Late Cretaceous bird from Madagascar reveals unique development of beaks.

Mesozoic birds display considerable diversity in size, flight adaptations and feather organization1-4, but exhibit relatively conserved patterns of beak shape and development5-7. Although Neornithine (that is, crown group) birds also exhibit constraint on facial development8,9, they have comparatively diverse beak morphologies associated with a range of feeding and behavioural ecologies, in contrast to Mesozoic birds. Here we describe a crow-sized stem bird, Falcatakely forsterae gen. et sp. nov., from the Late Cretaceous epoch of Madagascar that possesses a long and deep rostrum, an expression of beak morphology that was previously unknown among Mesozoic birds and is superficially similar to that of a variety of crown-group birds (for example, toucans). The rostrum of Falcatakely is composed of an expansive edentulous maxilla and a small tooth-bearing premaxilla. Morphometric analyses of individual bony elements and three-dimensional rostrum shape reveal the development of a neornithine-like facial anatomy despite the retention of a maxilla-premaxilla organization that is similar to that of nonavialan theropods. The patterning and increased height of the rostrum in Falcatakely reveals a degree of developmental lability and increased morphological disparity that was previously unknown in early branching avialans. Expression of this phenotype (and presumed ecology) in a stem bird underscores that consolidation to the neornithine-like, premaxilla-dominated rostrum was not an evolutionary prerequisite for beak enlargement.

The Evolutionary Transition of the RNA World to Obcells to Cellular-Based Life.

The obcell hypothesis is a proposed route for the RNA world to develop into a primitive cellular one. It posits that this transition began with the emergence of the proto-ribosome which enabled RNA to colonise the external surface of lipids by the synthesis of amphipathic peptidyl-RNAs. The obcell hypothesis also posits that the emergence of a predation-based ecosystem provided a selection mechanism for continued sophistication amongst early life forms. Here, I argue for this hypothesis owing to its significant explanatory power; it offers a rationale why a ribosome which initially was capable only of producing short non-coded peptides was advantageous and it forgoes issues related to maintaining a replicating RNA inside a lipid enclosure. I develop this model by proposing that the evolutionary selection for improved membrane anchors resulted in the emergence of primitive membrane pores which enabled obcells to gradually evolve into a cellular morphology. Moreover, I introduce a model of obcell production which advances that tRNAs developed from primers of the RNA world.

Progress Toward Rubella and Congenital Rubella Syndrome Elimination - Worldwide, 2012-2022.

Rubella virus is a leading cause of vaccine-preventable birth defects. Infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects, including cataracts, deafness, heart defects, and developmental delay, known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine can provide lifelong protection against rubella. The Global Vaccine Action Plan 2011-2020 included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions by 2020, and rubella elimination is a critical goal of the Immunization Agenda 2030. This report updates a previous report and describes progress toward rubella and CRS elimination during 2012-2022. During 2012-2022, among 194 WHO countries, the number that included rubella-containing vaccine (RCV) in their immunization schedules increased from 132 (68%) to 175 (90%) and the percentage of the world's infants vaccinated against rubella increased from 40% to 68%. Reported rubella cases declined 81%, from 93,816 in 2012 to 17,407 in 2022. Verification of rubella elimination was achieved in 98 (51%) of 194 countries by 2022, an increase from 84 (43%) countries in 2019. Despite significant progress in the introduction of RCV into routine immunization programs worldwide, approximately 25 million infants annually still do not have access to RCV. Nevertheless, even in complex settings, the increasing number of countries that have achieved and sustained rubella elimination demonstrates progress toward global rubella elimination.

Progress Toward Measles Elimination - World Health Organization Eastern Mediterranean Region, 2019-2022.

In 2015, all 22 World Health Organization Eastern Mediterranean Region (EMR) countries and areas (countries) pledged to achieve measles elimination by 2020. Despite success in several countries, most countries in the region still have not eliminated measles. This report updates a previous report and describes progress toward measles elimination in EMR during 2019-2022. During that period, estimated regional coverage with the first and second doses of a measles-containing vaccine (MCV) was 82%-83% and 76%-78%, respectively. During 2019-2022, approximately 160 million children were vaccinated during national or subnational supplementary immunization activities. Reported confirmed regional measles incidence decreased from 29.8 cases per 1 million population in 2019 to 7.4 in 2020, but then increased 68%, to 50.0 in 2022 because of challenges providing immunization services and conducting surveillance during the COVID-19 pandemic. Surveillance indicators deteriorated in 11 (50%) of the 22 EMR countries. During 2019-2022, four countries in the region were verified as having achieved measles elimination, but other countries reported immunity gaps and increased measles incidence in 2022. To achieve measles elimination in EMR, national immunization programs, especially in those countries with high measles incidence, will need to continue to recover from the COVID-19 pandemic, increase overall vaccination coverage to close immunity gaps, and maintain high-quality disease surveillance.

AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation.

In addition to acting as template for protein synthesis, messenger RNA (mRNA) often contains sensory sequence elements that regulate this process. Here we report a new mechanism that limits the number of complete protein molecules that can be synthesized from a single mRNA molecule of the human AMD1 gene encoding adenosylmethionine decarboxylase 1 (AdoMetDC). A small proportion of ribosomes translating AMD1 mRNA stochastically read through the stop codon of the main coding region. These readthrough ribosomes then stall close to the next in-frame stop codon, eventually forming a ribosome queue, the length of which is proportional to the number of AdoMetDC molecules that were synthesized from the same AMD1 mRNA. Once the entire spacer region between the two stop codons is filled with queueing ribosomes, the queue impinges upon the main AMD1 coding region halting its translation. Phylogenetic analysis suggests that this mechanism is highly conserved in vertebrates and existed in their common ancestor. We propose that this mechanism is used to count and limit the number of protein molecules that can be synthesized from a single mRNA template. It could serve to safeguard from dysregulated translation that may occur owing to errors in transcription or mRNA damage.

Evaluating data integrity in ribosome footprinting datasets through modelled polysome profiles.

The assessment of transcriptome-wide ribosome binding to mRNAs is useful for studying the dynamic regulation of protein synthesis. Two methods frequently applied in eukaryotic cells that operate at different levels of resolution are polysome profiling, which reveals the distribution of ribosome loads across the transcriptome, and ribosome footprinting (also termed ribosome profiling or Ribo-Seq), which when combined with appropriate data on mRNA expression can reveal ribosome densities on individual transcripts. In this study we develop methods for relating the information content of these two methods to one another, by reconstructing theoretical polysome profiles from ribosome footprinting data. Our results validate both approaches as experimental tools. Although we show that both methods can yield highly consistent data, some published ribosome footprinting datasets give rise to reconstructed polysome profiles with non-physiological features. We trace these aberrant features to inconsistencies in RNA and Ribo-Seq data when compared to datasets yielding physiological polysome profiles, thereby demonstrating that modelled polysomes are useful for assessing global dataset properties such as its quality in a simple, visual approach. Aside from using polysome profile reconstructions on published datasets, we propose that this also provides a useful tool for validating new ribosome footprinting datasets in early stages of analyses.

Carbonservation with Demonstrated Biodiversity and Carbon Gains: Carbon Can Pay But Biodiversity Must Lead.

Land use has a critical role to play in both climate change mitigation and biodiversity conservation, and increasingly there have been calls to integrate policies for concurrently meeting Paris Agreement commitments and the UN decade on ecosystem restoration 2021-2030. Currently however, investment activities have been dominated by climate change mitigation activities, including through the development of carbon markets (both voluntary and compliance markets). Whilst climate change mitigation is to be welcomed, the prioritization of carbon in avoided deforestation and reforestation can lead to suboptimal or negative outcomes for biodiversity. Restoration of degraded native vegetation may provide an opportunity for concurrent production of both carbon and biodiversity benefits, by harnessing existing carbon markets without the need to trade-off biodiversity outcomes. Here we demonstrate that carbon sequestered by restoring degraded temperate woodland can pay the price of the restored biodiversity. This is shown using conservative carbon prices in an established market (during both a voluntary and compliance market phase), and the restoration price revealed by a 10-year conservation incentive payment scheme. When recovery rates are high, market prices for carbon could pay the full price of restoration, with additional independent investment needed in cases where recovery trajectories are slower. Using carbon markets to fund restoration of degraded native vegetation thereby provides a solution for constrained resources and problematic trade-offs between carbon and biodiversity outcomes. Multi-attribute markets offer the potential to greatly increase the extent of restoration for biodiversity conservation, while providing an affordable source of carbon sequestration and enhancing economic benefits to landowners.

Translation initiation downstream from annotated start codons in human mRNAs coevolves with the Kozak context.

Eukaryotic translation initiation involves preinitiation ribosomal complex 5'-to-3' directional probing of mRNA for codons suitable for starting protein synthesis. The recognition of codons as starts depends on the codon identity and on its immediate nucleotide context known as Kozak context. When the context is weak (i.e., nonoptimal), leaky scanning takes place during which a fraction of ribosomes continues the mRNA probing. We explored the relationship between the context of AUG codons annotated as starts of protein-coding sequences and the next AUG codon occurrence. We found that AUG codons downstream from weak starts occur in the same frame more frequently than downstream from strong starts. We suggest that evolutionary selection on in-frame AUGs downstream from weak start codons is driven by the advantage of the reduction of wasteful out-of-frame product synthesis and also by the advantage of producing multiple proteoforms from certain mRNAs. We confirmed translation initiation downstream from weak start codons using ribosome profiling data. We also tested translation of alternative start codons in 10 specific human genes using reporter constructs. In all tested cases, initiation at downstream start codons was more productive than at the annotated ones. In most cases, optimization of Kozak context did not completely abolish downstream initiation, and in the specific example of CMPK1 mRNA, the optimized start remained unproductive. Collectively, our work reveals previously uncharacterized forces shaping the evolution of protein-coding genes and points to the plurality of translation initiation and the existence of sequence features influencing start codon selection, other than Kozak context.

Evaluation of inter-rater and test-retest reliability for near-infrared spectroscopy reactive hyperemia measures.

BACKGROUND: Near-infrared spectroscopy (NIRS) is a non-invasive tool used to measure blood flow in peripheral tissues. More information on inter-rater agreement and test-retest reliability of NIRS-based reperfusion assessments is needed. PURPOSE: To assess inter-rater agreement for NIRS based data analysis, and evaluate the measurement's reliability across days. METHODS: On three separate days (average days between visits 1 and 3: 19.4 ± 6.9 days), participants' (N = 15 males, 22 ± 2 yr.) post-occlusion reactive hyperemia (PORH) was measured in the left gastrocnemius muscle using Continuous-Wave NIRS (CW-NIRS). A blood pressure cuff was placed proximal to the knee and inflated to occlude lower leg blood flow for 5 min. The following CW-NIRS parameters were selected: (1) percent saturation in HbO2 (StO2%) at baseline; (2) the O2Hb range used to normalize the NIRS signal; (3) the time for the O2Hb signal to reach 50 % peak post-occlusion hyperemia (T1/2), and (4) the post peak hyperemic O2Hb recovery slope (O2REC-SLP). Absolute agreement between the two analysts was calculated using two-way random effects Intraclass Correlation Coefficients (ICC2,1). Consistency between analysts and across days was calculated using two-way mixed models (ICC3,1). Mean and 95 % confidence intervals (CI) of ICCs are reported. Coefficient of variation (CV) and standard error of the measurement (SEM) are reported. RESULTS: The ICC2,1 data indicated "adequate" to "excellent" absolute agreement between the two NIRS analysts. ICC2,3 data indicated "adequate" to "good" reliability across visits. The CV and SEM for rater 1 and rater 2 across visit were StO2 (CV: 3.79 % ± 2.71 % and 4.50 % ± 2.37 %; SEM: 3.42 and 3.82), O2Hb range (CV: 10.50 ± 5.93 and 12.79 ± 12.41; SEM: 3.26 and 4.71), T1/2 (CV: 11.15 % ± 5.52 % and 10.96 % ± 4.50; SEM: 1.22 and 1.11), and O2REC-SLP (CV: 19.49 % ± 9.99 % and 18.45 % ± 9.48 %; SEM: 0.04 and 0.04). CONCLUSION: It is concluded that NIRS parameters assessed show adequate reliability between analysts and across three visits. It is recommended, when feasible and because of the absence of 100 % reliability, that investigators employ more than one rater for scoring at least a portion of the data across each trial in a study's control condition in order to have the ability to estimate the magnitude of error attributable to imperfect reliability.

Separate But Not Equal? A Cross-Sectional Study of Segregation by Payor Mix in Academic Primary Care Clinics.

BACKGROUND: At some US Academic Health Centers (AHCs), patients with predominantly Medicaid insurance are seen in one clinic and patients with other insurance are seen in another. The extent of this practice and implications are unknown. OBJECTIVE: To estimate the proportion of AHCs that have at least two primary care internal medicine clinics that differ substantially in proportion of patients with Medicaid and to compare patient demographic, staffing, and operational features. PARTICIPANTS: General internal medicine chiefs and clinic directors at 40 randomly selected US AHCs plus the top 10 AHCs in terms of NIH funding. MAIN MEASURE: An AHC was classified as maintaining clinics that differed substantially in the proportion of patients with Medicaid if any two differed by ≥ 40% (absolute). Other criteria were used for pre-specified secondary analyses (e.g., ≥ 30%). KEY RESULTS: Thirty-nine of 50 AHCs (78%) participated. Four of 39 (10%; 95% CI, 3 to 24%) had two clinics differing by ≥ 40% in the proportion of patients with Medicaid, eight (21%; 95% CI, 9 to 36%) had clinics differing by ≥ 30%, and 15 (38%; 95% CI, 23 to 55%) had clinics differing by ≥ 20%. Clinics with more patients with Medicaid by any of the three criteria were more likely to employ resident physicians as providers of longitudinal care (with faculty supervision) and more likely to have patients who were Black or Hispanic. CONCLUSIONS: Some US AHCs maintain separate clinics defined by the proportion of patients with Medicaid. Clinics with a higher proportion of patients insured by Medicaid are more likely to employ residents (with faculty oversight), feature residents as providers of longitudinal care, and serve patients who are Black and Hispanic. Further research is needed to understand why some AHCs have primary care clinics distinguishable by insurance mix with the goal of ensuring that racism and discrimination are not root causes.

Progress Toward Rubella Elimination - World Health Organization South-East Asia Region, 2013-2021.

During 2013, the 11 countries of the World Health Organization (WHO) South-East Asia Region* (SEAR) adopted the goals of measles elimination and rubella and congenital rubella syndrome (CRS) control† by 2020. During 2019, SEAR countries declared a broader goal for eliminating both measles and rubella§ by 2023 (1). Before 2013, only five SEAR countries had introduced rubella-containing vaccine (RCV). This report updates a previous report and describes progress toward rubella elimination in SEAR during 2013-2021 (2). During 2013-2021, six SEAR countries introduced RCV; all countries in the Region now use RCV in routine immunization. Routine immunization coverage with the first dose of a rubella-containing vaccine (RCV1) increased >600%, from 12% during 2013 to 86% during 2021, and an estimated 515 million persons were vaccinated via RCV supplementary immunization activities (SIAs)¶ during 2013-2021. During this time, annual reported rubella incidence declined by 80%, from 5.5 to 1.1 cases per million population. Maldives and Sri Lanka are verified as having achieved rubella elimination; Bhutan, North Korea, and Timor-Leste have halted endemic transmission of rubella virus for >36 months. SEAR has made substantial progress toward rubella elimination; however, intensified measures are needed to achieve elimination.

Progress Toward Measles Elimination - African Region, 2017-2021.

Worldwide, measles remains a major cause of disease and death; the highest incidence is in the World Health Organization African Region (AFR). In 2011, the 46 AFR member states established a goal of regional measles elimination by 2020; this report describes progress during 2017-2021. Regional coverage with a first dose of measles-containing vaccine (MCV) decreased from 70% in 2017 to 68% in 2021, and the number of countries with ≥95% coverage decreased from six (13%) to two (4%). The number of countries providing a second MCV dose increased from 27 (57%) to 38 (81%), and second-dose coverage increased from 25% to 41%. Approximately 341 million persons were vaccinated in supplementary immunization activities, and an estimated 4.5 million deaths were averted by vaccination. However, the number of countries meeting measles surveillance performance indicators declined from 26 (62%) to nine (22%). Measles incidence increased from 69.2 per 1 million population in 2017 to 81.9 in 2021. The number of estimated annual measles cases and deaths increased 22% and 8%, respectively. By December 2021, no country in AFR had received verification of measles elimination. To achieve a renewed regional goal of measles elimination in at least 80% of countries by 2030, intensified efforts are needed to recover and surpass levels of surveillance performance and coverage with 2 MCV doses achieved before the COVID-19 pandemic.

Progress Toward Measles Elimination - Worldwide, 2000-2022.

Measles is a highly contagious, vaccine-preventable disease that requires high population immunity for transmission to be interrupted. All six World Health Organization regions have committed to eliminating measles; however, no region has achieved and sustained measles elimination. This report describes measles elimination progress during 2000-2022. During 2000-2019, estimated coverage worldwide with the first dose of measles-containing vaccine (MCV) increased from 72% to 86%, then declined to 81% in 2021 during the COVID-19 pandemic, representing the lowest coverage since 2008. In 2022, first-dose MCV coverage increased to 83%. Only one half (72) of 144 countries reporting measles cases achieved the measles surveillance indicator target of two or more discarded cases per 100,000 population in 2022. During 2021-2022, estimated measles cases increased 18%, from 7,802,000 to 9,232,300, and the number of countries experiencing large or disruptive outbreaks increased from 22 to 37. Estimated measles deaths increased 43% during 2021-2022, from 95,000 to 136,200. Nonetheless, an estimated 57 million measles deaths were averted by vaccination during 2000-2022. In 2022, measles vaccination coverage and global surveillance showed some recovery from the COVID-19 pandemic setbacks; however, coverage declined in low-income countries, and globally, years of suboptimal immunization coverage left millions of children unprotected. Urgent reversal of coverage setbacks experienced during the COVID-19 pandemic can be accomplished by renewing efforts to vaccinate all children with 2 MCV doses and strengthening surveillance, thereby preventing outbreaks and accelerating progress toward measles elimination.

Streptomyces rare codon UUA: from features associated with 2 adpA related locations to candidate phage regulatory translational bypassing.

In Streptomyces species, the cell cycle involves a switch from an early and vegetative state to a later phase where secondary products including antibiotics are synthesized, aerial hyphae form and sporulation occurs. AdpA, which has two domains, activates the expression of numerous genes involved in the switch from the vegetative growth phase. The adpA mRNA of many Streptomyces species has a UUA codon in a linker region between 5' sequence encoding one domain and 3' sequence encoding its other and C-terminal domain. UUA codons are exceptionally rare in Streptomyces, and its functional cognate tRNA is not present in a fully modified and acylated form, in the early and vegetative phase of the cell cycle though it is aminoacylated later. Here, we report candidate recoding signals that may influence decoding of the linker region UUA. Additionally, a short ORF 5' of the main ORF has been identified with a GUG at, or near, its 5' end and an in-frame UUA near its 3' end. The latter is commonly 5 nucleotides 5' of the main ORF start. Ribosome profiling data show translation of that 5' region. Ten years ago, UUA-mediated translational bypassing was proposed as a sensor by a Streptomyces phage of its host's cell cycle stage and an effector of its lytic/lysogeny switch. We provide the first experimental evidence supportive of this proposal.

Unusually efficient CUG initiation of an overlapping reading frame in POLG mRNA yields novel protein POLGARF.

While near-cognate codons are frequently used for translation initiation in eukaryotes, their efficiencies are usually low (<10% compared to an AUG in optimal context). Here, we describe a rare case of highly efficient near-cognate initiation. A CUG triplet located in the 5' leader of POLG messenger RNA (mRNA) initiates almost as efficiently (∼60 to 70%) as an AUG in optimal context. This CUG directs translation of a conserved 260-triplet-long overlapping open reading frame (ORF), which we call POLGARF (POLG Alternative Reading Frame). Translation of a short upstream ORF 5' of this CUG governs the ratio between POLG (the catalytic subunit of mitochondrial DNA polymerase) and POLGARF synthesized from a single POLG mRNA. Functional investigation of POLGARF suggests a role in extracellular signaling. While unprocessed POLGARF localizes to the nucleoli together with its interacting partner C1QBP, serum stimulation results in rapid cleavage and secretion of a POLGARF C-terminal fragment. Phylogenetic analysis shows that POLGARF evolved ∼160 million y ago due to a mammalian-wide interspersed repeat (MIR) transposition into the 5' leader sequence of the mammalian POLG gene, which became fixed in placental mammals. This discovery of POLGARF unveils a previously undescribed mechanism of de novo protein-coding gene evolution.

Valuing Protected Area Tourism Ecosystem Services Using Big Data.

Economic value from protected areas informs decisions for biodiversity conservation and visitor benefits. Calculating these benefits assists governments to allocate limited budget resources. This study estimated tourism ecosystem service expenditure values for a regional protected area network in South Australia (57 parks) using direct transactional data, travel costs and economic multipliers. The big dataset came from a comprehensive booking system, which helped overcome common limitations associated with survey data (e.g., key areas rather than full network and high zero-value observations). Protected areas returned AU$373.8 million in the 2018-19 base year to the South Australian economy. The results indicate that combined estimation methods coupled to big data sets provide information on baseline expenditure to engage with critical conservation and tourism sites (e.g., Kangaroo Island). In this case they offer a unique full area network expenditure estimate which is an improvement on typical survey approaches, highlighting the advantage of protected area managers investing in big data. Finally, as South Australian protected areas exceed that in many other contexts the study offers important inputs to funding narratives and protected area expansion in line with global assessment targets.

Postcranial skeletal pneumaticity in non-aquatic neoavians: Insights from accipitrimorphae.

Postcranial skeletal pneumaticity, air-filled bones of the trunk and limbs, is exclusive to birds among extant tetrapods and exhibits significant variation in its expression among different species. Such variation is not random but exhibits relationships with both body mass and locomotor specializations. Most species-level comparative research to date has focused on aquatic-oriented taxa (e.g., Anseriformes). The lack of data from non-aquatic birds constrains our ability to characterize global (i.e., avian-wide) patterns of this trait complex. To address this gap, the study conducted herein quantified postcranial pneumaticity in Accipitrimorphae, a mostly terrestrial clade composed of species that span a range of body sizes and exhibit diverse flight/foraging behaviors. All examined species (n = 88) invariably pneumatized the postaxial through pre-caudal vertebrae, sternum, coracoid, humerus, vertebral and sternal ribs, and pelvic girdle, a pattern herein referred to as the accipitrimorph baseline. Of the 88 sampled species, 41 expanded upon this pattern, whereas 10 species exhibited a reduction. No species deviated from the accipitrimorph baseline by more than two anatomical regions. A phylogenetically-informed regression analysis failed to identify a significant relationship between body mass and pneumaticity. However, specific pneumaticity phenotypes deviating from the baseline were correlated with aspects of wing morphology, tail length, and home range size. Results from this and previous studies provide clarity on two hypotheses: (1) aquatic taxa display distinct pneumaticity expression patterns relative to non-aquatic birds, notably with reductions in the proportion of the skeleton filled with air in diving specialists and (2) contemporary comparative studies, including the one herein, that explicitly account for phylogenetic relationships consistently fail to support the oft-cited positive relationship between pneumaticity and body mass. Instead, historical relationships and functional/ecological attributes (e.g., diving, specialized flight behaviors) appear to be the primary drivers underlying patterns of variation in this trait complex.

Progress Toward Regional Measles Elimination - Worldwide, 2000-2021.

All six World Health Organization (WHO) regions have committed to eliminating measles.* The Immunization Agenda 2021-2030 (IA2030)† aims to achieve the regional targets as a core indicator of impact and positions measles as the tracer of a health system's ability to deliver essential childhood vaccines. IA2030 highlights the importance of ensuring rigorous measles surveillance systems to document immunity gaps and achieve 95% coverage with 2 timely doses of measles-containing vaccine (MCV) among children. This report describes progress toward measles elimination during 2000-2021 and updates a previous report (1). During 2000-2021, estimated global coverage with a first MCV dose (MCV1) increased from 72% to a peak of 86% in 2019, but decreased during the COVID-19 pandemic to 83% in 2020 and to 81% in 2021, the lowest MCV1 coverage recorded since 2008. All countries conducted measles surveillance, but only 47 (35%) of 135 countries reporting discarded cases§ achieved the sensitivity indicator target of two or more discarded cases per 100,000 population in 2021, indicating surveillance system underperformance in certain countries. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, then rebounded to 120 in 2019 during a global resurgence (2), before declining to 21 in 2020 and to 17 in 2021. Large and disruptive outbreaks were reported in 22 countries. During 2000-2021, the annual number of estimated measles deaths decreased 83%, from 761,000 to 128,000; an estimated 56 million measles deaths were averted by vaccination. To regain progress and achieve regional measles elimination targets during and after the COVID-19 pandemic, accelerating targeted efforts is necessary to reach all children with 2 MCV doses while implementing robust surveillance and identifying and closing immunity gaps to prevent cases and outbreaks.

Change in Alcohol Use Based on Self-Report and a Quantitative Biomarker, Phosphatidylethanol, in People With HIV.

The timeline followback (TLFB) takes more resources to collect than the Alcohol Use Disorder Identification Test (AUDIT-C). We assessed agreement of TLFB and AUDIT-C with the biomarker phosphatidylethanol (PEth) and compared changes in TLFB and PEth among persons with HIV (PWH) using secondary data from randomized trials. We calculated operating characteristics and agreement between TLFB (> 1 and > 2 average drinks/day), AUDIT-C ≥ 4 and PEth ≥ 20 among 275 men with HIV. Median age was 57 years, 80% were African-American; and 17% white. Sixty-eight percent had PEth ≥ 20, 46% reported > 2 average drinks/day on TLFB, 61% reported > 1 average drinks/day on TLFB, and 72% had an AUDIT-C ≥ 4. Relative to PEth, sensitivity for AUDIT-C ≥ 4 was 84% (kappa = 0.36), and for TLFB > 1 average drink/day was 76% (kappa = 0.44). Change in alcohol use appeared greater using TLFB measures than PEth. Strategies to robustly assess alcohol use in PWH may require both self-report and biomarkers.

Models for Implementing Emergency Department-Initiated Buprenorphine With Referral for Ongoing Medication Treatment at Emergency Department Discharge in Diverse Academic Centers.

There has been a substantial rise in the number of publications and training opportunities on the care and treatment of emergency department (ED) patients with opioid use disorder over the past several years. The American College of Emergency Physicians recently published recommendations for providing buprenorphine to patients with opioid use disorder, but barriers to implementing this clinical practice remain. We describe the models for implementing ED-initiated buprenorphine at 4 diverse urban, academic medical centers across the country as part of a federally funded effort termed "Project ED Health." These 4 sites successfully implemented unique ED-initiated buprenorphine programs as part of a comparison of implementation facilitation to traditional educational dissemination on the uptake of ED-initiated buprenorphine. Each site describes the elements central to the ED process, including screening, treatment initiation, referral, and follow-up, while harnessing organizational characteristics, including ED culture. Finally, we discuss common facilitators to program success, including information technology and electronic medical record integration, hospital-level support, strong connections with outpatient partners, and quality improvement processes.