role responsibilities into context. In this study, we aimed to co‐design a bicultural peer health navigator (BPHN) role to meet the needs of culturally and linguistically diverse (CALD) people from Pacific Islander, Māori and Arabic‐speaking backgrounds. Methods A two‐phase co‐design approach involving workshops with follow‐up member checking via interview was used to gain insight into factors affecting patient interaction and access barriers to health services. Results Barriers described by participants emerged under five major themes—overcoming language barriers, improving communication, navigation and access to information, appointment reminders, and health and social services education in the community. Conclusion Clear tasks for the BPHN role were identified by the participants to improve accessibility and usage of healthcare services. Future work should involve feasibility testing with the support and involvement of community members, BPHNs and their supervisors and importantly health service leaders. Patient or Public Contribution Four of the authors were employed as bicultural peer health navigators (BPHNs) who engaged their communities to organise and conduct these workshops in their preferred language. This approach enabled an inclusive environment for the participants to share their thoughts and experiences. The proposed roles for a BPHN were generated from the workshop discussions. The BPHNs conducted the semi‐structured verification interviews with the workshop participants. The thematic analysis was conducted by two of the BPHNs, with one being the primary author.

Peripheral nerve blockade is associated with excellent patient outcomes after surgery; however, neurologic and other complications can be devastating for the patient. This article reports the development and preliminary results of a multicenter audit describing the quality and safety of peripheral nerve blockade. From January 2006 to May 2008, patients who received peripheral nerve blockade had data relating to efficacy and complications entered into databases. All patients who received nerve blocks performed by all anesthetists during each hospital's contributing period were included. Patients were followed up by phone to detect potential neurologic complications. The timing of follow-up was either at 7 to 10 days or 6 weeks postoperatively, depending on practice location and time period. Late neurologic deficits were defined as a new onset of sensory and/or motor deficit consistent with a nerve/plexus distribution without other identifiable cause, and one of the following: electrophysiologic evidence of nerve damage, new neurologic signs, new onset of neuropathic pain in a nerve distribution area, paresthesia in relevant nerve/plexus distribution area. A total of 6950 patients received 8189 peripheral nerve or plexus blocks. Of the 6950 patients, 6069 patients were successfully followed up. In these 6069 patients, there were a total of 7156 blocks forming the denominator for late neurologic complications. Thirty patients (0.5%) had clinical features requiring referral for neurologic assessment. Three of the 30 patients had a block-related nerve injury, giving an incidence of 0.4 per 1000 blocks (95% confidence interval, 0.08-1.1:1000). The incidence of systemic local anesthetic toxicity was 0.98 per 1000 blocks (95% confidence interval, 0.42-1.9:1000). These results indicate that the incidence of serious complications after peripheral nerve blockade is uncommon and that the origin of neurologic symptoms/signs in the postoperative period is most likely to be unrelated to nerve blockade.

Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS. •Neuromuscular blockade is commonly used to enable prone ventilation in COVID-ARDS.•The addition of neuromuscular blockade to prone positioning may improve oxygenation.•Improved oxygenation with neuromuscular blockade is maintained on return to supine.•This effect is sustained across multiple prone positioning episodes.

The Poverty Reduction and Growth Facility (PRGF) is used by the IMF to provide support for countries' implementation of their poverty reduction and growth strategies. A key requirement in the design of PRGF programs is understanding the effects of reform program measures on vulnerable groups-particularly the poor-and how to devise measures to mitigate any negative effects. Poverty and social impact analysis (PSIA) is a critical instrument for pursuing this goal. The IMF has therefore established a small group of staff economists to facilitate the integration of PSIA into PRGF-supported programs. In this book, the group's members review analytical techniques used in PSIA as well as several important topics to which PSIA can make valuable contributions. These reviews should prove useful and interesting to readers interested in PSIA in general and the IMF's PSIA efforts in particular.

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage 1 – 3 . Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity 3 – 5 . In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli. Reanalysis of bipedal trackways from Laetoli site A in Tanzania suggest that the footprints were made by a hominin that coexisted with at least one other hominin species.

Background and Objectives Voriconazole administered concomitantly with flucloxacillin may result in subtherapeutic plasma concentrations as shown in a patient with Staphylococcus aureus sepsis and a probable pulmonary aspergillosis. After switching our patient to posaconazole, therapeutic concentrations were reached. The aim of this study was to first test our hypothesis that flucloxacillin competes with voriconazole not posaconazole for binding to albumin ex vivo, leading to lower total concentrations in plasma. Methods A physiologically based pharmacokinetic (PBPK) model was then applied to predict the mechanism of action of the drug–drug interaction (DDI). The model included non-linear hepatic metabolism and the effect of a severe infectious disease on cytochrome P450 (CYP) enzymes activity. Results The unbound voriconazole concentration remained unchanged in plasma after adding flucloxacillin, thereby rejecting our hypothesis of albumin-binding site competition. The PBPK model was able to adequately predict the plasma concentration of both voriconazole and posaconazole over time in healthy volunteers. Upregulation of CYP3A4, CYP2C9, and CYP2C19 through the pregnane X receptor (PXR) gene by flucloxacillin resulted in decreased voriconazole plasma concentrations, reflecting the DDI observations in our patient. Posaconazole metabolism was not affected, or was only limitedly affected, by the changes through the PXR gene, which agrees with the observed plasma concentrations within the target range in our patient. Conclusions Ex vivo experiments reported that the unbound voriconazole plasma concentration remained unchanged after adding flucloxacillin. The PBPK model describes the potential mechanism driving the drug–drug and drug–disease interaction of voriconazole and flucloxacillin, highlighting the large substantial influence of flucloxacillin on the PXR gene and the influence of infection on voriconazole plasma concentrations, and suggests a more limited effect on other triazoles.

Cells sense the extracellular environment and mechanical stimuli and translate these signals into intracellular responses through mechanotransduction, which alters cell maintenance, proliferation, and differentiation. Here we use a mouse model of trauma-induced heterotopic ossification (HO) to examine how cell-extrinsic forces impact mesenchymal progenitor cell (MPC) fate. After injury, single-cell (sc) RNA sequencing of the injury site reveals an early increase in MPC genes associated with pathways of cell adhesion and ECM-receptor interactions, and MPC trajectories to cartilage and bone. Immunostaining uncovers active mechanotransduction after injury with increased focal adhesion kinase signaling and nuclear translocation of transcriptional coactivator TAZ, inhibition of which mitigates HO. Similarly, joint immobilization decreases mechanotransductive signaling, and completely inhibits HO. Joint immobilization decreases collagen alignment and increases adipogenesis. Further, scRNA sequencing of the HO site after injury with or without immobilization identifies gene signatures in mobile MPCs correlating with osteogenesis, and signatures from immobile MPCs with adipogenesis. scATAC-seq in these same MPCs confirm that in mobile MPCs, chromatin regions around osteogenic genes are open, whereas in immobile MPCs, regions around adipogenic genes are open. Together these data suggest that joint immobilization after injury results in decreased ECM alignment, altered MPC mechanotransduction, and changes in genomic architecture favoring adipogenesis over osteogenesis, resulting in decreased formation of HO.

Programmed death-1 (PD-1) and interleukin-10 (IL-10) impair T cell function during chronic viral infections. Microbial products are now found to inhibit T cell function during HIV infection by upregulating PD-1 and IL-10 production by monocytes. Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4 + T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4 + T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.

Fast and accurate quantum operations of a single spin in room-temperature solids are required in many modern scientific areas, for instance in quantum information, quantum metrology, and magnetometry. However, the accuracy is limited if the Rabi frequency of the control is comparable with the transition frequency of the qubit due to the breakdown of the rotating wave approximation (RWA). We report here an experimental implementation of a control method based on quantum optimal control theory which does not suffer from such restriction. We demonstrate the most commonly used single qubit rotations, i.e. - and -pulses, beyond the RWA regime with high fidelity and , respectively. They are in excellent agreement with the theoretical predictions, and . Furthermore, we perform two basic magnetic resonance experiments both in the rotating and the laboratory frames, where we are able to deliberately 'switch' between the frames, to confirm the robustness of our control method. Our method is general, hence it may immediately find its wide applications in magnetic resonance, quantum computing, quantum optics, and broadband magnetometry.