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BACKGROUND: A culture of improvement is an important feature of high-quality health care systems. However, health care teams often need support to translate quality improvement (QI) activities into practice. One method of support is consultation from a QI coach. The literature suggests that coaching interventions have a positive impact on clinical outcomes. However, the impact of coaching on specific process outcomes, like adoption of clinical care activities, is unknown. Identifying the process outcomes for which QI coaching is most effective could provide specific guidance on when to employ this strategy. METHODS: We searched multiple databases from inception through July 2021. Studies that addressed the effects of QI coaching on process of care outcomes were included. Two reviewers independently extracted study characteristics and assessed risk of bias. Certainty of evidence was assessed using GRADE. RESULTS: We identified 1983 articles, of which 23 cluster-randomized trials met eligibility criteria. All but two took place in a primary care setting. Overall, interventions typically targeted multiple simultaneous processes of care activities. We found that coaching probably has a beneficial effect on composite process of care outcomes (n = 9) and ordering of labs and vital signs (n = 6), and possibly has a beneficial effect on changes in organizational process of care (n = 5), appropriate documentation (n = 5), and delivery of appropriate counseling (n = 3). We did not perform meta-analyses because of conceptual heterogeneity around intervention design and outcomes; rather, we synthesized the data narratively. Due to imprecision, inconsistency, and high risk of bias of the included studies, we judged the certainty of these results as low or very low. CONCLUSION: QI coaching interventions may affect certain processes of care activities such as ordering of labs and vital signs. Future research that advances the identification of when QI coaching is most beneficial for health care teams seeking to implement improvement processes in pursuit of high-quality care will support efficient use of QI resources. Protocol Registration. This study was registered and followed a published protocol (PROSPERO: CRD42020165069). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-07217-2.

Background Adjustment disorder (AD) is the most common mental health diagnosis in the U.S. military and is more than twice as likely to be diagnosed in active duty servicewomen as compared with male servicemembers. The literature on ADs, particularly in female servicemembers, has not been reviewed yet. We conducted a scoping review of the literature to explore the degree of research activity and summarize current literature gaps. Methods We created a PRISMA-ScR checklist and prospectively registered it in Open Science Framework. The literature search included articles (including studies and reports) published between 2000 and 2018 in either the grey literature or the following databases: Ovid Medline, CINAHL, Embase, PsycINFO, Web of Science, and Ovid Cochrane. We used DistillerSR to conduct title and abstracts screening, full-text screening, and data charting. The social ecological model for military women's health framework was used to organize the results. Results After screening 1,304 records, 29 were included for data charting. Most frequently, studies were descriptive (cross-sectional) (25%), with no randomized controlled studies. The studies primarily focused on ADs’ risk factors in servicewomen (76%), followed by military readiness (38%). Only 14% addressed recommendations for treatments based on expert opinion, although they did not directly test interventions, and 7% focused on health outcomes. Conclusions ADs affect the health of U.S. military women and military readiness, yet little is known about their successful treatment or health outcomes. Additional research in those areas is warranted.

The pace of Holocene vegetation change Although much is known about the rapid environmental changes that have occurred since the Industrial Revolution, the patterns of change over the preceding millennia have been only patchily understood. Using a global set of >1100 fossil pollen records, Mottl et al. explored the rates of vegetation change over the past 18,000 years (see the Perspective by Overpeck and Breshears). The authors show that the rates of change accelerated markedly during the Late Holocene (∼4.6 to 2.9 thousand years ago), even more rapidly than the climate-driven vegetation changes associated with the end of the last glacial period. In addition, the Late Holocene acceleration began for terrestrial communities as a whole, suggesting that the acceleration in turnover over the past two centuries is the tip of a deeper trend. Science , abg1685, this issue p. 860 ; see also abi9902, p. 786

Background Antimicrobial misuse is common in low-income and middle-income countries (LMICs), and this practice is a driver of antibiotic resistance. We compared community-based antibiotic access and use practices across communities in LMICs to identify contextually specific targets for interventions to improve antibiotic use practices. Methods We did quantitative and qualitative assessments of antibiotic access and use in six LMICs across Africa (Mozambique, Ghana, and South Africa) and Asia (Bangladesh, Vietnam, and Thailand) over a 2·5-year study period (July 1, 2016–Dec 31, 2018). We did quantitative assessments of community antibiotic access and use through supplier mapping, customer exit interviews, and household surveys. These quantitative assessments were triangulated with qualitative drug supplier and consumer interviews and discussions. Findings Vietnam and Bangladesh had the largest proportions of non-licensed antibiotic dispensing points. For mild illness, drug stores were the most common point of contact when seeking antibiotics in most countries, except South Africa and Mozambique, where public facilities were most common. Self-medication with antibiotics was found to be widespread in Vietnam (55·2% of antibiotics dispensed without prescription), Bangladesh (45·7%), and Ghana (36·1%), but less so in Mozambique (8·0%), South Africa (1·2%), and Thailand (3·9%). Self-medication was considered to be less time consuming, cheaper, and overall, more convenient than accessing them through health-care facilities. Factors determining where treatment was sought often involved relevant policies, trust in the supplier and the drug, disease severity, and whether the antibiotic was intended for a child. Confusion regarding how to identify oral antibiotics was revealed in both Africa and Asia. Interpretation Contextual complexities and differences between countries with different incomes, policy frameworks, and cultural norms were revealed. These contextual differences render a single strategy inadequate and instead necessitate context-tailored, integrated intervention packages to improve antibiotic use in LMICs as part of global efforts to combat antibiotic resistance. Funding Wellcome Trust and Volkswagen Foundation.

In order for health care innovations to be effective and actionable, they must align with the needs and practice patterns of those delivering care at the bedside. While research has started to incorporate the patient voice, it has yet to fully invest in the expertise of frontline clinicians. Frontline clinicians carry a wealth of clinical knowledge and the lived experience of providing real-world medical care that the research community seeks to improve. We consider options for clinicians as research stakeholders along a continuum of engagement as outlined by the UCSF Clinical and Translational Science Institute from minimal to supportive to participatory. In order to make an effective value proposition to support reallocation of clinician time to research engagement, we advocate evaluating the impact of clinicians as stakeholders at both the process level (e.g., clinician satisfaction, study recruitment rates) and endpoint level (e.g., clinical outcomes). Investing in clinicians as research stakeholders can offer benefits for the individual, health system, and population by increasing the generalizability, adoption, and sustainability of effective interventions.

Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019–2020 influenza vaccine against influenza-associated hospitalization in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve-transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases vs test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results A total of 3116 participants were included, including 18% (n = 553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (n = 2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI], 27%–52%). VE against A(H1N1)pdm09 viruses was 40% (95% CI, 24%–53%) and 33% against B viruses (95% CI, 0–56%). Of the 2 major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A + 187A,189E) was 59% (95% CI, 34%–75%) whereas no VE was observed against the other group (5A + 156K) (–1% [95% CI, –61% to 37%]). Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

We estimated vaccine effectiveness (VE) for prevention of influenza-associated hospitalizations among adults during the 2018–2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and testing positive for influenza were cases; patients testing negative were controls. VE was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with a mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09–associated hospitalization was 51% (95% confidence interval [CI], 25%–68%). Adjusted VE against influenza A(H3N2) virus–associated hospitalization was −2% (95% CI, −65% to 37%) and differed significantly by age, with VE of −130% (95% CI, −374% to −27%) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza A(H1N1)pdm09–associated hospitalizations, it conferred no protection against influenza A(H3N2)–associated hospitalizations. We observed negative VE for young and middle-aged adults but cannot exclude residual confounding as a potential explanation.

In the southern Great Lakes Region, North America, between 19,000 and 8,000 years ago, temperatures rose by 2.5–6.5°C and spruce Picea forests/woodlands were replaced by mixed‐deciduous or pine Pinus forests. The demise of Picea forests/woodlands during the last deglaciation offers a model system for studying how changing climate and disturbance regimes interact to trigger declines of dominant species and vegetation‐type conversions. The role of rising temperatures in driving the regional demise of Picea forests/woodlands is widely accepted, but the role of fire is poorly understood. We studied the effect of changing fire activity on Picea declines and rates of vegetation composition change using fossil pollen and macroscopic charcoal from five high‐resolution lake sediment records. The decline of Picea forests/woodlands followed two distinct patterns. At two sites (Stotzel‐Leis and Silver Lake), fire activity reached maximum levels during the declines and both charcoal accumulation rates and fire frequency were significantly and positively associated with vegetation composition change rates. At these sites, Picea declined to low levels by 14 kyr BP and was largely replaced by deciduous hardwood taxa like ash Fraxinus, hop‐hornbeam/hornbeam Ostrya/Carpinus and elm Ulmus. However, this ecosystem transition was reversible, as Picea re‐established at lower abundances during the Younger Dryas. At the other three sites, there was no statistical relationship between charcoal accumulation and vegetation composition change rates, though fire frequency was a significant predictor of rates of vegetation change at Appleman Lake and Triangle Lake Bog. At these sites, Picea declined gradually over several thousand years, was replaced by deciduous hardwoods and high levels of Pinus and did not re‐establish during the Younger Dryas. Synthesis. Fire does not appear to have been necessary for the climate‐driven loss of Picea woodlands during the last deglaciation, but increased fire frequency accelerated the decline of Picea in some areas by clearing the way for thermophilous deciduous hardwood taxa. Hence, warming and intensified fire regimes likely interacted in the past to cause abrupt losses of coniferous forests and could again in the coming decades.

Context Crosstalk through receptor ligand interactions at the maternal-fetal interface is impacted by fetal sex. This affects placentation in the first trimester and differences in outcomes. Sexually dimorphic signaling at early stages of placentation are not defined. Objective Investigate the impact of fetal sex on maternal-fetal crosstalk. Design Receptors/ligands at the maternal-fetal surface were identified from sexually dimorphic genes between fetal sexes in the first trimester placenta and defined in each cell type using single-cell RNA-Sequencing (scRNA-Seq). Setting Academic institution. Samples Late first trimester (~10-13 weeks) placenta (fetal) and decidua (maternal) from uncomplicated ongoing pregnancies. Main outcome measures Transcriptomic profiling at tissue and single-cell level; immunohistochemistry of select proteins. Results We identified 91 sexually dimorphic receptor-ligand pairs across the maternal-fetal interface. We examined fetal sex differences in 5 major cell types (trophoblasts, stromal cells, Hofbauer cells, antigen-presenting cells, and endothelial cells). Ligands from the CC family chemokine ligand (CCL) family were most highly representative in females, with their receptors present on the maternal surface. Sexually dimorphic trophoblast transcripts, Mucin-15 (MUC15) and notum, palmitoleoyl-protein carboxylesterase (NOTUM) were also most highly expressed in syncytiotrophoblasts and extra-villous trophoblasts respectively. Gene Ontology (GO) analysis using sexually dimorphic genes in individual cell types identified cytokine mediated signaling pathways to be most representative in female trophoblasts. Upstream analysis demonstrated TGFB1 and estradiol to affect all cell types, but dihydrotestosterone, produced by the male fetus, was an upstream regulator most significant for the trophoblast population. Conclusions Maternal-fetal crosstalk exhibits sexual dimorphism during placentation early in gestation.

This systematic review compares the risk for nephrogenic systemic fibrosis after exposure to newer versus older gadolinium-based contrast agents.

Reconstructions of prehistoric vegetation composition help establish natural baselines, variability, and trajectories of forest dynamics before and during the emergence of intensive anthropogenic land use. Pollen–vegetation models (PVMs) enable such reconstructions from fossil pollen assemblages using process-based representations of taxon-specific pollen production and dispersal. However, several PVMs and variants now exist, and the sensitivity of vegetation inferences to PVM selection, variant, and calibration domain is poorly understood. Here, we compare the reconstructions, parameter estimates, and structure of a Bayesian hierarchical PVM, STEPPS, both to observations and to REVEALS, a widely used PVM, for the pre–Euro-American settlement-era vegetation in the northeastern United States (NEUS). We also compare NEUS-based STEPPS parameter estimates to those for the upper midwestern United States (UMW). Both PVMs predict the observed macroscale patterns of vegetation composition in the NEUS; however, reconstructions of minor taxa are less accurate and predictions for some taxa differ between PVMs. These differences can be attributed to intermodel differences in structure and parameter estimates. Estimates of pollen productivity from STEPPS broadly agree with estimates produced for use in REVEALS, while comparison between pollen dispersal parameter estimates shows no significant relationship. STEPPS parameter estimates are similar between the UMW and NEUS, suggesting that STEPPS parameter estimates are transferable between floristically similar regions and scales.

Two usages of ‘climate sensitivity’ co-exist: one climatological and one ecological. The earlier climatological usage quantifies the sensitivity of global mean surface temperature to atmospheric CO2, with formal variants differing by timescale and processes. The ecological usage, renamed here as ecoclimate sensitivity, is defined as a change in an ecological response variable per unit climate change. The two concepts are treated very differently: climatologists have focused on reducing uncertainty of global climate sensitivity estimates, while ecologists have focused on the multivariate processes governing variations in ecoclimate sensitivity across drivers, response variables, and scales. Because radiative forcing scales logarithmically to [CO2]atm, ecological impacts per ppm [CO2]atm often also scale logarithmically, although non-linear ecoclimate sensitivities can alter this expectation. Critically, past estimates of climate and ecoclimate sensitivity carry an implicit tradeoff, in which smaller estimates of climate sensitivity indicate higher ecoclimate sensitivities. For the LGM, estimates of equilibrium climate sensitivity have narrowed to 2.4 to 4.5 °C, while high ecoclimate sensitivity is indicated by post-glacial biome conversions, continental-scale species range shifts, and high community turnover. We introduce a new term, ecocarbon sensitivity, defined as the product of global climate sensitivity, local ecoclimate sensitivity, and a global-to-local climate scaling factor. Given past biospheric transformations, we can expect high sensitivity of the terrestrial biosphere to current rises in [CO2]atm, a conclusion that is insensitive to estimates of climate sensitivity. The next frontier is better quantification of the processes governing the form and variations of ecoclimate and ecocarbon sensitivity across systems and scales.

The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the role of colonoscopy for diagnostic evaluation of colorectal cancer (CRC) after a presumed diagnosis of acute left-sided colonic diverticulitis and on the role of pharmacologic, nonpharmacologic, and elective surgical interventions to prevent recurrence after initial treatment of acute complicated and uncomplicated left-sided colonic diverticulitis. This guideline is based on the current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences.The ACP Clinical Guidelines Committee (CGC) based these recommendations on a systematic review on the role of colonoscopy after acute left-sided colonic diverticulitis and pharmacologic, nonpharmacologic, and elective surgical interventions after initial treatment. The systematic review evaluated outcomes rated by the CGC as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method.The target audience is all clinicians, and the target patient population is adults with recent episodes of acute left-sided colonic diverticulitis.

The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the diagnosis and management of acute left-sided colonic diverticulitis in adults. This guideline is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences.The ACP Clinical Guidelines Committee (CGC) developed this guideline based on a systematic review on the use of computed tomography (CT) for the diagnosis of acute left-sided colonic diverticulitis and on management via hospitalization, antibiotic use, and interventional percutaneous abscess drainage. The systematic review evaluated outcomes that the CGC rated as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology.The target audience is all clinicians, and the target patient population is adults with suspected or known acute left-sided colonic diverticulitis.

Healthcare organisations and teams perform improvement activities to facilitate high-quality healthcare. The use of an improvement coach who provides support and guidance to the healthcare team may facilitate improvement activities; however, no systematic review exists on the facilitators and barriers to implementing an improvement coach.We conducted a qualitative evidence synthesis to examine the facilitators and barriers to the implementation of improvement coaching.We searched MEDLINENineteen studies with a qualitative component met the inclusion criteria. Four themes of barriers and facilitators crossed multiple CFIR domains: adaptability (e.g. making adjustments to the project; process, or approach); knowledge and skills (e.g. understanding of content and process for the project); engagement (e.g. willingness to be involved in the process) and resources (e.g. assets required to complete the improvement process).Improvement coaching is a complex intervention that influences the context, healthcare team being coached and improvement activities. Improvement coaches should understand how to minimise barriers and promote facilitators that are unique to each improvement project across the domains. Limitations of the study are related to the nature of the intervention including potential publication bias given quality improvement focus; the variety of terms similar to improvement coaching or selection of framework.

BACKGROUND: Technology-based systems can facilitate remote decision-making to triage patients to the appropriate level of care. Despite technologic advances, the effects of implementation of these systems on patient and utilization outcomes are unclear. We evaluated the effects of remote triage systems on healthcare utilization, case resolution, and patient safety outcomes. METHODS: English-language searches of MEDLINE (via PubMed), EMBASE, and CINAHL were performed from inception until July 2018. Randomized and nonrandomized comparative studies of remote triage services that reported healthcare utilization, case resolution, and patient safety outcomes were included. Two reviewers assessed study and intervention characteristics independently for study quality, strength of evidence, and risk of bias. RESULTS: The literature search identified 5026 articles, of which eight met eligibility criteria. Five randomized, two controlled before-and-after, and one interrupted time series study assessed 3 categories of remote triage services: mode of delivery, triage professional type, and system organizational level. No study evaluated any other delivery mode other than telephone and in-person. Meta-analyses were unable to be performed because of study design and outcome heterogeneity; therefore, we narratively synthesized data. Overall, most studies did not demonstrate a decrease in primary care (PC) or emergency department (ED) utilization, with some studies showing a significant increase. Evidence suggested local, practice-based triage systems have greater case resolution and refer fewer patients to PC or ED services than regional/national systems. No study identified statistically significant differences in safety outcomes. CONCLUSION: Our review found limited evidence that remote triage reduces the burden of PC or ED utilization. However, remote triage by telephone can produce a high rate of call resolution and appears to be safe. Further study of other remote triage modalities is needed to realize the promise of remote triage services in optimizing healthcare outcomes. PROTOCOL REGISTRATION: This study was registered and followed a published protocol (PROSPERO: CRD42019112262). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05585-4) contains supplementary material, which is available to authorized users.

We test several quantitative algorithms as palaeoclimate reconstruction tools for North American and European fossil pollen data, using both classical methods and newer machine-learning approaches based on regression tree ensembles and artificial neural networks. We focus on the reconstruction of secondary climate variables (here, January temperature and annual water balance), as their comparatively small ecological influence compared to the primary variable (July temperature) presents special challenges to palaeo-reconstructions. We test the pollen–climate models using a novel and comprehensive cross-validation approach, running a series of h-block cross-validations using h values of 100–1500 km. Our study illustrates major benefits of this variable h-block cross-validation scheme, as the effect of spatial autocorrelation is minimized, while the cross-validations with increasing h values can reveal instabilities in the calibration model and approximate challenges faced in palaeo-reconstructions with poor modern analogues. We achieve well-performing calibration models for both primary and secondary climate variables, with boosted regression trees providing the overall most robust performance, while the palaeoclimate reconstructions from fossil datasets show major independent features for the primary and secondary variables. Our results suggest that with careful variable selection and consideration of ecological processes, robust reconstruction of both primary and secondary climate variables is possible.

Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (20 ng/mL) and the incidence of bone metastases detected by total-body 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging (n = 93/388, 24%), biochemical recurrence (BCR) localization (n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy (n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (

Objectives The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group defines patient values and preferences as the relative importance patients place on the main health outcomes. We provide GRADE guidance for assessing the risk of bias and indirectness domains for certainty of evidence about the relative importance of outcomes. Study Design and Setting We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance and consulted GRADE members and other stakeholders for feedback. Results This is the first of two articles. A body of evidence addressing the importance of outcomes starts at “high certainty”; concerns with risk of bias, indirectness, inconsistency, imprecision, and publication bias lead to downgrading to moderate, low, or very low certainty. We propose subdomains of risk of bias as selection of the study population, missing data, the type of measurement instrument, and confounding; we have developed items for each subdomain. The population, intervention, comparison, and outcome elements associated with the evidence determine the degree of indirectness. Conclusion This article provides guidance and examples for rating the risk of bias and indirectness for a body of evidence summarizing the importance of outcomes.

Background Spontaneous intracranial hypotension (SIH) is a debilitating disorder caused by non-iatrogenic spinal cerebrospinal fluid leaks. SIH is increasingly recognized as an important treatable cause of secondary headaches. Treatment involves either epidural blood patching or surgery, which have considerable differences in their adverse event rates, recovery times, and cost. The objective of this evidence map is to understand the breadth of studies that investigate SIH treatment efficacy and to identify knowledge gaps to inform future research. Methods This review will consider experimental, observational, and systematic review studies that assess the efficacy of epidural blood patching and surgery for the treatment of patients with SIH. Individual case studies, clinical guidelines, editorials, protocols, and studies that do not assess an intervention will not be included. English language studies will be included without limitation based on the date of publication. Databases to be searched include MEDLINE® (via Ovid), EMBASE (via Elsevier), and Web of Science™ (via Clarivate). Study selection will be performed independently by two investigators with extracted data to include study type, the number of patients included, patient descriptors, intervention characteristics, and outcome measure used. Data will be presented through a narrative summary aided by tabular and graphical formats in a manner that aligns with the objective of the evidence mapping review. Discussion The overarching goal of this evidence map is to provide an improved understanding of the breadth of studies investigating SIH treatment efficacy in the literature and to thereby identify knowledge gaps that can inform future research directions. Trial registration OSF Registry https://osf.io/nwju7.

Background In low- and middle-income countries (LMICs), the continuum of care (CoC) for maternal, newborn, and child health (MNCH) is not always complete. This study aimed to evaluate the effectiveness of an integrated package of CoC interventions on the CoC completion, morbidity, and mortality outcomes of woman–child pairs in Ghana. Methods and findings This cluster-randomized controlled trial (ISRCTN: 90618993) was conducted at 3 Health and Demographic Surveillance System (HDSS) sites in Ghana. The primary outcome was CoC completion by a woman–child pair, defined as receiving antenatal care (ANC) 4 times or more, delivery assistance from a skilled birth attendant (SBA), and postnatal care (PNC) 3 times or more. Other outcomes were the morbidity and mortality of women and children. Women received a package of interventions and routine services at health facilities (October 2014 to December 2015). The package comprised providing a CoC card for women, CoC orientation for health workers, and offering women with 24-hour stay at a health facility or a home visit within 48 hours after delivery. In the control arm, women received routine services only. Eligibility criteria were as follows: women who gave birth or had a stillbirth from September 1, 2012 to September 30, 2014 (before the trial period), from October 1, 2014 to December 31, 2015 (during the trial period), or from January 1, 2016 to December 31, 2016 (after the trial period). Health service and morbidity outcomes were assessed before and during the trial periods through face-to-face interviews. Mortality was assessed using demographic surveillance data for the 3 periods above. Mixed-effects logistic regression models were used to evaluate the effectiveness as difference in differences (DiD). For health service and morbidity outcomes, 2,970 woman–child pairs were assessed: 1,480 from the baseline survey and 1,490 from the follow-up survey. Additionally, 33,819 cases were assessed for perinatal mortality, 33,322 for neonatal mortality, and 39,205 for maternal mortality. The intervention arm had higher proportions of completed CoC (410/870 [47.1%]) than the control arm (246/620 [39.7%]; adjusted odds ratio [AOR] for DiD = 1.77; 95% confidence interval [CI]: 1.08 to 2.92; p = 0.024). Maternal complications that required hospitalization during pregnancy were lower in the intervention (95/870 [10.9%]) than in the control arm (83/620 [13.4%]) (AOR for DiD = 0.49; 95% CI: 0.29 to 0.83; p = 0.008). Maternal mortality was 8/6,163 live births (intervention arm) and 4/4,068 live births during the trial period (AOR for DiD = 1.60; 95% CI: 0.40 to 6.34; p = 0.507) and 1/4,626 (intervention arm) and 9/3,937 (control arm) after the trial period (AOR for DiD = 0.11; 95% CI: 0.11 to 1.00; p = 0.050). Perinatal and neonatal mortality was not significantly reduced. As this study was conducted in a real-world setting, possible limitations included differences in the type and scale of health facilities and the size of subdistricts, contamination for intervention effectiveness due to the geographic proximity of the arms, and insufficient number of cases for the mortality assessment. Conclusions This study found that an integrated package of CoC interventions increased CoC completion and decreased maternal complications requiring hospitalization during pregnancy and maternal mortality after the trial period. It did not find evidence of reduced perinatal and neonatal mortality. Trial registration The study protocol was registered in the International Standard Randomised Controlled Trial Number Registry (90618993)., Akira Shibanuma and co-workers study a package of maternal and child health interventions in a cluster-randomized trial done in Ghana., Author summary Why was this study done? High individual coverages of antenatal care (ANC), delivery assistance from a skilled birth attendant (SBA), and postnatal care (PNC) do not mean that woman–child pairs receive all these services along the continuum of care (CoC) in maternal, newborn, and child health (MNCH). To our knowledge, no previous study has evaluated the effectiveness of interventions on CoC completion (or receiving all the key services along the CoC) under a real-world setting. What did the researchers do and find? We conducted a cluster-randomized controlled trial to evaluate the effectiveness of an integrated package of CoC interventions in a variety of healthcare settings and health facilities at 3 Health and Demographic Surveillance System (HDSS) sites in Ghana. An integrated package of interventions that aimed at enhancing CoC in MNCH increased CoC completion and decreased maternal complications requiring hospitalization during pregnancy. It also reduced maternal mortality after the trial period, although evidence of decreasing perinatal and neonatal mortality was not found. We found strong spillover of intervention effectiveness among mothers and children living in subdistricts in the control arm. What do these findings mean? CoC completion among mothers and children can be improved through a package of interventions combining the use of inexpensive home-based records, orientation for health workers, and encouragement for retention to postpartum care under a real-world setting. CoC completion can be accelerated through better health systems components, such as more community-based health services and upgrading human resources for the health sector.

Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be the result of sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing was used to identify miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n=113) and parturition (n=47). Sequencing and differential expression (DE) analysis identified 432 mature miRNAs expressed in the first trimester female, 425 in the first trimester male, 400 in the third trimester female, and 508 in the third trimester male placenta (baseMean >10). Of these, 11 sexually dimorphic (FDR10) miRNAs were identified in the first and 4 miRNAs were identified in the third trimester, including miR-361-5p, significant in both trimesters, all upregulated in females. Across gestation, 207 miRNAs were DE across gestation, common to both females and males, miR-4483, the most DE across gestation. There were twice as many female-specific differences across gestation as male-specific (44 miRNAs vs 21 miRNAs), indicating that miRNA abundance across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex independent and sex specific placenta miRNA atlas across gestation which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences.Summary SentenceSex dimorphism in miRNA expression is more pronounced in first compared to third trimester placenta, and there are twice as many female-specific gestational differences, indicating miRNA abundance across human gestation is also sexually dimorphic.

Description The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of point-of-care ultrasonography (POCUS) in patients with acute dyspnea in emergency department (ED) or inpatient settings to improve the diagnostic, treatment, and health outcomes of those with suspected congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax. Methods The ACP Clinical Guidelines Committee based this guideline on a systematic review on the benefits, harms, and diagnostic test accuracy of POCUS; patient values and preferences; and costs of POCUS. The systematic review evaluated health outcomes, diagnostic timeliness, treatment decisions, and test accuracy. The critical health, diagnostic, and treatment outcomes evaluated were in-hospital mortality, time to diagnosis, and time to treatment. The important outcomes evaluated were intensive care unit admissions, correctness of diagnosis, disease-specific outcomes, hospital readmissions, length of hospital stay, and quality of life. The critical test accuracy outcomes included false-positive results for suspected pneumonia, pneumothorax, and pulmonary embolism and false-negative results for suspected congestive heart failure, pneumonia, pneumothorax, and pulmonary embolism. Important test accuracy outcomes included false-positive results for suspected congestive heart failure and false-negative and false-positive results for suspected pleural effusion. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Target audience and patient population The target audience is all clinicians, and the target patient population is adult patients with acute dyspnea in ED or inpatient settings. Recommendation ACP suggests that clinicians may use point-of-care ultrasonography in addition to the standard diagnostic pathway when there is diagnostic uncertainty in patients with acute dyspnea in emergency department or inpatient settings (conditional recommendation; low-certainty evidence).

The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of high-flow nasal oxygen (HFNO) in hospitalized patients for initial or postextubation management of acute respiratory failure. It is based on the best available evidence on the benefits and harms of HFNO, taken in the context of costs and patient values and preferences.The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of HFNO. The patient-centered health outcomes evaluated included all-cause mortality, hospital length of stay, 30-day hospital readmissions, hospital-acquired pneumonia, days of intubation or reintubation, intensive care unit (ICU) admission and ICU transfers, patient comfort, dyspnea, delirium, barotrauma, compromised nutrition, gastric dysfunction, functional independence at discharge, discharge disposition, and skin breakdown. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method.The target audience is all clinicians, and the target patient population is adult patients with acute respiratory failure treated in a hospital setting (including emergency departments, hospital wards, intermediate or step-down units, and ICUs).

Rationale: There is an urgent need to understand the risk of viral transmission during nebulizer treatment of patients with coronavirus disease 2019 (COVID-19). Objectives: To assess the risk of transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS, Middle East respiratory syndrome (MERS), and influenza with administration of drugs via nebulizer. Methods: We searched multiple electronic databases, including PubMed(®), China National Knowledge Infrastructure, Wanfang, preprint databases, and clinicaltrials.gov through December 1, 2020. Any study design in any language describing the risk of viral transmission with nebulizer treatment was eligible. Data were abstracted by one investigator and verified by a second. Results: We identified 22 articles: 1 systematic review, 7 cohort/case-control studies, 7 case series, and 7 simulation-based studies. Eight individual studies involved patients with SARS, five involved MERS, and one involved SARS-CoV-2. The seven cohort/case-control studies (four high risk of bias [ROB], three unclear ROB) found mixed results (median odds ratio 3.91, range 0.08–20.67) based on very weak data among a small number of health care workers (HCWs) with variable use of personal protective equipment (PPE). Case series had multiple potential contributors to transmission. Simulation studies found evidence for droplet dispersion after saline nebulization and measureable influenza viral particles up to 1.7 m from the source after 10 minutes of nebulization with a patient simulator. Study heterogeneity prevented meta-analysis. Conclusions: Case series raise concern of transmission risk, and simulation studies demonstrate droplet dispersion with virus recovery, but specific evidence that exposure to nebulizer treatment increases transmission of coronaviruses similar to COVID-19 is inconclusive. Tradeoffs balancing HCW safety and patient appropriateness can potentially minimize risk, including choice of delivery method for inhaled medications (e.g., nebulizer vs. metered dose inhaler) and PPE (e.g., N95 vs. surgical mask).

The number and extent of ancient DNA records from sedimentary environments (sedaDNA) is rapidly increasing, which creates new opportunities for integrative and macroscale investigations into past population, community, and environmental dynamics at unprecedented taxonomic resolution and spatiotemporal extent. However, fully achieving this potential requires a robust cyberinfrastructure that supports the joint analysis of many sedaDNA records with each other and with genomic reference libraries, the latest geochronological controls and age-depth models, complementary paleoecological and paleoenvironmental proxies, and the most recent and updated DNA reference library for taxonomic identifications. Any cyberinfrastructure for macroscale data synthesis must address the variety of ancient DNA records (e.g. taxonomic groups, analytical approaches, depositional contexts) and leverage existing resources and standards such as the Neotoma Paleoecology Database, the MGnify and MG-RAST resources for environmental genomics, and the MixS standard for genetic sequences. In response, a Cyberinfrastructure for Ancient Sedimentary DNA working group has been meeting regularly since summer 2020 to assess the current state of science and informatics, assess needs and gaps, and establish recommendations for next steps forward. An initial survey found over 420 sites worldwide with published or in-development sedaDNA records, with greatest densities in Eurasia. Metabarcoding records, including Amplicon Sequence Variant data and derived taxonomic inferences, are a top priority for trial uploads to Neotoma, with pilot uploads underway, because of the relatively small dataset volumes, the widespread application of metabarcoding assays, and potential of integrating these records with other paleoecological data holdings in Neotoma and linked paleodata resources such as Linked Earth and paleoclimatic data at NOAA’s National Centers for Environmental Informatics. Because taxonomic inferences are heavily conditioned by choice of bioinformatics pipeline and reference databases, a major unmet need is a repository for minimally processed output from raw sequences. In general, no existing genomics or paleoecological resource meets all needs of the sedaDNA community, although each covers key elements, so there is a good potential of advancing macroscale data syntheses by leveraging and linking existing resources.

Data sharing between laboratories is critical for building repeatable, comparable, and robust geochronology and geochemistry workflows. Meanwhile, in the broader geosciences, there is an increasing need for standardized access to aggregated geochemical data tied to basic geological context. Such data can be used to enrich sample and geochemical data repositories (e.g., EarthChem, Geochron.org, publisher archives), align geochemical context with other datasets that capture global change (e.g., Neotoma, the Paleobiology Database), and calibrate digital Earth models (e.g., Macrostrat) against geochronology-driven assessments of geologic time.A typical geochemical lab manages a large archive of interpreted data; standardizing and contributing data products to community-level archives entails significant manual work that is not usually undertaken. Furthermore, without widely accepted interchange formats, this effort must be repeated for each intended destination.Sparrow (https://sparrow-data.org), in development by a consortium of geochronology labs, is a standardized system designed to support labs’ efforts to manage, contextualize, and share their geochemical data. The system augments existing analytical workflows with tools to manage metadata (e.g., projects, sample context, embargo status) and software interfaces for automated data exchange with community facilities. It is extensible for a wide variety of geochemical methods and analytical processes.In this update, we will report on the implementation of Sparrow in the Arizona Laserchron Center detrital zircon facility, and how that lab is using the system to capture geological context across its data archive. We will review similar integrations underway with U-Pb, 40Ar/39Ar, SIMS, optically stimulated luminescence, thermochronology, and cosmogenic nuclide dating. We will also discuss preliminary efforts to aggregate the output of multiple chronometers to refine age calibrations for the Macrostrat stratigraphic model.

ObjectiveTo assess respectful maternity care (RMC) in health facilities.DesignCross-sectional study.SettingForty-three (43) facilities across 15 districts in Bangladesh, 16 in Ghana and 12 in Tanzania.ParticipantsFacility managers; 325 providers (nurses/midwives/doctors)—Bangladesh (158), Ghana (86) and Tanzania (81); and 849 recently delivered women—Bangladesh (295), Ghana (381) and Tanzania (173)—were interviewed. Observation of 641 client–provider interactions was conducted—Bangladesh (387), Ghana (134) and Tanzania (120).AssessmentTrained social scientists and clinicians assessed infrastructure, policies, provision and women’s experiences of RMC (emotional support, respectful care and communication).Primary outcomeRMC provided and/or experienced by women.ResultsThree (20%) facilities in Bangladesh, four (25%) in Ghana and three (25%) in Tanzania had no maternity clients’ toilets and one-half had no handwashing facilities. Policies for RMC such as identification of client abuses were available: 81% (Ghana), 73% (Bangladesh) and 50% (Tanzania), but response was poor. Ninety-four (60%) Bangladeshi, 26 (30%) Ghanaian and 20 (25%) Tanzanian providers were not RMC trained. They provided emotional support during labour care to 107 (80%) women in Ghana, 95 (79%) in Tanzania and 188 (48.5%) in Bangladesh, and were often courteous with them—236 (61%) in Bangladesh, 119 (89%) in Ghana and 108 (90%) in Tanzania. Due to structural challenges, 169 (44%) women in Bangladesh, 49 (36%) in Ghana and 77 (64%) in Tanzania had no privacy during labour. Care was refused to 13 (11%) Tanzanian and 2 Bangladeshi women who could not pay illegal charges. Twenty-five (7%) women in Ghana, nine (6%) in Bangladesh and eight (5%) in Tanzania were verbally abused during care. Providers in all countries highly rated their care provision (95%–100%), and 287 (97%) of Bangladeshi women, 368 (97%) Ghanaians and 152 (88%) Tanzanians reported ‘satisfaction’ with the care they received. However, based on their facility experiences, significant (pConclusionsFacilities in Bangladesh, Ghana and Tanzania have foundational systems that facilitate RMC. Structural inadequacies and policy gaps pose challenges. Many women were, however, unwilling to return to the same facilities for future deliveries although they (and providers) highly rated these facilities.

We present gridded 8 km-resolution data products of the estimated stem density, basal area, and biomass of tree taxa at Euro-American settlement of the midwestern United States during the middle to late 19th century for the states of Minnesota, Wisconsin, Michigan, Illinois, and Indiana. The data come from settlement-era Public Land Survey (PLS) data (ca. 0.8-km resolution) of trees recorded by land surveyors. The surveyor notes have been transcribed, cleaned, and processed to estimate stem density, basal area, and biomass at individual points. The point-level data are aggregated within 8 km grid cells and smoothed using a generalized additive statistical model that accounts for zero-inflated continuous data and provides approximate Bayesian uncertainty estimates. The statistical modeling smooths out sharp spatial features (likely arising from statistical noise) within areas smaller than about 200 km2. Based on this modeling, presettlement Midwestern landscapes supported multiple dominant species, vegetation types, forest types, and ecological formations. The prairies, oak savannas, and forests each had distinctive structures and spatial distributions across the domain. Forest structure varied from savanna (averaging 27 Mg/ha biomass) to northern hardwood (104 Mg/ha) and mesic southern forests (211 Mg/ha). The presettlement forests were neither unbroken and massively-statured nor dominated by young forests constantly structured by broad-scale disturbances such as fire, drought, insect outbreaks, or hurricanes. Most forests were structurally between modern second growth and old growth. We expect the data product to be useful as a baseline for investigating how forest ecosystems have changed in response to the last several centuries of climate change and intensive Euro-American land use and as a calibration dataset for paleoecological proxy-based reconstructions of forest composition and structure for earlier time periods. The data products (including raw and smoothed estimates at the 8-km scale) are available at the LTER Network Data Portal as version 1.0.

The geological record shows that abrupt changes in the Earth system can occur on timescales short enough to challenge the capacity of human societies to adapt to environmental pressures. In many cases, abrupt changes arise from slow changes in one component of the Earth system that eventually pass a critical threshold, or tipping point, after which impacts cascade through coupled climate–ecological–social systems. The chance of detecting abrupt changes and tipping points increases with the length of observations. The geological record provides the only long-term information we have on the conditions and processes that can drive physical, ecological and social systems into new states or organizational structures that may be irreversible within human time frames. Here, we use well-documented abrupt changes of the past 30 kyr to illustrate how their impacts cascade through the Earth system. We review useful indicators of upcoming abrupt changes, or early warning signals, and provide a perspective on the contributions of palaeoclimate science to the understanding of abrupt changes in the Earth system. A synthesis of intervals of rapid climatic change evident in the geological record reveals some of the Earth system processes and tipping points that could lead to similar events in the future.