Using participatory action research to empower district hospital staff to deliver quality-assured essential surgery to rural populations in Malawi, Zambia, and Tanzania.

Background: In 2017 the SURG-Africa project set out to institute a surgical, obstetric, trauma and anesthesia (SOTA) care capacity-building intervention focused on non-specialist providers at district hospitals in Zambia, Malawi and Tanzania. The aim was to scale up quality-assured SOTA care for rural populations. This paper reports the process of developing the intervention and our experience of initial implementation, using a participatory approach. Methods: Participatory Action Research workshops were held in the 3 countries in July-October 2017 and in October 2018-July 2019, involving representatives of key local stakeholder groups: district hospital (DH) surgical teams and administrators, referral hospital SOTA specialists, professional associations and local authorities. Through semi-structured discussions, qualitative data were collected on participants' perceptions and experiences of barriers to the provision of SOTA care at district level, and on the training and supervision needs of district surgical teams. Data were compared for themes across countries and across surgical team cadres. Results: All groups reported a lack of in-service training to develop essential skills to manage common SOTA cases; use and care of equipment; essential anesthesia care including resuscitation skills; and infection prevention and control. Very few district surgical teams had access to supervision. SOTA providers at DHs reported a demand for more feedback on referrals. Participants prioritized training needs that could be addressed through regular in-service training and supervision visits from referral hospital specialists to DHs. These data were used by participants in an action-planning cycle to develop site-specific training plans for each research site. Conclusion: The inclusive, participatory approach to stakeholder involvement in SOTA system strengthening employed by this study supported the design of a locally relevant and contextualized intervention. This study provides lessons on how to rebalance power dynamics in Global Surgery, through giving a voice to district surgical teams.

First reported detection of the mobile colistin resistance genes, mcr-8 and mcr-9, in the Irish environment.

The emergence and dissemination of mobile colistin resistance (mcr) genes across the globe poses a significant threat to public health, as colistin remains one of the last line treatment options for multi-drug resistant infections. Environmental samples (157 water and 157 wastewater) were collected in Ireland between 2018 and 2020. Samples collected were assessed for the presence of antimicrobial resistant bacteria using Brilliance ESBL, Brilliance CRE, mSuperCARBA and McConkey agar containing a ciprofloxacin disc. All water and integrated constructed wetland influent and effluent samples were filtered and enriched in buffered peptone water prior to culture, while wastewater samples were cultured directly. Isolates collected were identified via MALDI-TOF, were tested for susceptibility to 16 antimicrobials, including colistin, and subsequently underwent whole genome sequencing. Overall, eight mcr positive Enterobacterales (one mcr-8 and seven mcr-9) were recovered from six samples (freshwater (n = 2), healthcare facility wastewater (n = 2), wastewater treatment plant influent (n = 1) and integrated constructed wetland influent (piggery farm waste) (n = 1)). While the mcr-8 positive K. pneumoniae displayed resistance to colistin, all seven mcr-9 harbouring Enterobacterales remained susceptible. All isolates demonstrated multi-drug resistance and through whole genome sequencing analysis, were found to harbour a wide variety of antimicrobial resistance genes i.e., 30 ± 4.1 (10-61), including the carbapenemases, blaOXA-48 (n = 2) and blaNDM-1 (n = 1), which were harboured by three of the isolates. The mcr genes were located on IncHI2, IncFIIK and IncI1-like plasmids. The findings of this study highlight potential sources and reservoirs of mcr genes in the environment and illustrate the need for further research to gain a better understanding of the role the environment plays in the persistence and dissemination of antimicrobial resistance.

Characterization of Shiga toxin-producing Escherichia coli presence, serogroups and risk factors from private groundwater sources in western Ireland.

Over recent years, Ireland has reported the highest crude incidence rates of Shiga toxin-producing Escherichia coli (STEC) enteritis in Europe. Unregulated private groundwater sources have emerged as an important potential transmission route for STEC, with up to 750,000 Irish residents reliant on these sources for domestic waters. This study aimed to investigate the prevalence and serogroup profile of STEC contamination from domestic private wells in western Ireland. Fifty-two groundwater sources were analysed during two sampling campaigns in the autumn (September/October) of 2019 (n = 21) and 2021 (n = 31). Untreated groundwater samples (30 L) were collected and analysed using the "CapE" (capture, amplify, extract) method. Extracted DNA was tested using multiplex real-time PCR for Shiga toxin stx1 and/or stx2 and eae genes. STEC positive DNA samples were tested for clinically relevant serogroups by real-time PCR. Data relating to 27 potential groundwater contamination risk factors were geospatially linked to each well and assessed for association with E. coli, stx1 and/or stx2 and eae presence/absence. Overall, 20/52 wells (38.4 %) were positive for E. coli (median concentration 8.5 MPN/100 mL as assessed by Colilert-18 method). Stx1 and/or stx2 was detected in 10/52 (19.2 %) wells overall and 8/20 E. coli positive wells, equating to a STEC to "generic" E. coli detection ratio of 40 %. Six of these wells (30 %) were also positive for eae. One or more serogroup-specific gene targets were identified in all but one stx1 and/or stx2 positive sample, with O145 (n = 6), O157 (n = 5) and O103 (n = 4) most prevalent. STEC presence was significantly associated with decreasing well depth (U = -2.243; p = 0.024) and increasing 30-day mean antecedent rainfall (U = 2.126; p = 0.034). Serogroup O104 was associated with increased sheep density (U = 2.089; p = 0.044) and detection of stx1 and/or stx2 + eae with increased septic tank density (U = 2.246 p = 0.023). Findings indicate high detection rates of clinically relevant STEC in E. coli contaminated groundwater sources in Ireland.

Global survey shows planners use widely varying sea-level rise projections for coastal adaptation.

Including sea-level rise (SLR) projections in planning and implementing coastal adaptation is crucial. Here we analyze the first global survey on the use of SLR projections for 2050 and 2100. Two-hundred and fifty-three coastal practitioners engaged in adaptation/planning from 49 countries provided complete answers to the survey which was distributed in nine languages - Arabic, Chinese, English, French, Hebrew, Japanese, Korean, Portuguese and Spanish. While recognition of the threat of SLR is almost universal, only 72% of respondents currently utilize SLR projections. Generally, developing countries have lower levels of utilization. There is no global standard in the use of SLR projections: for locations using a standard data structure, 53% are planning using a single projection, while the remainder are using multiple projections, with 13% considering a low-probability high-end scenario. Countries with histories of adaptation and consistent national support show greater assimilation of SLR projections into adaptation decisions. This research provides new insights about current planning practices and can inform important ongoing efforts on the application of the science that is essential to the promotion of effective adaptation.

High Prevalence of Klebsiella pneumoniae in European Food Products: a Multicentric Study Comparing Culture and Molecular Detection Methods.

The Klebsiella pneumoniae species complex (KpSC) is a leading cause of multidrug-resistant human infections. To better understand the potential contribution of food as a vehicle of KpSC, we conducted a multicentric study to define an optimal culture method for its recovery from food matrices and to characterize food isolates phenotypically and genotypically. Chicken meat (n = 160) and salad (n = 145) samples were collected in five European countries and screened for the presence of KpSC using culture-based and zur-khe intergenic region (ZKIR) quantitative PCR (qPCR) methods. Enrichment using buffered peptone water followed by streaking on Simmons citrate agar with inositol (44°C for 48 h) was defined as the most suitable selective culture method for KpSC recovery. A high prevalence of KpSC was found in chicken meat (60% and 52% by ZKIR qPCR and the culture approach, respectively) and salad (30% and 21%, respectively) samples. Genomic analyses revealed high genetic diversity with the dominance of phylogroups Kp1 (91%) and Kp3 (6%). A total of 82% of isolates presented a natural antimicrobial susceptibility phenotype and genotype, with only four CTX-M-15-producing isolates detected. Notably, identical genotypes were found across samples-same food type and same country (15 cases), different food types and same country (1), and same food type and two countries (1)-suggesting high rates of transmission of KpSC within the food sector. Our study provides a novel isolation strategy for KpSC from food matrices and reinforces the view of food as a potential source of KpSC colonization in humans. IMPORTANCE Bacteria of the Klebsiella pneumoniae species complex (KpSC) are ubiquitous, and K. pneumoniae is a leading cause of antibiotic-resistant infections in humans. Despite the urgent public health threat represented by K. pneumoniae, there is a lack of knowledge of the contribution of food sources to colonization and subsequent infection in humans. This is partly due to the absence of standardized methods for characterizing the presence of KpSC in food matrices. Our multicentric study provides and implements a novel isolation strategy for KpSC from food matrices and shows that KpSC members are highly prevalent in salads and chicken meat, reinforcing the view of food as a potential source of KpSC colonization in humans. Despite the large genetic diversity and the low levels of resistance detected, the occurrence of identical genotypes across samples suggests high rates of transmission of KpSC within the food sector, which need to be further explored to define possible control strategies.

A palaeoclimate proxy database for water security planning in Queensland Australia.

Palaeoclimate data relating to hydroclimate variability over the past millennia have a vital contribution to make to the water sector globally. The water industry faces considerable challenges accessing climate data sets that extend beyond that of historical gauging stations. Without this, variability around the extremes of floods and droughts is unknown and stress-testing infrastructure design and water demands is challenging. User-friendly access to relevant palaeoclimate data is now essential, and importantly, an efficient process to determine which proxies are most relevant to a planning scenario, and geographic area of interest. This paper presents PalaeoWISE (Palaeoclimate Data for Water Industry and Security Planning) a fully integrated, and quality-assured database of proxy data extracted from data repositories and publications collated in Linked Paleo Data (LiPD) format. We demonstrate the application of the database in Queensland, one of Australia's most hydrologically extreme states. The database and resultant hydroclimate correlations provides both the scientific community, and water resource managers, with a valuable resource to better manage for future climate changes.

Using family planning service statistics to inform model-based estimates of modern contraceptive prevalence.

The annual assessment of Family Planning (FP) indicators, such as the modern contraceptive prevalence rate (mCPR), is a key component of monitoring and evaluating goals of global FP programs and initiatives. To that end, the Family Planning Estimation Model (FPEM) was developed with the aim of producing survey-informed estimates and projections of mCPR and other key FP indictors over time. With large-scale surveys being carried out on average every 3-5 years, data gaps since the most recent survey often exceed one year. As a result, survey-based estimates for the current year from FPEM are often based on projections that carry a larger uncertainty than data informed estimates. In order to bridge recent data gaps we consider the use of a measure, termed Estimated Modern Use (EMU), which has been derived from routinely collected family planning service statistics. However, EMU data come with known limitations, namely measurement errors which result in biases and additional variation with respect to survey-based estimates of mCPR. Here we present a data model for the incorporation of EMU data into FPEM, which accounts for these limitations. Based on known biases, we assume that only changes in EMU can inform FPEM estimates, while also taking inherent variation into account. The addition of this EMU data model to FPEM allows us to provide a secondary data source for informing and reducing uncertainty in current estimates of mCPR. We present model validations using a survey-only model as a baseline comparison and we illustrate the impact of including the EMU data model in FPEM. Results show that the inclusion of EMU data can change point-estimates of mCPR by up to 6.7 percentage points compared to using surveys only. Observed reductions in uncertainty were modest, with the width of uncertainty intervals being reduced by up to 2.7 percentage points.

Fpemlocal: Estimating family planning indicators in R for a single population of interest.

The global Family Planning Estimation model (FPEM) combines a Bayesian hierarchical model with country-specific time trends to yield estimates of contraceptive prevalence and unmet need for family planning for countries worldwide. In this paper, we introduce the R package fpemlocal that carries out the estimation of family planning indicators for a single population, for example, for a single country or smaller area. In this implementation of FPEM, all non-population-specific parameters are fixed at outcomes obtained in a prior global FPEM run. The development of this model was motivated by the demand for computational efficiency, without loss of model accuracy, when estimates and projections from FPEM were needed only for a single country. We present use cases to produce estimates for a single population of women by union status or all women based on package-provided data bases and user-specified data. We also explain how to aggregate estimates across multiple populations. The R package forms the basis of the Track20 Family Planning Estimation Tool to monitor trends in family planning indicators for the FP2020 initiative. Fpemlocal is available from: https://github.com/AlkemaLab/fpemlocal.

Common Era sea-level budgets along the U.S. Atlantic coast.

Sea-level budgets account for the contributions of processes driving sea-level change, but are predominantly focused on global-mean sea level and limited to the 20th and 21st centuries. Here we estimate site-specific sea-level budgets along the U.S. Atlantic coast during the Common Era (0-2000 CE) by separating relative sea-level (RSL) records into process-related signals on different spatial scales. Regional-scale, temporally linear processes driven by glacial isostatic adjustment dominate RSL change and exhibit a spatial gradient, with fastest rates of rise in southern New Jersey (1.6 ± 0.02 mm yr-1). Regional and local, temporally non-linear processes, such as ocean/atmosphere dynamics and groundwater withdrawal, contributed between -0.3 and 0.4 mm yr-1 over centennial timescales. The most significant change in the budgets is the increasing influence of the common global signal due to ice melt and thermal expansion since 1800 CE, which became a dominant contributor to RSL with a 20th century rate of 1.3 ± 0.1 mm yr-1.

A Point Prevalence Survey of Antibiotic Resistance in the Irish Environment, 2018-2019.

Water bodies worldwide have proven to be vast reservoirs of clinically significant antibiotic resistant organisms. Contamination of waters by anthropogenic discharges is a significant contributor to the widespread dissemination of antibiotic resistance. The aim of this research was to investigate multiple different anthropogenic sources on a national scale for the role they play in the environmental propagation of antibiotic resistance. A total of 39 water and 25 sewage samples were collected across four local authority areas in the West, East and South of Ireland. In total, 211 Enterobacterales were isolated (139 water, 72 sewage) and characterised. A subset of isolates (n=60) were chosen for whole genome sequencing. Direct comparisons of the water versus sewage isolate collections revealed a higher percentage of sewage isolates displayed resistance to cefoxitin (46%) and ertapenem (32%), while a higher percentage of water isolates displayed resistance to tetracycline (55%) and ciprofloxacin (71%). Half of all isolates displayed extended spectrum beta-lactamase (ESBL) production phenotypically (n = 105/211; 50%), with blaCTX-M detected in 99/105 isolates by PCR. Carbapenemase genes were identified in 11 isolates (6 sewage, 5 water). The most common variant was blaOXA-48 (n=6), followed by blaNDM-5 (n=2) and blaKPC-2 (n=2). Whole genome sequencing analysis revealed numerous different sequence types in circulation in both waters and sewage including E. coli ST131 (n=15), ST38 (n=8), ST10 (n=4) along with Klebsiella ST405 (n=3) and ST11 (n=2). Core genome MLST (cgMLST) comparisons uncovered three highly similar Klebsiella isolates originating from hospital sewage and two nearby waters. The Klebsiella isolates from an estuary and seawater displayed 99.1% and 98.8% cgMLST identity to the hospital sewage isolate respectively. In addition, three pairs of E. coli isolates from different waters also revealed cgMLST similarities, indicating widespread dissemination and persistence of certain strains in the aquatic environment. These findings highlight the need for routine monitoring of water bodies used for recreational and drinking purposes for the presence of multi-drug resistant organisms.

What increase in modern contraceptive use is needed in FP2020 countries to reach 75% demand satisfied by 2030? An assessment using the Accelerated Transition Method and Family Planning Estimation Model.

Background: Sustainable Development Goal 3.7 aims to ensure universal access to sexual and reproductive health services. One suggested benchmark is to have at least 75% of the demand for contraception satisfied with modern methods (DS) in all countries by 2030. The translation of DS-based targets into targets for the modern contraceptive prevalence rate (mCPR) is needed to make targets actionable. Methods: We propose the Accelerated Transition (AT) method for determining the mCPR needed to reach demand-satisfied targets by 2030. The starting point for this method is the projection of DS under "business as usual" using the one-country implementation of the Family Planning Estimation Model (FPEMcountry). For countries in which the DS target is projected to be later than 2030, the AT method assumes that meeting the DS target by 2030 requires an acceleration of the contraceptive use transition such that the DS target, and its associated mCPR, will be reached in 2030 as opposed to the later year. The DS-target-associated mCPR becomes the mCPR target for the year 2030. Results: We apply the AT method to assess progress needed for attaining the 75% DS target for married or in-union women in the world's poorest countries. For 50 out of 68 countries, we estimate that accelerations are needed, with required mCPR increases ranging from 4.3 to 50.8 percentage points. Conclusions: The AT method quantifies the acceleration needed - as compared to business as usual projections - for a country to meet a family planning target. The method can be used to determine the mCPR needed to reach demand-satisfied targets.

A 2,000-year Bayesian NAO reconstruction from the Iberian Peninsula.

The North Atlantic Oscillation (NAO) is the major atmospheric mode that controls winter European climate variability because its strength and phase determine regional temperature, precipitation and storm tracks. The NAO spatial structure and associated climatic impacts over Europe are not stationary making it crucial to understanding its past evolution in order to improve the predictability of future scenarios. In this regard, there has been a dramatic increase in the number of studies aimed at reconstructing past NAO variability, but the information related to decadal-scale NAO evolution beyond the last millennium is scarce and inconclusive. We present a new 2,000-year multi-annual, proxy-based reconstruction of local NAO impact, with associated uncertainties, obtained by a Bayesian approach. This new local NAO reconstruction is obtained from a mountain lacustrine sedimentary archive of the Iberian Peninsula. This geographical area is not included in previous NAO reconstructions despite being a widely used region for instrumental-based NAO measurements. We assess the main external forcings (i.e., volcanic eruptions and solar activity) on NAO variability which, on a decadal scale, show that a low number of sunspots correlate to low NAO values. By comparison with other previously published NAO reconstructions in our analyses we can test the stationarity of the solar influence on the NAO signal across a latitudinal gradient based on the position of the employed archives for each NAO reconstruction. Inconclusive results on the volcanic forcing on NAO variability over decadal time-scales indicates the need for further studies. Moreover, we highlight the potential role of other North Atlantic modes of variability (i.e., East Atlantic pattern) on the non-stationary behaviour of the NAO throughout the Common Era, likely via solar forcing.

Recreational waters - A potential transmission route for SARS-CoV-2 to humans?

Coronavirus disease 2019 (COVID-19), the respiratory illness caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has lead to high morbidity and mortality rates worldwide, has been causing major public health concerns since first detected in late 2019. Following identification of novel pathogens, questions in relation to dissemination of the pathogen and transmission routes begin to emerge. This rapidly spreading SARS-CoV-2 virus has been detected in both faecal and wastewater samples across the globe, highlighting the potential for faecal-oral transmission of the virus. As a result, concerns regarding the transmission of the virus in the environment and the risk associated with contracting the virus in recreational waters, particularly where inadequately treated wastewater is discharged, have been emerging in recent weeks. This paper highlights the need for further research to be carried out to investigate the presence, infectivity and viability of this newly identified SARS-CoV-2 virus in wastewater effluent and receiving recreational waters.

Detection of OXA-48-like-producing Enterobacterales in Irish recreational water.

The rapid dissemination of carbapenemase-producing Enterobacterales (CPE) is a major public health concern. The role that the aquatic environment plays in this dissemination is underexplored. This study aimed to examine seawater as a reservoir for CPE. Seawater sampling took place at a bathing site throughout the 2017 bathing season. Each 30 L sample (n = 6) was filtered using the CapE filtration system. Wastewater samples (200 mL) (pre-treatment (n = 3) and post-treatment (n = 3)) were obtained from a nearby secondary wastewater treatment plant, during the same time period. All samples were examined for CPE. Whole genome sequencing of confirmed CPE was carried out using Illumina sequencing. Isolate genomes were hosted in corresponding BIGSdb databases and analyses were performed using multiple web-based tools. CPE was detected in 2/6 seawater samples. It was not detected in any wastewater samples. OXA-48-like-producing ST131 Escherichia coli (Ec_BM707) was isolated from a seawater sample collected in May 2017 and OXA-48-like-producing ST101 Klebsiella pneumoniae (Kp_BM758) was isolated from a seawater sample collected in August 2017. The genomes of the environmental isolates were compared to a collection of previously described Irish clinical OXA-48-like-producing Enterobacterales (n = 105). Ec_BM707 and Kp_BM758 harboured blaOXA-48 on similar mobile genetic elements to those identified in the clinical collection (pOXA-48 fragment in Ec_BM707 and IncL(pOXA-48) plasmid in Kp_BM758). Genetic similarities were observed between Ec_BM707 and several of the clinical ST131 E. coli, with allele matches at up to 98.2% of 2513 core genome multilocus sequence type (cgMLST) loci. In contrast, Kp_BM758 and the 34 clinical K. pneumoniae were genetically distant. The source of the CPE at this site was not identified. The detection of OXA-48-like-producing ST131 E. coli and OXA-48-like-producing ST101 K. pneumoniae in Irish recreational water is a concern. The potential for contamination of the aquatic environment to contribute to dissemination of CPE in Europe warrants further study.

Hospital effluent: A reservoir for carbapenemase-producing Enterobacterales?

Antimicrobial resistance is a major public health concern. Carbapenemase-producing Enterobacterales (CPE) represent a significant health threat as some strains are resistant to almost all available antibiotics. The aim of this research was to examine hospital effluent and municipal wastewater in an urban area in Ireland for CPE. Samples of hospital effluent (n = 5), municipal wastewater before (n = 5) and after (n = 4) the hospital effluent stream joined the municipal wastewater stream were collected over a nine-week period (May-June 2017). All samples were examined for CPE by direct plating onto Brilliance CRE agar. Isolates were selected for susceptibility testing to 15 antimicrobial agents in accordance with EUCAST criteria. Where relevant, isolates were tested for carbapenemase-encoding genes by real-time PCR. CPE were detected in five samples of hospital effluent, one sample of pre-hospital wastewater and three samples of post-hospital wastewater. Our findings suggest hospital effluent is a major contributor to CPE in municipal wastewater. Monitoring of hospital effluent for CPE could have important applications in detection and risk management of unrecognised dissemination of CPE in both the healthcare setting and the environment.

Predicting marsh vulnerability to sea-level rise using Holocene relative sea-level data.

Tidal marshes rank among Earth's vulnerable ecosystems, which will retreat if future rates of relative sea-level rise (RSLR) exceed marshes' ability to accrete vertically. Here, we assess the limits to marsh vulnerability by analyzing >780 Holocene reconstructions of tidal marsh evolution in Great Britain. These reconstructions include both transgressive (tidal marsh retreat) and regressive (tidal marsh expansion) contacts. The probability of a marsh retreat was conditional upon Holocene rates of RSLR, which varied between -7.7 and 15.2 mm/yr. Holocene records indicate that marshes are nine times more likely to retreat than expand when RSLR rates are ≥7.1 mm/yr. Coupling estimated probabilities of marsh retreat with projections of future RSLR suggests a major risk of tidal marsh loss in the twenty-first century. All of Great Britain has a >80% probability of a marsh retreat under Representative Concentration Pathway (RCP) 8.5 by 2100, with areas of southern and eastern England achieving this probability by 2040.

Modern contraceptive use, unmet need, and demand satisfied among women of reproductive age who are married or in a union in the focus countries of the Family Planning 2020 initiative: a systematic analysis using the Family Planning Estimation Tool.

BACKGROUND: The London Summit on Family Planning in 2012 inspired the Family Planning 2020 (FP2020) initiative and the 120×20 goal of having an additional 120 million women and adolescent girls become users of modern contraceptives in 69 of the world's poorest countries by the year 2020. Working towards achieving 120 × 20 is crucial for ultimately achieving the Sustainable Development Goals of universal access and satisfying demand for reproductive health. Thus, a performance assessment is required to determine countries' progress. METHODS: An updated version of the Family Planning Estimation Tool (FPET) was used to construct estimates and projections of the modern contraceptive prevalence rate (mCPR), unmet need for, and demand satisfied with modern methods of contraception among women of reproductive age who are married or in a union in the focus countries of the FP2020 initiative. We assessed current levels of family planning indicators and changes between 2012 and 2017. A counterfactual analysis was used to assess if recent levels of mCPR exceeded pre-FP2020 expectations. FINDINGS: In 2017, the mCPR among women of reproductive age who are married or in a union in the FP2020 focus countries was 45·7% (95% uncertainty interval [UI] 42·4-49·1), unmet need for modern methods was 21·6% (19·7-23·9), and the demand satisfied with modern methods was 67·9% (64·4-71·1). Between 2012 and 2017 the number of women of reproductive age who are married or in a union who use modern methods increased by 28·8 million (95% UI 5·8-52·5). At the regional level, Asia has seen the mCPR among women of reproductive age who are married or in a union grow from 51·0% (95% UI 48·5-53·4) to 51·8% (47·3-56·5) between 2012 and 2017, which is slow growth, particularly when compared with a change from 23·9% (22·9-25·0) to 28·5% (26·8-30·2) across Africa. At the country level, based on a counterfactual analysis, we found that 61% of the countries that have made a commitment to FP2020 exceeded pre-FP2020 expectations for modern contraceptive use. Country success stories include rapid increases in Kenya, Mozambique, Malawi, Lesotho, Sierra Leone, Liberia, and Chad relative to what was expected in 2012. INTERPRETATION: Whereas the estimate of additional users up to 2017 for women of reproductive age who are married or in a union would suggest that the 120 × 20 goal for all women is overly ambitious, the aggregate outcomes mask the diversity in progress at the country level. We identified countries with accelerated progress, that provide inspiration and guidance on how to increase the use of family planning and inform future efforts, especially in countries where progress has been poor. FUNDING: The Bill & Melinda Gates Foundation, through grant support to the University of Massachusetts Amherst and Avenir Health.

Levels and trends in contraceptive prevalence, unmet need, and demand for family planning for 29 states and union territories in India: a modelling study using the Family Planning Estimation Tool.

BACKGROUND: Improving access to reproductive health services and commodities is central to development. Efforts to assess progress on this front have been largely focused on national estimates, but such analyses can mask local disparities. We assessed progress in reproductive health services subnationally in India. METHODS: We developed a statistical model to generate estimates and projections of levels and trends in family planning indicators for subpopulations. The model builds onto the UN Population Division's Family Planning Estimation Model and uses data from multiple rounds of the Demographic and Health Survey, the District Level Household & Facility Survey, and the Annual Health Survey. We present annual estimates and projections of levels and trends in the prevalence of modern contraceptive use, and unmet need and demand for family planning for 29 states and union territories in India from 1990 to 2030. We also compared projections of demand satisfied with modern methods with the proposed goal of 75%. FINDINGS: There is a large amount of heterogeneity in India, with a difference of up to 55·1 percentage points (95% uncertainty interval 46·4-62·1) in modern contraceptive use in 2015 between subregions. States such as Andhra Pradesh, with 92·7% (90·9-94·2) demand satisfied with modern methods, are performing well above the national average (71·8%, 56·7-83·6), whereas Manipur, with 26·8% (16·7-38·5) of demand satisfied, and Meghalaya, with 45·0% (40·1-50·0), consistently lag behind the rest of the country. Manipur and Meghalaya require the highest percentage increase in modern contraceptive use to achieve 75% demand satisfied with modern methods by 2030. In terms of absolute numbers, Uttar Pradesh requires the greatest increase, needing 9·2 million (5·5-12·6 million) additional users of modern contraception by 2030 to meet the target of 75%. INTERPRETATION: The demand for family planning among the states and union territories in India is highly diverse. Greatest attention is needed in Uttar Pradesh, Manipur, and Meghalaya to meet UN targets. The analysis can be generalised to other countries as well as other subpopulations. FUNDING: Avenir Health through a grant from the Bill & Melinda Gates Foundation.

Site-specific cross-linking analyses reveal an asymmetric protein distribution for a box C/D snoRNP.

Methylation of the ribose 2'-hydroxyl, the most widespread modification of ribosomal and splicesomal RNAs, is guided by the box C/D class of small nucleolar RNAs (snoRNAs). Box C/D small nucleolar ribonucleoproteins (snoRNPs) contain four core proteins: fibrillarin, Nop56, Nop58 and 15.5 kDa. We constructed U25 snoRNAs containing a single photoactivatable 4-thiouridine at each U position within the conserved box C/D and C'/D' motifs. Proteins assembled on the snoRNA after injection into Xenopus oocyte nuclei were identified by cross-linking, and reconstituted particles characterized by functional rescue and mutational analyses. Our data argue that box C/D snoRNPs are asymmetric, with the C' box contacting Nop56 and fibrillarin, the C box interacting with Nop58, and the D and D' boxes contacting fibrillarin. No cross-link to 15.5 kDa was detected; its binding is disrupted by 4-thiouridine substitution in position 1 of the C box. Repositioning the guide sequence of U25 upstream of box D instead of D' revealed that both C/D motifs have the potential to function as guide centers, but, surprisingly, there was no alteration in protein cross-linking.