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IntroductionWe sought to evaluate the impact of transitioning a multi-country HIV training program from in-person to online by comparing digital training approaches implemented during the pandemic with in-person approaches employed before COVID-19.MethodsWe evaluated mean changes in pre-and post-course knowledge scores and self-reported confidence scores for learners who participated in (1) in-person workshops (between October 2019 and March 2020), (2) an entirely asynchronous, Virtual Workshops [VW] (between May 2021 and January 2022), and (3) a blended Online Course [OC] (between May 2021 and January 2022) across 16 SSA countries. Learning objectives and evaluation tools were the same for all three groups.ResultsAcross 16 SSA countries, 3023 participants enrolled in the in-person course, 2193 learners participated in the virtual workshop and 527 in the online course. The proportions of women who participated in the VW and OC were greater than the proportion who participated in the in-person course (60.1% and 63.6%, pAcross all domains of HIV knowledge and self-perceived confidence, there was a mean increase between pre- and post-course assessments, regardless of how training was delivered. The greatest percent increase in knowledge scores was among those participating in the in-person course compared to VW or OC formats (13.6% increase vs. 6.0% and 7.6%, pConclusionsIn this multi-country capacity HIV training program, in-person, online synchronous and blended synchronous/asynchronous strategies were effective means of training learners from diverse clinical settings. Online learning approaches facilitated participation from more women and more diverse cadres. However, gains in knowledge and clinical confidence were greater among those participating in in-person learning programs.

Anthropogenic aerosols exert a cooling influence that offsets part of the greenhouse gas warming. Due to their short tropospheric lifetime of only several days, the aerosol forcing responds quickly to emissions. Here, we present and discuss the evolution of the aerosol forcing since 2000. There are multiple lines of evidence that allow us to robustly conclude that the anthropogenic aerosol effective radiative forcing (ERF) - both aerosol- radiation interactions (ERFari) and aerosol-cloud interactions (ERFaci) - has become less negative globally, i.e. the trend in aerosol effective radiative forcing changed sign from negative to positive. Bottom-up inventories show that anthropogenic primary aerosol and aerosol precursor emissions declined in most regions of the world; observations related to aerosol burden show declining trends, in particular of the fine-mode particles that make up most of the anthropogenic aerosols; satellite retrievals of cloud droplet numbers show trends in regions with aerosol declines that are consistent with these in sign, as do observations of top-of-atmosphere radiation. Climate model results, including a revised set that is constrained by observations of the ocean heat content evolution show a consistent sign and magnitude for a positive forcing relative to the year 2000 due to reduced aerosol effects. This reduction leads to an acceleration of the forcing of climate change, i.e. an increase in forcing by 0.1 to 0.3 W m(-2), up to 12 % of the total climate forcing in 2019 compared to 1750 according to the Intergovernmental Panel on Climate Change (IPCC)., Atmospheric Chemistry and Physics, 22 (18), ISSN:1680-7375, ISSN:1680-7367

Anthropogenic aerosols exert a cooling influence that offsets part of the greenhouse gas warming. Due to their short tropospheric lifetime of only up to several days, the aerosol forcing responds quickly to emissions. Here we present and discuss the evolution of the aerosol forcing since 2000. There are multiple lines of evidence that allow to robustly conclude that the anthropogenic aerosol effective radiative forcing – both aerosol-radiation and aerosol-cloud interactions – has become globally less negative, i.e. that the trend in aerosol effective radiative forcing changed sign from negative to positive. Bottom-up inventories show that anthropogenic primary aerosol and aerosol precursor emissions declined in most regions of the world; observations related to aerosol burden show declining trends, in particular of the fine-mode particles that make up most of the anthropogenic aerosols; satellite retrievals of cloud droplet numbers show trends consistent in sign, as do observations of top-of-atmosphere radiation. Climate model results, including a revised set that is constrained by observations of the ocean heat content evolution show a consistent sign and magnitude for a positive forcing relative to 2000 due to reduced aerosol effects. This reduction leads to an acceleration of the forcing of climate change, i.e. an increase in forcing by 0.1 to 0.3 W m-2, up to 12 % of the total climate forcing in 2019 compared to 1750 according to IPCC.

The regional impacts of multiple possible future emission scenarios can be estimated by combining a few Earth System Model (ESM) simulations with a linear pattern scaling model such as MESMER which uses the pattern of local temperature responses per degree global warming. Here we use MESMER to emulate the future regional pattern of surface temperature response based on historical single-forcer and future Shared Socioeconomic Pathway (SSP) CMIP6 simulations. Pattern scaling errors are decomposed into two components: differences in scaling patterns between scenarios, and intrinsic timeseries differences between local and global responses in the target scenario. The timeseries error is relatively small for high-emissions scenarios, contributing around 20 % of the total error, but is similar in magnitude to the pattern error for lower-emission scenarios. This irreducible timeseries error limits the efficacy of pattern scaling for emulating strong mitigation pathways and reduces the dependence on the predictor pattern used. The results help guide the choice of predictor scenarios and where to target introducing other dependent variables beyond global surface temperature into pattern scaling models.

[H7 O3 ]4 [Tc20 O68 ] ⋅ 4H2 O [1] was prepared from an aqueous Tc2 O7 solution concentrated over anhydrous H2 SO4 . [Tc20 O68 ]4- is the first polyanionic species to be reported for Tc. The unit cell contains one centrosymmetric [Tc20 O68 ]4- polyanion as well as hydronium ions and water molecules. The core of the structure consists of four Tc(V)O6 octahedra that form a square Tc4 O4 ring. The four Tc(V)O6 octahedra are decorated by sixteen Tc(VII)O4 tetrahedra. Calculations show the bonding within the Tc4 O4 ring to consist of a 3-center bond formed between each neighboring pair of Tc atoms and their bridging oxygen. Calculations also indicate that a strong d→d electronic transition at 513 nm is the origin of the red color of [1]. The characterization of red HTcO4 solutions by X-ray absorption spectroscopy has complemented the description of this compound in aqueous solution. The formation mechanisms in solution, including the possible role of technetium's radioactivity in the formation of [1], are discussed.

Remobilization of sedimentary carbonate in subduction zones modulates arc volcanism emissions and thus Earth’s climate over geological timescales. Although limestones (or chalk) are thought to be the major carbon reservoir subducted to subarc depths, their fate is still unclear. Here we present high-pressure reaction experiments between impure limestone (7.4 wt.% clay) and dunite at 1.3–2.7 GPa to constrain the melting behaviour of subducted natural limestone in contact with peridotite. The results show that although clay impurities significantly depress the solidus of limestone, melting will not occur whilst limestones are still part of the subducting slab. Buoyancy calculations suggest that most of these limestones would form solid-state diapirs intruding into the mantle wedge, resulting in limited carbon flux to the deep mantle (< ~10 Mt C y−1). Less than 20% melting within the mantle wedge indicates that most limestones remain stable and are stored in subarc lithosphere, resulting in massive carbon storage in convergent margins considering their high carbon flux (~21.4 Mt C y−1). Assimilation and outgassing of these carbonates during arc magma ascent may dominate the carbon flux in volcanic arcs., Experiments and buoyancy calculations reveal that subduction of limestone results in massive carbon storage in arc lithosphere, forming an important carbon reservoir in convergent margins. Remobilization of this carbon reservoir during arc magma ascent may dominate carbon emissions at volcanic arcs.

Background Brachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose–response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor. Methods Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events, and a probit dose response model was created with maximum likelihood parameter fitting. Results This analysis includes a total of 89 brachial plexus maximum point dose (Dmax) values from both institutions. Among the 14 patients who developed brachial plexopathy, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1–72.2) in the Karolinska dataset, and the Indiana dataset had a median of 13 months (range 1–71). Both studies had a median range of 3 fractions, but in the Indiana dataset, 9 patients were treated in 4 fractions, and the paper did not differentiate between the two, so our analysis is considered to be in 3–4 fractions, one of the main limitations. The probit model showed that the risk of brachial plexopathy with Dmax of 26 Gy in 3–4 fractions is 10%, and 50% with Dmax of 70 Gy in 3–4 fractions. Conclusions This analysis is only a preliminary result because more details are needed as well as additional comprehensive datasets from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

Purpose Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa. Methods and Materials A PubMed search was performed to review the published literature on the use of hypofractionated SBRT (usually in 1-5 fractions) for PCa in various clinical scenarios (eg, preoperative [neoadjuvant], borderline resectable, and locally advanced PCa). The linear quadratic model with α/β= 10 Gy was used to address differences in fractionation. Logistic tumor control probability models were generated using maximum likelihood parameter fitting. Results After converting to 3-fraction equivalent doses, the pooled reported data and associated models suggests that 1-year local control (LC) without surgery is ≈79% to 86% after the equivalent of 30 to 36 Gy in 3 fractions, showing a dose response in the range of 25 to 36 Gy, and decreasing to less than 70% 1-year LC at doses below 24 Gy in 3 fractions. The 33 Gy in 5 fraction regimen (Alliance A021501) corresponds to 28.2 Gy in 3 fractions, for which the HyTEC pooled model had 77% 1-year LC without surgery. Above an equivalent dose of 28 Gy in 3 fractions, with margin-negative resection the 1-year LC exceeded 90%. Conclusions Pooled analyses of reported tumor control probabilities for commonly used SBRT dose-fractionation schedules for PCa suggests a dose response. These findings should be viewed with caution given the challenges and limitations of this review. Additional data are needed to better understand the dose or fractionation-response of SBRT for PCa.

This manuscript adds to the literature of endocrine regulation of adaptive thermogenesis and energy balance. It specifically describes the role of pituitary adenylate cyclase-activating polypeptide on the regulation of brown adipose tissue via the sympathetic nervous system with a focus on compensatory mechanisms of thermogenesis. We highlight sex-specific differences in energy metabolism.

Background: Tenecteplase is a genetically engineered fibrinolytic with growing interest in the treatment of acute ischemic stroke. Compared to alteplase, tenecteplase is effective for neurologic improvement following ischemic stroke in patients with large vessel occlusions who are eligible for thrombectomy and for mild ischemic strokes with National Institutes of Health Stroke Scale of 0 to 5. Objective: The purpose of this study is to determine if safety outcomes are different in patients receiving tenecteplase and alteplase for acute ischemic stroke. Methods: This retrospective cohort reviewed all patients who received alteplase or tenecteplase from January 2019 to December 2020. Patients admitted before April 28, 2020, received alteplase intravenous bolus over 1 minute followed by an infusion over 1 hour, for a total of 0.9 mg/kg. Patients admitted after this date received tenecteplase 0.25 mg/kg as an intravenous bolus over 5 to 10 seconds. Any patient transferring from an outside facility was excluded. The primary outcome was major bleeding. Results: There was no significant difference in major bleeding between alteplase and tenecteplase (40 [18%] vs 21 [18.1%], P = 0.985). There was no significant difference in all-cause inpatient mortality for alteplase versus tenecteplase (10 [5%] vs 5 [4%], P = 0.934) or in adverse events between the groups (22 [9%] vs 14 [12%], P = 0.541) for alteplase and tenecteplase, respectively. Conclusions and Relevance: Tenecteplase had similar rates of major bleeding versus alteplase and may be a reasonable alternative in the treatment of acute ischemic stroke.

Ethylene glycol (EG) toxicity is an important cause of toxic alcohol poisoning in the USA with over 5,000 exposures reported annually. While classically characterized by solitary accidental or intentional ingestions, mass toxic alcohol poisoning outbreaks and more rarely collective consumptions (typically of methanol) have been described. We describe an ethylene glycol poisoning from collective ingestion that involved soldiers presenting at William Beaumont Army Medical Center in El Paso, Texas. Eleven soldiers presented to the emergency department over a 12-h period after ingestion of an unknown substance. The first two patients exhibited severe neurologic symptoms, while the remainder were asymptomatic. As serum EG levels were not immediately available, treatment decisions were based on surrogate laboratory values. Two patients received immediate hemodialysis, and fomepizole (FOM) because of severe acidosis with elevated anion and osmolal gaps. These patients developed acute kidney injury with renal recovery within a 3-week period. Two patients with elevated lactate received bicarbonate-based intravenous (IV) fluids and FOM. Two patients received IV fluids only and required prolonged observation for worsening acidosis and/or acute kidney injury. Five patients with normal laboratory values were treated with IV fluids and observation. All patients received cofactors including thiamine and pyridoxine. All patients survived. The outbreak occurred in the setting of limited dialysis resources, limited FOM availability, and in a resource-limited community. Additional guidelines are needed to determine allocation of limited resources, optimal dialysis and FOM treatment course, and comorbid conditions, which may prolong recovery.

Climate-driven changes to environmental conditions are driving severe declines of coral reef ecosystems. Current climate vulnerability estimates commonly focus on ocean warming and typically overlook ecological responses or use broad proxies to represent responses, leading to management decisions based on incomplete views of coral reef futures. We explore four underdeveloped aspects of climate vulnerability assessments and make the following recommendations: (1) use climate projections based on changes in global warming as future scenarios in place of the more common emissions scenarios; (2) include available high-resolution projections for climate variables in addition to thermal stress; (3) combine projected climate stressors accounting for uncertainty in future outcomes; and (4) quantitatively assess historical and project future ecological sensitivity and adaptive capacity of corals to multiple stressors. We demonstrate how this framework can be used to reduce uncertainty in projected climate vulnerability and facilitate targeted investment in managing reefs most likely to endure climatic disturbances.

We demonstrate the synthesis and phase stability of TcN, Tc2N, and a substoichiometric TcNx from 0 to 50 GPa and to 2500 K in a laser-heated diamond anvil cell. At least potential recoverability is demonstrated for each compound. TcN adopts a previously unpredicted structure identified via crystal structure prediction.

New findings What is the central question of this study? Can chronic treatment of pituitary adenylate cyclase-activating polypeptide (PACAP) deficient mice with the melanocortin agonist melanotan II during cold acclimation rescue the impaired thermogenic capacity previously observed in PACAP deficient mice? What is the main finding and its importance? Using a genetic model of PACAP deficiency, this study provides evidence that PACAP acts upstream of the melanocortin system in regulating sympathetic nerve activity to brown adipose tissue in mice. Abstract Impaired adipose tissue function in obesity, including reduced thermogenic potential, has detrimental consequences for metabolic health. Hormonal regulation of adaptive thermogenesis is being explored as a potential therapeutic target for human obesity. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide expressed in nuclei of the hypothalamus known to regulate energy expenditure, and functional studies reveal a role for PACAP in the central regulation of thermogenesis, although mechanisms are not well understood. We hypothesized that PACAP acts upstream of the melanocortin system to regulate sympathetic nerve activity to stimulate thermogenesis. To assess this, female PACAP-/- and PACAP+/+ mice were given daily peripheral injections of a melanocortin receptor agonist, melanotan II (MTII), for 3 weeks during cold acclimation, and the effect of MTII on thermogenic capacity and adipose tissue remodelling was examined by physiological and histological analyses. MTII partially rescued the impaired thermogenic capacity in PACAP-/- mice as compared to PACAP+/+ mice as determined by measuring noradrenaline-induced metabolic rate. In addition, MTII treatment during cold acclimation corrected the previously identified deficit in lipid utilization in response to adrenergic stimulation in PACAP-/- null mice, suggesting impaired lipid mobilization may contribute to the impaired thermogenic capacity of PACAP-/- mice. Results presented here provide physiological evidence to suggest that PACAP acts upstream of melanocortin receptors to facilitate sympathetically induced mechanisms of adaptive thermogenesis in response to cold acclimation.

Background and aims Field pea production is greatly impacted by multiple soil-borne fungal and oomycete pathogens in a complex. The objectives of this research were to 1) identify the soil-borne pathogens associated with field pea in North Dakota and; 2) develop prediction models incorporating the occurrence of the soil-borne pathogen communities, soil edaphic properties and disease incidence. Methods Soil and plants were sampled from 60 field pea fields in North Dakota during 2014 and 2015. Plants (1500 across two years) were rated for both root rot and soil-borne pathogens isolated from roots. Soils were analyzed for edaphic properties. Indicator species analysis was used to identify soil-borne pathogen communities. Logistic regression was used to determine associations and develop prediction models. Results Survey results from 2014 and 2015 indicated that the most prevalent soil-borne pathogens identified in field pea fields were Fusarium spp. and Aphanomyces euteiches. Five soil-borne pathogen communities were identified; three of which had statistically significant associations characterized by (1) Fusarium acuminatum, (3) A. euteiches, and (4) Fusarium sporotrichioides. The occurrence of the three communities were associated with clay content, soil pH, Fe2+, and K+. Disease incidence was associated with the presence of either community 1 or 3 and K+. Conclusions The results generated from this research will contribute to the development of management strategies by providing a soil-borne pathogen community prediction tool.

Aims Non-renal extravasation of phosphate from the circulation and transient accumulation into tissues and extracellular fluid is a regulated process of acute phosphate homeostasis that is not well understood. This process is especially relevant in the setting of chronic kidney disease (CKD), where exposure to increased phosphate is prolonged due to inefficient kidney excretion. Furthermore, CKD-associated mineral dysregulation induces pathological accumulation of phosphate causing vascular calcification (VC). Our objective was to determine whether the systemic response to acute phosphate challenges is altered by VC. Methods and results After bolus phosphate administration, circulating and tissue deposition of this challenge was assessed in two rat models of VC using a radiolabelled phosphate tracer. In an adenine-induced model of CKD (N = 70), animals with VC had a blunted elevation of circulating 33PO4 following oral phosphate administration (P < 0.01), and the discordant deposition could be traced to the calcified arteries (11.4 [7.5–13.1] vs.43.0 [35.5–53.7] pmol/ng tissue, P < 0.001). In a non-CKD model of VC, calcification was induced with 0.5 ug/kg calcitriol and then withdrawn (N = 24). New phosphate uptake by the calcified vasculature correlated to the pre-existing burden of calcification (r = 38, P < 0.001) and was substantially attenuated in the absence of calcification stimulus (P < 0.01). Phosphate accrual was stimulated by the phosphate challenge and not present to the same degree during passive disposition of circulating phosphate. Further, the form of phosphate that deposited to the vasculature was predominately amorphous inorganic phosphate and not that which was bound in matured calciprotein particles. Conclusions In the process of calcification, arteries acutely deposit substantial amorphous phosphate while blunting the elevation in the circulation, thereby altering the systemic disposition of phosphate and identifying VC as a participatory mineral homeostatic organ. This study demonstrates the negative vascular consequence of acute fluctuations in circulating phosphate, and supports the importance of phosphate bioavailability and diet management in CKD patients as a mediator of cardiovascular risk.