University of Calabar

There is extensive evidence showing that improving eye health contributes directly and indirectly to achieving many Sustainable Development Goals, including reducing poverty and improving work productivity, general and mental health, and education and equity. Improving eye health is a practical and cost-effective way of unlocking human potential. Eye health needs to be reframed as an enabling, cross-cutting issue within the sustainable development framework.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

We present new techniques for supervised wrapper generation and automated web information extraction, and a system called Lixto implementing these techniques. Our system can generate wrappers which translate relevant pieces of HTML pages into XML. Lixto, of which a working prototype has been implemented, assists the user to semi-automatically create wrapper programs by providing a fully visual and interactive user interface. In this convenient user-interface very expressive extraction programs can be created. Internally, this functionality is reflected by the new logicbased declarative language Elog. Users never have to deal with Elog and even familiarity with HTML is not required. Lixto can be used to create an "XML-Companion" for an HTML web page with changing content, containing the continually updated XML translation of the relevant information. 1

Fifty-nine patients with wounds and ulcers most of which (80 per cent) had failed to heal with conventional treatment were treated with unprocessed honey. Fifty-eight cases showed remarkable improvement following topical application of honey. One case, later diagnosed as Buruli ulcer, failed to respond. Wounds that were sterile at the outset, remained sterile until healed, while infected wounds and ulcer became sterile within 1 week of topical application of honey. Honey debrided wounds rapidly, replacing sloughs with granulation tissue. It also promoted rapid epithelialization, and absorption of oedema from around the ulcer margins.

COVID-19 has further exposed the strong association between race, ethnicity, culture, socioeconomic status and health outcomes and illuminated monumental ethnoracialised differences reflecting the 'colour of disease'. Racism, segregation and inequality have been invisibly and pervasively embedded in dominant cultures and social institutions for decades. The socioeconomic factors that negatively influence health outcomes within the underserved minority communities must be identified and contextualised within historical, political, social and economic remits. Acquisition of disaggregated data will be vital in identifying gaps in the social determinants of these health disparities and tailoring global policy responses.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Summary An analysis of incidence of Phytophthora spp. in 732 European nurseries producing forest transplants, larger specimen trees, landscape plants and ornamentals, plus 2525 areas in which trees and shrubs were planted, is presented based on work conducted by 38 research groups in 23 European countries between 1972 and 2013. Forty‐nine Phytophthora taxa were recorded in 670 nurseries (91.5%); within these nurseries, 1614 of 1992 nursery stands (81.0%) were infested, although most affected plants appeared healthy. In forest and landscape plantings, 56 Phytophthora taxa were recovered from 1667 of 2525 tested sites (66.0%). Affected plants frequently showed symptoms such as crown thinning, chlorosis and dieback caused by extensive fine root losses and/or collar rot. Many well‐known highly damaging host– Phytophthora combinations were frequently detected but 297 and 407 new Phytophthora –host associations were also observed in nurseries and plantings, respectively. On average, 1.3 Phytophthora species/taxa per infested nursery stand and planting site were isolated. At least 47 of the 68 Phytophthora species/taxa detected in nurseries and plantings were exotic species several of which are considered well established in both nurseries and plantings in Europe. Seven known Phytophthora species/taxa were found for the first time in Europe, while 10 taxa had not been previously recorded from nurseries or plantings; in addition, 5 taxa were first detections on woody plant species. Seven Phytophthora taxa were previously unknown to science. The reasons for these failures of plant biosecurity in Europe, implications for forest and semi‐natural ecosystems and possible ways to improve biosecurity are discussed.

Artificial intelligence (AI) is transforming various industries, and education is no exception. Rapid advancements in AI technology have become essential for educators and educational assessment professionals to enhance teaching and learning experiences. AI-powered educational assessment tools provide numerous benefits, including improving the accuracy and efficiency of assessments, generating personalized feedback for students, and enabling teachers to adapt their teaching strategies to meet the unique needs of each student. Therefore, AI has the potential to revolutionize the way education is delivered and assessed, ultimately leading to better educational outcomes for students. This paper explores the various applications of AI tools in educational measurement and assessment. Specifically, it discusses the integration of large language AI models in classroom assessment, in specific areas such as test purpose determination and specification, developing, test blueprint, test item generation/development, preparation of test instructions, item assembly/selection, test administration, test scoring, interpretation of test results, test analysis/appraisal, and reporting. It analyses the role of teachers in AI-based assessment and the challenges of using AI-powered tools in educational assessment. Finally, the paper presents strategies to address these challenges and enhance the effectiveness of AI in educational assessment. In conclusion, using AI in educational assessment has benefits and limitations. As such, educators, policymakers, and stakeholders must work together to develop strategies that maximize the benefits of AI in educational assessment while mitigating the associated risks. The application of AI in educational assessment can ultimately transform education, improve learning outcomes, and equip students with the skills needed to succeed in the 21st century.

BACKGROUND: Unintended pregnancy among adolescents represents an important public health challenge in high-income countries, as well as middle- and low-income countries. Numerous prevention strategies such as health education, skills-building and improving accessibility to contraceptives have been employed by countries across the world, in an effort to address this problem. However, there is uncertainty regarding the effects of these interventions, hence the need to review the evidence-base. OBJECTIVES: To assess the effects of primary prevention interventions (school-based, community/home-based, clinic-based, and faith-based) on unintended pregnancies among adolescents. SEARCH METHODS: We searched all relevant studies regardless of language or publication status up to November 2015. We searched the Cochrane Fertility Regulation Group Specialised trial register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015 Issue 11), MEDLINE, EMBASE, LILACS, Social Science Citation Index and Science Citation Index, Dissertations Abstracts Online, The Gray Literature Network, HealthStar, PsycINFO, CINAHL and POPLINE and the reference lists of articles. SELECTION CRITERIA: We included both individual and cluster randomised controlled trials (RCTs) evaluating any interventions that aimed to increase knowledge and attitudes relating to risk of unintended pregnancies, promote delay in the initiation of sexual intercourse and encourage consistent use of birth control methods to reduce unintended pregnancies in adolescents aged 10 years to 19 years. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and risk of bias, and extracted data. Where appropriate, binary outcomes were pooled using a random-effects model with a 95% confidence interval (Cl). Where appropriate, we combined data in meta-analyses and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 53 RCTs that enrolled 105,368 adolescents. Participants were ethnically diverse. Eighteen studies randomised individuals, 32 randomised clusters (schools (20), classrooms (6), and communities/neighbourhoods (6). Three studies were mixed (individually and cluster randomised). The length of follow up varied from three months to seven years with more than 12 months being the most common duration. Four trials were conducted in low- and middle- income countries, and all others were conducted in high-income countries. Multiple interventionsResults showed that multiple interventions (combination of educational and contraceptive-promoting interventions) lowered the risk of unintended pregnancy among adolescents significantly (RR 0.66, 95% CI 0.50 to 0.87; 4 individual RCTs, 1905 participants, moderate quality evidence. However, this reduction was not statistically significant from cluster RCTs. Evidence on the possible effects of interventions on secondary outcomes (initiation of sexual intercourse, use of birth control methods, abortion, childbirth, sexually transmitted diseases) was not conclusive.Methodological strengths included a relatively large sample size and statistical control for baseline differences, while limitations included lack of biological outcomes, possible self-report bias, analysis neglecting clustered randomisation and the use of different statistical tests in reporting outcomes. Educational interventionsEducational interventions were unlikely to significantly delay the initiation of sexual intercourse among adolescents compared to controls (RR 0.95, 95% CI 0.71 to 1.27; 2 studies, 672 participants, low quality evidence).Educational interventions significantly increased reported condom use at last sex in adolescents compared to controls who did not receive the intervention (RR 1.18, 95% CI 1.06 to 1.32; 2 studies, 1431 participants, moderate quality evidence).However, it is not clear if the educational interventions had any effect on unintended pregnancy as this was not reported by any of the included studies. Contraceptive-promoting interventionsFor adolescents who received contraceptive-promoting interventions, there was little or no difference in the risk of unintended first pregnancy compared to controls (RR 1.01, 95% CI 0.81 to 1.26; 2 studies, 3,440 participants, moderate quality evidence).The use of hormonal contraceptives was significantly higher in adolescents in the intervention group compared to those in the control group (RR 2.22, 95% CI 1.07 to 4.62; 2 studies, 3,091 participants, high quality evidence) AUTHORS' CONCLUSIONS: A combination of educational and contraceptive-promoting interventions appears to reduce unintended pregnancy among adolescents. Evidence for programme effects on biological measures is limited. The variability in study populations, interventions and outcomes of included trials, and the paucity of studies directly comparing different interventions preclude a definitive conclusion regarding which type of intervention is most effective.

BACKGROUND: Diarrhoea accounts for 1.8 million deaths in children in low- and middle-income countries (LMICs). One of the identified strategies to prevent diarrhoea is hand washing. OBJECTIVES: To assess the effects of hand washing promotion interventions on diarrhoeal episodes in children and adults. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register (27 May 2015); CENTRAL (published in the Cochrane Library 2015, Issue 5); MEDLINE (1966 to 27 May 2015); EMBASE (1974 to 27 May 2015); LILACS (1982 to 27 May 2015); PsycINFO (1967 to 27 May 2015); Science Citation Index and Social Science Citation Index (1981 to 27 May 2015); ERIC (1966 to 27 May 2015); SPECTR (2000 to 27 May 2015); Bibliomap (1990 to 27 May 2015); RoRe, The Grey Literature (2002 to 27 May 2015); World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), metaRegister of Controlled Trials (mRCT), and reference lists of articles up to 27 May 2015. We also contacted researchers and organizations in the field. SELECTION CRITERIA: Individually randomized controlled trials (RCTs) and cluster-RCTs that compared the effects of hand washing interventions on diarrhoea episodes in children and adults with no intervention. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. We stratified the analyses for child day-care centres or schools, community, and hospital-based settings. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CIs). We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: We included 22 RCTs: 12 trials from child day-care centres or schools in mainly high-income countries (54,006 participants), nine community-based trials in LMICs (15,303 participants), and one hospital-based trial among people with acquired immune deficiency syndrome (AIDS) (148 participants).Hand washing promotion (education activities, sometimes with provision of soap) at child day-care facilities or schools prevents around one-third of diarrhoea episodes in high income countries (rate ratio 0.70; 95% CI 0.58 to 0.85; nine trials, 4664 participants, high quality evidence), and may prevent a similar proportion in LMICs but only two trials from urban Egypt and Kenya have evaluated this (rate ratio 0.66, 95% CI 0.43 to 0.99; two trials, 45,380 participants, low quality evidence). Only three trials reported measures of behaviour change and the methods of data collection were susceptible to bias. In one trial from the USA hand washing behaviour was reported to improve; and in the trial from Kenya that provided free soap, hand washing did not increase, but soap use did (data not pooled; three trials, 1845 participants, low quality evidence).Hand washing promotion among communities in LMICs probably prevents around one-quarter of diarrhoea episodes (rate ratio 0.72, 95% CI 0.62 to 0.83; eight trials, 14,726 participants, moderate quality evidence). However, six of these eight trials were from Asian settings, with only single trials from South America and sub-Saharan Africa. In six trials, soap was provided free alongside hand washing education, and the overall average effect size was larger than in the two trials which did not provide soap (soap provided: rate ratio 0.66, 95% CI 0.56 to 0.78; six trials, 11,422 participants; education only: rate ratio: 0.84, 95% CI 0.67 to 1.05; two trials, 3304 participants). There was increased hand washing at major prompts (before eating/cooking, after visiting the toilet or cleaning the baby's bottom), and increased compliance to hand hygiene procedure (behavioural outcome) in the intervention groups than the control in community trials (data not pooled: three trials, 3490 participants, high quality evidence).Hand washing promotion for the one trial conducted in a hospital among high-risk population showed significant reduction in mean episodes of diarrhoea (1.68 fewer) in the intervention group (Mean difference 1.68, 95% CI 1.93 to 1.43; one trial, 148 participants, moderate quality evidence). There was increase in hand washing frequency, seven times per day in the intervention group versus three times in the control in this hospital trial (one trial, 148 participants, moderate quality evidence).We found no trials evaluating or reporting the effects of hand washing promotions on diarrhoea-related deaths, all-cause-under five mortality, or costs. AUTHORS' CONCLUSIONS: Hand washing promotion probably reduces diarrhoea episodes in both child day-care centres in high-income countries and among communities living in LMICs by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term.

BACKGROUND: Diarrhoea is a common cause of morbidity and a leading cause of death among children aged less than five years, particularly in low- and middle-income countries. It is transmitted by ingesting contaminated food or drink, by direct person-to-person contact, or from contaminated hands. Hand washing is one of a range of hygiene promotion interventions that can interrupt the transmission of diarrhoea-causing pathogens. OBJECTIVES: To evaluate the effects of interventions to promote hand washing on diarrhoeal episodes in children and adults. SEARCH STRATEGY: In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, PsycINFO, Science Citation Index and Social Science Citation Index, ERIC (1966 to May 2007), SPECTR, Bibliomap, RoRe, The Grey Literature, and reference lists of articles. We also contacted researchers and organizations in the field. SELECTION CRITERIA: Randomized controlled trials, where the unit of randomization is an institution (eg day-care centre), household, or community, that compared interventions to promote hand washing or a hygiene promotion that included hand washing with no intervention to promote hand washing. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and methodological quality. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CI). MAIN RESULTS: Fourteen randomized controlled trials met the inclusion criteria. Eight trials were institution-based, five were community-based, and one was in a high-risk group (AIDS patients). Interventions promoting hand washing resulted in a 29% reduction in diarrhoea episodes in institutions in high-income countries (IRR 0.71, 95% CI 0.60 to 0.84; 7 trials) and a 31% reduction in such episodes in communities in low- or middle-income countries (IRR 0.69, 95% CI 0.55 to 0.87; 5 trials). AUTHORS' CONCLUSIONS: Hand washing can reduce diarrhoea episodes by about 30%. This significant reduction is comparable to the effect of providing clean water in low-income areas. However, trials with longer follow up and that test different methods of promoting hand washing are needed.

BACKGROUND: Immunisation is a powerful public health strategy for improving child survival, not only by directly combating key diseases that kill children but also by providing a platform for other health services. However, each year millions of children worldwide, mostly from low- and middle-income countries (LMICs), do not receive the full series of vaccines on their national routine immunisation schedule. This is an update of the Cochrane review published in 2011 and focuses on interventions for improving childhood immunisation coverage in LMICs. OBJECTIVES: To evaluate the effectiveness of intervention strategies to boost and sustain high childhood immunisation coverage in LMICs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2016, Issue 4, part of The Cochrane Library. www.cochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 12 May 2016); MEDLINE In-Process and Other Non-Indexed Citations, MEDLINE Daily and MEDLINE 1946 to Present, OvidSP (searched 12 May 2016); CINAHL 1981 to present, EbscoHost (searched 12 May 2016); Embase 1980 to 2014 Week 34, OvidSP (searched 2 September 2014); LILACS, VHL (searched 2 September 2014); Sociological Abstracts 1952 - current, ProQuest (searched 2 September 2014). We did a citation search for all included studies in Science Citation Index and Social Sciences Citation Index, 1975 to present; Emerging Sources Citation Index 2015 to present, ISI Web of Science (searched 2 July 2016). We also searched the two Trials Registries: ICTRP and ClinicalTrials.gov (searched 5 July 2016) SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCT), non-RCTs, controlled before-after studies, and interrupted time series conducted in LMICs involving children aged from birth to four years, caregivers, and healthcare providers. DATA COLLECTION AND ANALYSIS: We independently screened the search output, reviewed full texts of potentially eligible articles, assessed risk of bias, and extracted data in duplicate; resolving discrepancies by consensus. We then conducted random-effects meta-analyses and used GRADE to assess the certainty of evidence. MAIN RESULTS: Fourteen studies (10 cluster RCTs and four individual RCTs) met our inclusion criteria. These were conducted in Georgia (one study), Ghana (one study), Honduras (one study), India (two studies), Mali (one study), Mexico (one study), Nicaragua (one study), Nepal (one study), Pakistan (four studies), and Zimbabwe (one study). One study had an unclear risk of bias, and 13 had high risk of bias. The interventions evaluated in the studies included community-based health education (three studies), facility-based health education (three studies), household incentives (three studies), regular immunisation outreach sessions (one study), home visits (one study), supportive supervision (one study), information campaigns (one study), and integration of immunisation services with intermittent preventive treatment of malaria (one study).We found moderate-certainty evidence that health education at village meetings or at home probably improves coverage with three doses of diphtheria-tetanus-pertussis vaccines (DTP3: risk ratio (RR) 1.68, 95% confidence interval (CI) 1.09 to 2.59). We also found low-certainty evidence that facility-based health education plus redesigned vaccination reminder cards may improve DTP3 coverage (RR 1.50, 95% CI 1.21 to 1.87). Household monetary incentives may have little or no effect on full immunisation coverage (RR 1.05, 95% CI 0.90 to 1.23, low-certainty evidence). Regular immunisation outreach may improve full immunisation coverage (RR 3.09, 95% CI 1.69 to 5.67, low-certainty evidence) which may substantially improve if combined with household incentives (RR 6.66, 95% CI 3.93 to 11.28, low-certainty evidence). Home visits to identify non-vaccinated children and refer them to health clinics may improve uptake of three doses of oral polio vaccine (RR 1.22, 95% CI 1.07 to 1.39, low-certainty evidence). There was low-certainty evidence that integration of immunisation with other services may improve DTP3 coverage (RR 1.92, 95% CI 1.42 to 2.59). AUTHORS' CONCLUSIONS: Providing parents and other community members with information on immunisation, health education at facilities in combination with redesigned immunisation reminder cards, regular immunisation outreach with and without household incentives, home visits, and integration of immunisation with other services may improve childhood immunisation coverage in LMIC. Most of the evidence was of low certainty, which implies a high likelihood that the true effect of the interventions will be substantially different. There is thus a need for further well-conducted RCTs to assess the effects of interventions for improving childhood immunisation coverage in LMICs.

BACKGROUND: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

Purpose To investigate the inhibitive effect of gum arabic (GA) for the corrosion of aluminium in alkaline (NaOH) medium and determine its adsorption characteristics. The present work is another trial to find a cheap and environmentally safe inhibitor for aluminium corrosion. Design/methodology/approach The inhibition efficiency (%I) has been evaluated using the hydrogen evolution (via the gasometric assembly) and the thermometric methods at 30 and 40°C. The concentrations of GA (inhibitor) used were 0.1‐0.5 g/l and the concentrations of NaOH (the corrodent) were 0.1‐2.5 M. The mechanism of adsorption inhibition and type of adsorption isotherms were proposed from the trend of inhibition efficiency with temperature, E a , Δ G ads and Q ads values. Findings GA inhibited the corrosion of aluminium in NaOH solutions. The inhibition efficiency increased with increase in GA concentration and with increase in temperature. Phenomenon of chemical adsorption is proposed for the inhibition and the process followed the Langmuir and Freundlich adsorption isotherms. The results obtained in this study for the %I were comparable for the two methods used and were corroborated by kinetic and thermodynamic parameters evaluated from the experimental data. Research limitations/implications Further investigations involving electrochemical studies such as polarization method will enlighten more on the mechanistic aspect of the corrosion inhibition. Originality/value This paper provides new information on the possible application of GA as an environmentally friendly corrosion inhibitor even in highly aggressive alkaline environments. It has not been published elsewhere.

Abstract Background MicroRNAs (miRNAs) are 21~25-nucleotides (nt) long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi), depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs) inhibited the transcription of HIV-1. Results Here, we show the possibility that nef -derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA) that corresponded to a predicted nef miRNA (~25 nt, miR-N367) can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2). In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo . Conclusions These data suggest that nef /U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.

OBJECTIVE: To review the evidence on effectiveness of peridomestic space spraying of insecticides in reducing wild Aedes populations and interrupting dengue transmission. METHODS: Comprehensive literature search of MEDLINE, EMBASE, LILACS, Web of Science, WHOLIS, MedCarib and CENTRAL, and a manual search of reference lists from identified studies. Duplicates were removed and abstracts assessed for selection. All field evaluations of peridomestic space spraying targeting wild adult Aedes vectors in dengue endemic countries were included. Data were extracted, and the methodological quality of the studies was assessed independently by two reviewers. RESULTS: Fifteen studies met the inclusion criteria. Outcome measures were heterogeneous, foregoing the possibility of meta-analysis. Thirteen studies showed reductions in immature entomological indices that were not sustained for long periods. The remainder showed space spray interventions to be ineffective at reducing adult and/or immature entomological indices. Only one study measured human disease indicators, but its outcomes could not be directly attributed to space sprays alone. CONCLUSION: Although peridomestic space spraying is commonly applied by national dengue control programmes, there are very few studies evaluating the effectiveness of this intervention. There is no clear evidence for recommending peridomestic space spraying as a single, effective control intervention. Thus, peridomestic space spraying is more likely best applied as part of an integrated vector management strategy. The effectiveness of this intervention should be measured in terms of impact on both adult and immature mosquito populations, as well as on disease transmission.

Abstract AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca 2+ -impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.

BACKGROUND: In the absence of accessible, good quality eye health services and inclusive environments, vision loss can impact individuals, households and communities in many ways, including through increased poverty, reduced quality of life and reduced employment. We aimed to estimate the annual potential productivity losses associated with reduced employment due to blindness and moderate and severe vision impairment (MSVI) at a regional and global level. METHODS: We constructed a model using the most recent economic, demographic (2018) and prevalence (2020) data. Calculations were limited to the working age population (15-64 years) and presented in 2018 US Dollars purchasing power parity (ppp). Two separate models, using Gross Domestic Product (GDP) and Gross National Income (GNI), were calculated to maximise comparability with previous estimates. FINDINGS: We found that 160.7 million people with MSVI or blindness were within the working age and estimated that the overall relative reduction in employment by people with vision loss was 30.2%. Globally, using GDP we estimated that the annual cost of potential productivity losses of MSVI and blindness was $410.7 billion ppp (range $322.1 - $518.7 billion), or 0.3% of GDP. Using GNI, overall productivity losses were estimated at $408.5 billion ppp (range $320.4 - $515.9 billion), 0.5% lower than estimates using GDP. INTERPRETATION: These findings support the view that blindness and MSVI are associated with a large economic impact worldwide. Reducing and preventing vision loss and developing and implementing strategies to help visually impaired people to find and keep employment may result in significant productivity gains. FUNDING: Commission on Global Eye Health was supported by grants from The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity (GR001061), NIHR Moorfields Biomedical Research Centre, The Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The SEVA Foundation, The British Council for the Prevention of Blindness and Christian Blind Mission. The funders had no role in the design, conduct, data analysis of the study, or writing of the manuscript.

OBJECTIVE: To investigate the burden and causes of life-threatening maternal complications and the quality of emergency obstetric care in Nigerian public tertiary hospitals. DESIGN: Nationwide cross-sectional study. SETTING: Forty-two tertiary hospitals. POPULATION: Women admitted for pregnancy, childbirth and puerperal complications. METHODS: All cases of severe maternal outcome (SMO: maternal near-miss or maternal death) were prospectively identified using the WHO criteria over a 1-year period. MAIN OUTCOME MEASURES: Incidence and causes of SMO, health service events, case fatality rate, and mortality index (% of maternal death/SMO). RESULTS: Participating hospitals recorded 91 724 live births and 5910 stillbirths. A total of 2449 women had an SMO, including 1451 near-misses and 998 maternal deaths (2.7, 1.6 and 1.1% of live births, respectively). The majority (91.8%) of SMO cases were admitted in critical condition. Leading causes of SMO were pre-eclampsia/eclampsia (23.4%) and postpartum haemorrhage (14.4%). The overall mortality index for life-threatening conditions was 40.8%. For all SMOs, the median time between diagnosis and critical intervention was 60 minutes (IQR: 21-215 minutes) but in 21.9% of cases, it was over 4 hours. Late presentation (35.3%), lack of health insurance (17.5%) and non-availability of blood/blood products (12.7%) were the most frequent problems associated with deficiencies in care. CONCLUSIONS: Improving the chances of maternal survival would not only require timely application of life-saving interventions but also their safe, efficient and equitable use. Maternal mortality reduction strategies in Nigeria should address the deficiencies identified in tertiary hospital care and prioritise the prevention of severe complications at lower levels of care. TWEETABLE ABSTRACT: Of 998 maternal deaths and 1451 near-misses reported in a network of 42 Nigerian tertiary hospitals in 1 year.

In the present investigation, the concentration of heavy metals (As, Ba, Fe, Hg, Mn, Ni, Pb, Zn) in pond and stream water samples near abandoned barite mines have been studied. The main objective of study was to appraise the degree of contamination and human risk assessment due to barite mining. Results showed that the average concentrations of Fe, Hg and Pb were above the required standard. This indicates anthropogenic inputs from barite mining activities. The mean concentrations of Ba, Hg, Mn, Ni, Pb and Zn were higher in pond water compared to stream water. Contamination index and Nemerow pollution index indicated contamination at some mine sites, while human health risk assessment indicated unacceptable risk (hazard index (HI) values > 1) for non-carcinogenic adverse health effect. The cancer risk of being exposed to Arsenic by drinking water from these sources did not exceed the acceptable risk of 1:10,000 for regulatory purposes.