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The degassing of CO2 and S from arc volcanoes is fundamentally important to global climate, eruption forecasting, ore deposits, and the cycling of volatiles through subduction zones. However, all existing thermodynamic/empirical models have difficulties reproducing CO2‐H2O‐S trends observed in melt inclusions and provide widely conflicting results regarding the relationships between pressure and CO2/SO2 in the vapor. In this study, we develop an open‐source degassing model, Sulfur_X, to track the evolution of S, CO2, H2O, and redox states in melt and vapor in ascending mafic‐intermediate magma. Sulfur_X describes sulfur degassing by parameterizing experimentally derived sulfur partition coefficients for two equilibria: RxnI. FeS (m) + H2O (v) →$\\to $  H2S (v) + FeO (m), and RxnII. CaSO4(m) →$\\to $  SO2 (v) + O2 (v) + CaO (m), based on the sulfur speciation in the melt (m) and co‐existing vapor (v). Sulfur_X is also the first to track the evolution of fO2 and sulfur and iron redox states accurately in the system using electron balance and equilibrium calculations. Our results show that a typical H2O‐rich (4.5 wt.%) arc magma with high initial S6+/ΣS ratio (>0.5) will degas much more (∼2/3) of its initial sulfur at high pressures (>200 MPa) than H2O‐poor ocean island basalts with low initial S6+/ΣS ratio (<0.1), which will degas very little sulfur until shallow pressures (<50 MPa). The pressure‐S relationship in the melt predicted by Sulfur_X provides new insights into interpreting the CO2/ST ratio measured in high‐T volcanic gases in the run‐up to the eruption. Plain Language Summary Understanding how CO2 and S are emitted from volcanoes, called degassing, is important in interpreting the CO2/ST gas precursors to volcanic eruptions and quantifying the total amount of gases released into the atmosphere that are climatically important. However, existing models show significant discrepancies in predicting the behavior of sulfur during degassing. In this study, we employ a new approach to describe sulfur behavior during magma degassing and develop a new model, Sulfur_X, that successfully reproduces the distinct S, CO2, and H2O degassing behavior recorded in melts from different volcanoes. Sulfur_X shows that sulfur can either degas early at high pressure or late at low pressure during magma ascent to the surface, depending on the initial sulfur speciation and H2O contents in the magma. In addition, sulfur is one of the most commonly measured volcanic gas components used for volcano monitoring. Therefore, the predicted compositional evolution of co‐existing vapor by Sulfur_X during magma ascent bears directly on the interpretation of CO2/ST ratio measured in high‐T volcanic gases and the development of eruption forecast models. Key Points Sulfur_X is a new open‐source magma degassing model that accurately predicts the volatile and redox evolution of ascending arc magmas Sulfur_X shows that sulfur can start degassing in the lower crust or near‐surface, depending on the initial S6+/ΣS and H2O in the melt The vapor compositions predicted by Sulfur_X can be used to interpret the CO2/ST ratios in high‐T volcanic gases, an eruption precursor

Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies. The DATA study showed that combined teriparatide and denosumab increased bone mineral density more than either drug alone. Discontinuing teriparatide and denosumab, however, results in rapidly declining bone mineral density. In this DATA-Switch study, we aimed to assess the changes in bone mineral density in postmenopausal osteoporotic women who transitioned between treatments. This randomised controlled trial (DATA-Switch) is a preplanned extension of the denosumab and teriparatide administration study (DATA), in which 94 postmenopausal osteoporotic women were randomly assigned to receive 24 months of teriparatide (20 mg daily), denosumab (60 mg every 6 months), or both drugs. In DATA-Switch, women originally assigned to teriparatide received denosumab (teriparatide to denosumab group), those originally assigned to denosumab received teriparatide (denosumab to teriparatide group), and those originally assigned to both received an additional 24 months of denosumab alone (combination to denosumab group). Bone mineral density at the spine, hip, and wrist were measured 6 months, 12 months, 18 months, and 24 months after the drug transitions as were biochemical markers of bone turnover. The primary endpoint was the percent change in posterior-anterior spine bone mineral density over 4 years. Between-group changes were assessed by one-way analysis of variance in our modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00926380. Between Sept 27, 2011, and Jan 28, 2013, eligible women from the DATA study were enrolled into DATA-Switch. Of 83 potential enrollees from the DATA study, 77 completed at least one post-baseline visit. After 48 months, the primary outcome of mean spine bone mineral density increased by 18·3% (95% CI 14·9–21·8) in 27 women in the teriparatide to denosumab group, 14·0% (10·9–17·2) in 27 women the denosumab to teriparatide group, and 16·0% (14·0–18·0) in 23 women in the combination to denosumab group, although this increase did not differ significantly between groups (for between-group comparisons, p=0·13 for the teriparatide to denosumab group vs the denosumab to teriparatide group, p=0·30 for the teriparatide to denosumab group vs the combination to denosumab group, and p=0·41 for the denosumab to teriparatide group vs the combination to denosumab group). For the bone mineral density secondary outcomes, total hip bone mineral density increased more in the teriparatide to denosumab group (6·6% [95% CI 5·3–7·9]) than in the denosumab to teriparatide group (2·8% [1·3–4·2], p=0·0002), but had the greatest increase in the combination to denosumab group (8·6% [7·1–10·0]; p=0·0446 vs the teriparatide to denosumab group, p<0·0001 vs the denosumab to teriparatide group). Similarly, femoral neck bone mineral density increased more in the teriparatide to denosumab group (8·3% [95% CI 6·1–10·5]) and the combination to denosumab group (9·1% [6·1–12·0]) than in the denosumab to teriparatide group (4·9% [2·2–7·5]; p=0·0447 for teriparatide to denosumab vs denosumab to teriparatide, p=0·0336 for combination to denosumab vs denosumab to teriparatide). Differences between the combination to denosumab group and the teriparatide to denosumab group did not differ significantly (p=0·67). After 48 months, radius bone mineral density was unchanged in the teriparatide to denosumab group (0·0% [95% CI −1·3 to 1·4]), whereas it decreased by −1·8% (−5·0 to 1·3) in the denosumab to teriparatide group, and increased by 2·8% (1·2–4·4) in the combination to denosumab group (p=0·0075 for the teriparatide to denosumab group vs the combination to denosumab group; p=0·0099 for the denosumab to teriparatide group vs the combination to denosumab group). One participant in the denosumab to teriparatide group had nephrolithiasis, classified as being possibly related to treatment. In postmenopausal osteoporotic women switching from teriparatide to denosumab, bone mineral density continued to increase, whereas switching from denosumab to teriparatide results in progressive or transient bone loss. These results should be considered when choosing the initial and subsequent management of postmenopausal osteoporotic patients. Amgen, Eli Lilly, and National Institutes of Health.

Face-to-face brief interventions for problem drinking are effective, but they have found limited implementation in routine care and the community. Internet-based interventions could overcome this treatment gap. We investigated effectiveness and moderators of treatment outcomes in internet-based interventions for adult problem drinking (iAIs). Systematic searches were performed in medical and psychological databases to 31 December 2016. A one-stage individual patient data meta-analysis (IPDMA) was conducted with a linear mixed model complete-case approach, using baseline and first follow-up data. The primary outcome measure was mean weekly alcohol consumption in standard units (SUs, 10 grams of ethanol). Secondary outcome was treatment response (TR), defined as less than 14/21 SUs for women/men weekly. Putative participant, intervention, and study moderators were included. Robustness was verified in three sensitivity analyses: a two-stage IPDMA, a one-stage IPDMA using multiple imputation, and a missing-not-at-random (MNAR) analysis. We obtained baseline data for 14,198 adult participants (19 randomised controlled trials [RCTs], mean age 40.7 [SD = 13.2], 47.6% women). Their baseline mean weekly alcohol consumption was 38.1 SUs (SD = 26.9). Most were regular problem drinkers (80.1%, SUs 44.7, SD = 26.4) and 19.9% (SUs 11.9, SD = 4.1) were binge-only drinkers. About one third were heavy drinkers, meaning that women/men consumed, respectively, more than 35/50 SUs of alcohol at baseline (34.2%, SUs 65.9, SD = 27.1). Post-intervention data were available for 8,095 participants. Compared with controls, iAI participants showed a greater mean weekly decrease at follow-up of 5.02 SUs (95% CI -7.57 to -2.48, p < 0.001) and a higher rate of TR (odds ratio [OR] 2.20, 95% CI 1.63-2.95, p < 0.001, number needed to treat [NNT] = 4.15, 95% CI 3.06-6.62). Persons above age 55 showed higher TR than their younger counterparts (OR = 1.66, 95% CI 1.21-2.27, p = 0.002). Drinking profiles were not significantly associated with treatment outcomes. Human-supported interventions were superior to fully automated ones on both outcome measures (comparative reduction: -6.78 SUs, 95% CI -12.11 to -1.45, p = 0.013; TR: OR = 2.23, 95% CI 1.22-4.08, p = 0.009). Participants treated in iAIs based on personalised normative feedback (PNF) alone were significantly less likely to sustain low-risk drinking at follow-up than those in iAIs based on integrated therapeutic principles (OR = 0.52, 95% CI 0.29-0.93, p = 0.029). The use of waitlist control in RCTs was associated with significantly better treatment outcomes than the use of other types of control (comparative reduction: -9.27 SUs, 95% CI -13.97 to -4.57, p < 0.001; TR: OR = 3.74, 95% CI 2.13-6.53, p < 0.001). The overall quality of the RCTs was high; a major limitation included high study dropout (43%). Sensitivity analyses confirmed the robustness of our primary analyses. To our knowledge, this is the first IPDMA on internet-based interventions that has shown them to be effective in curbing various patterns of adult problem drinking in both community and healthcare settings. Waitlist control may be conducive to inflation of treatment outcomes.

Unprecedented change in the US health care system is being driven by the rapid uptake of health information technology and national investments in multi-institution research networks comprising academic centers, health care delivery systems, and other health system components. An example of this changing landscape is Optum Labs, a novel network \"node\" that is bringing together new partners, data, and analytic techniques to implement research findings in health care practice. Optum Labs was founded in early 2013 by Mayo Clinic and Optum, a commercial data, infrastructure services, and care organization that is part of UnitedHealth Group. Optum Labs now has eleven collaborators and a database of deidentified information on more than 150 million people that is compliant with the Health Insurance Portability and Accountability Act (HIPAA) of 1996. This article describes the early progress of Optum Labs. The combination of the diverse collaborator perspectives with rich data, including deep patient and provider information, is intended to reveal new insights about diseases, treatments, and patients' behavior to guide changes in practice. Practitioners' involvement in agenda setting and translation of findings into practical care innovations accelerates the implementation of research results. Furthermore, feedback loops from the clinic help Optum Labs expand on successes and give quick attention to challenges as they emerge.

The conflict in Gaza and Israel transcends faith, race, and nationality. As healthcare professionals committed to principles of dignity, compassion, respect for life, and alleviating human suffering, we should be at the forefront of discussions

Background Psychological therapies provided in primary care are usually briefer than in secondary care. There has been no recent comprehensive review comparing their effectiveness for common mental health problems. We aimed to compare the effectiveness of different types of brief psychological therapy administered within primary care across and between anxiety, depressive and mixed disorders. Methods Meta-analysis and meta-regression of randomized controlled trials of brief psychological therapies of adult patients with anxiety, depression or mixed common mental health problems treated in primary care compared to primary care treatment as usual. Results Thirty-four studies, involving 3962 patients, were included. Most were of brief cognitive behaviour therapy (CBT; n = 13), counselling ( n = 8) or problem solving therapy (PST; n = 12). There was differential effectiveness between studies of CBT, with studies of CBT for anxiety disorders having a pooled effect size [ d -1.06, 95% confidence interval (CI) -1.31 to -0.80] greater than that of studies of CBT for depression ( d -0.33, 95% CI -0.60 to -0.06) or studies of CBT for mixed anxiety and depression ( d -0.26, 95% CI -0.44 to -0.08). Counselling for depression and mixed anxiety and depression ( d -0.32, 95% CI -0.52 to -0.11) and problem solving therapy (PST) for depression and mixed anxiety and depression ( d -0.21, 95% CI -0.37 to -0.05) were also effective. Controlling for diagnosis, meta-regression found no difference between CBT, counselling and PST. Conclusions Brief CBT, counselling and PST are all effective treatments in primary care, but effect sizes are low compared to longer length treatments. The exception is brief CBT for anxiety, which has comparable effect sizes.

Osteolytic lesions (OL) characterize symptomatic multiple myeloma. The mechanisms of how malignant plasma cells (PC) cause OL in one region while others show no signs of bone destruction despite subtotal infiltration remain unknown. We report on a single-cell RNA sequencing (scRNA-seq) study of PC obtained prospectively from random bone marrow aspirates (BM) and paired imaging-guided biopsies of OL. We analyze 148,630 PC from 24 different locations in 10 patients and observe vast inter- and intra-patient heterogeneity based on scRNA-seq analyses. Beyond the limited evidence for spatial heterogeneity from whole-exome sequencing, we find an additional layer of complexity by integrated analysis of anchored scRNA-seq datasets from the BM and OL. PC from OL are characterized by differentially expressed genes compared to PC from BM, including upregulation of genes associated with myeloma bone disease like DKK1 , HGF and TIMP-1 as well as recurrent downregulation of JUN/FOS , DUSP1 and HBB . Assessment of PC from longitudinally collected samples reveals transcriptional changes after induction therapy. Our study contributes to the understanding of destructive myeloma bone disease. Osteolytic lesions (OL) are frequent in multiple myeloma (MM), but are poorly understood. Here, the authors characterise OLs in MM patient samples using single-cell RNA-seq, revealing genes that are specifically regulated in OL compared to random bone marrow aspirates and that reflect the response to induction therapy.

This study explores the impact of a virtual international program on promoting global experiences among teacher education students in the United States (US) and peers in Zimbabwe. Through this program, participants engaged in asynchronous dialogues, collaborations, and exchanges with peers overseas, in which they exchanged ideas on digital literacy and media literacy projects. Results indicate a notable enhancement in the US students’ abilities to engage with global issues and comprehend cultural differences through these dialogues. There are three key themes associated with global learning that emerged as a result of this study: (1) the crucial role of authentic discussions and exchanges, (2) the value of virtual online programs in providing global experiences, and (3) the influence of these engagements on enhancing intercultural literacy. This study highlights the potential for international collaboration in fostering authentic dialogue and understanding among students from diverse cultural backgrounds. The collaborative project served as a bridge between the US and Zimbabwe, providing participants with a platform for rich cultural exchanges and reflections on equitable access to technology and educational opportunities. Overall, this study highlights the importance of virtual international programs and the potential for international collaboration to enhance teacher education students’ ability to engage in meaningful international discourse and collaboration.

Peralkaline rhyolites are a rare magma type, typically associated with continental rift settings, and characterised by excess alkalis relative to alumina and a moderate-low viscosity compared to calc-alkaline equivalents. Despite their prevalence in extensional rift settings, such as the Main Ethiopian Rift, eruption dynamics of peralkaline magmas are poorly understood and have never been directly observed. To address the knowledge gap, this study investigates the style and dynamics of the ~ 87 ka explosive eruption at Baricha volcano as a case study. This eruption deposited widespread pumice lapilli fall and pyroclastic density currents, which provide valuable information on pre- and syn-eruptive magmatic processes. By examining the physical and textural features of the eruption products at different stratigraphic levels, we reconstruct eruption dynamics over time. Our analysis reveals that the eruption had three distinct phases, each characterised by different types of tephra fall deposits and associated with different plume and vent conditions. Specifically, deposits of phases 1 and 3 were characterised by massive and well-sorted tephra falls indicative of sustained plume behaviour, while phase 2 deposits were bedded, lithic-rich (i.e. non-juvenile fragments) tephra falls, and pyroclastic density current deposit associated with an unsteady plume and vent-widening phase. The pumice (8–16 mm size fraction) from this eruption is microlite-free, with a bulk density of 400–700 kg m −3 and > 60% total vesicularity. The vesicle size distribution is polymodal, with the most frequent size ranging from 0.001 to 2.4 mm and an estimated vesicle number density of 0.07*10 7 to 1.6*10 7  mm −3 . The textural observations suggest rapid nucleation occurred during the late phases of magma ascent. Calculated decompression rates of the ascending magma were 0.07–5.6 MPa/s and show a variation between the eruption phases. We conclude that the shift in eruption dynamics alternating between steady to unsteady plume behaviour during the eruption was likely driven by changes in conduit geometry, lithic abundance of the eruptive mixture, decompression rate, and fresh magma injection.

Background Alveolar macrophages (AM) in COPD have fundamentally impaired responsiveness to Toll-like receptor 2 (TLR2) and TLR4 ligands of non-typeable Haemophilus influenzae (NTHI). However, the contribution of innate immune dysfunction to exacerbations of COPD is unexplored. We hypothesised that impaired innate AM responses in COPD extend beyond NTHI to other pathogens and are linked with COPD exacerbations and severity. Methods AMs, obtained by bronchoalveolar lavage from 88 volunteers with stable-to-moderate COPD, were incubated with respiratory pathogens (NTHI, Moraxella catarrhalis (MC), Streptococcus pneumoniae (SP) and TLR ligands lipopolysaccharide, Pam3Cys) and elicited IL-8 and TNF-α were measured by microsphere flow cytometry. NF-κB nuclear translocation was measured by colorimetric assay. AM TLR2 and TLR4 expression was determined by immunolabeling and quantitation of mean fluorescent indices. Participants were monitored prospectively for occurrence of COPD exacerbations for 1 year following bronchoscopy. Non--parametric analyses were used to compare exacerbation-prone and non-exacerbation-prone individuals. Results 29 subjects had at least one exacerbation in the follow-up period (exacerbation-prone) and 59 remained exacerbation-free (non-exacerbation-prone). AMs of exacerbation-prone COPD donors were more refractory to cytokine induction by NTHI (p=0.02), MC (p=0.045) and SP (p=0.046), and to TLR2 (p=0.07) and TLR4 (p=0.028) ligands, and had diminished NF-κB nuclear activation, compared with non-exacerbation-prone counterparts. AMs of exacerbation-prone subjects were more refractory to TLR2 upregulation by MC and SP (p=0.04 each). Conclusions Our results support a paradigm of impaired innate responses of COPD AMs to respiratory pathogens, mediated by impaired TLR responses, underlying a propensity for exacerbations in COPD.