ABSTRACT
Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.
Subject(s)
Genome-Wide Association Study , Glaucoma, Open-Angle , Humans , Genetic Predisposition to Disease , Glaucoma, Open-Angle/genetics , Black People/genetics , Polymorphism, Single Nucleotide/geneticsABSTRACT
BACKGROUND: Using tailored mobile health interventions to improve global vascular risk awareness and control is yet to be investigated for primary stroke prevention in Africa. METHODS: This 2-arm pilot randomized controlled trial involved 100 stroke-free adults with at least 2 vascular risk factors for stroke. Eligible participants were assigned randomly to a control arm offering 1-time counseling (n=50) or a 2-month educational intervention arm (n=50) comprising a stroke video and riskometer app aimed at improving stroke risk factor awareness and health-seeking behavioral modification to control total vascular risk. Reduction in total stroke risk score was the primary outcome while feasibility and process measures were secondary outcomes. RESULTS: All enrolled participants completed the 2-month follow-up (retention rate=100%). The mean (SD) age of participants was 59.5 (±12.5) years, 38% were males. The mean change in stroke risk score at 2 months was -11.9% (±14.2) in the intervention arm versus -1.2% (±9.1) in the control arm, P=0.0001. Stroke risk awareness improved by 16.1% (±24.7) in the intervention arm versus 8.9% (±24.7) in the control arm, P=0.08. The intervention arm had 11.1 mm Hg reduction in systolic blood pressure compared with 4.8 mm Hg reduction in the control arm. CONCLUSIONS: The intervention demonstrated a positive signal of effect over a 2-month period. A definitive clinical trial with a longer duration of follow-up is warranted on the premise of these promising findings from this pilot randomized clinical trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05619406.
Subject(s)
Stroke , Male , Adult , Humans , Middle Aged , Aged , Female , Pilot Projects , Ghana/epidemiology , Nigeria/epidemiology , Stroke/epidemiology , Stroke/prevention & control , Stroke/complications , Risk Reduction BehaviorABSTRACT
BACKGROUND: As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research. METHODS: SIREN is a transnational, multicentre, hospital and community-based study involving 3,000 cases and 3,000 controls recruited from 8 sites in Ghana and Nigeria. Cases will be hospital-based patients with first stroke within 10 days of onset in whom neurovascular imaging will be performed. Etiological and topographical stroke subtypes will be documented for all cases. Controls will be hospital- and community-based participants, matched to cases on the basis of gender, ethnicity, and age (±5 years). Information will be collected on known and proposed emerging risk factors for stroke. STUDY SIGNIFICANCE: SIREN is the largest study of stroke in Africa to date. It is anticipated that it will shed light on the phenotypic characteristics and risk factors of stroke and ultimately provide evidence base for strategic interventions to curtail the burgeoning burden of stroke on the sub-continent.
Subject(s)
Phenotype , Stroke/classification , Stroke/etiology , Adult , Case-Control Studies , Clinical Protocols , Follow-Up Studies , Ghana/epidemiology , Humans , Nigeria/epidemiology , Research Design , Risk Factors , Stroke/epidemiologyABSTRACT
Hepatitis B and C have been identified as major causes of Transfusion transmitted infections, in Nigeria. Our objective was to determine the prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) in prospective blood donors in Abeokuta, Nigeria. 305 blood donors were screened for the presence of Hepatitis B virus surface antigen (HBsAg) and HCV using a rapid immunochromatographic kit (DiaSpot®). Demographic information was also collected. Males constituted 96.4%, singles were the majority with 65%. Prevalence of HBsAg was 9.8%, HCV 1.3%, and dual positivity 0.3%. Prevalence of HBsAg and HCV among males was 10.2% and 1.4%, while females recorded 0.0% for HCV and HBsAg. Dual positivity was recorded in a male (0.33%). Analysis of the study variables revealed that only educational status was statistically associated with positivity of HBsAg [Formula: see text], HCV prevalence was highest in the illiterate group it was not statistically significant (P > 0.05). We report the prevalence rates of anti-HCV Ab and HBsAg in blood donors from Ogun State, Nigeria. Our results reveals higher rate of HBsAg and evidence of co-infection with both viruses, illiteracy was the only variable associated with HBV infection. We advocate for the inclusion of anti-HBc or HBeAg in donor screening in our environment.
Subject(s)
Hepatitis B Surface Antigens/blood , Hepatitis C Antibodies/blood , Cross-Sectional Studies , Female , Hepatitis B Surface Antigens/immunology , Hepatitis C Antibodies/immunology , Humans , Male , Nigeria/epidemiology , Prospective Studies , Seroepidemiologic StudiesABSTRACT
This study examined if disclosure to their spouses by married women living with HIV/AIDS resulted in conflicts. Fifty-seven women completed a questionnaire on conflict indicators. While 93% disclosed their status within 6 months of diagnosis, 12.3% did so through a third party. More than thirty-six percent (36.8%) confirmed that disclosure led to conflict. Although 19.3% had their conflicts resolved through a third party, 10% suffered separation. Marital status and fear of stigma significantly influence time to disclose (p <.01 and p <.05), while type of marriage strongly influences whether status will be disclosed (p <.01). Programs for women with HIV should consider conflicts that may arise from disclosure.
Subject(s)
HIV Seropositivity/psychology , Self Disclosure , Spouses , Truth Disclosure , Violence , Adult , Fear , Female , Heterosexuality , Humans , Male , Marriage , Middle Aged , Nigeria , Social Stigma , Surveys and QuestionnairesABSTRACT
BACKGROUND: The use of genetically modified mosquitoes (GMMs) for the control of malaria and other mosquito-borne diseases has been proposed in malaria-endemic countries, such as Nigeria, which has the largest burden in Africa. Scientists are major stakeholders whose opinions and perceptions can adversely affect the success of the trials of GMMs if they are not involved early. Unfortunately, information on the awareness of Nigerians scientists and their overall perception of the GMMs is practically non-existent in the literature. Therefore, this study aimed at understanding how receptive Nigerian scientists are to a potential release of GMMs for the control of malaria. METHODS: The sample consisted of 164 scientists selected from academic and research institutions in Nigeria. Data were collected from participants using a semi-structured, self-administered questionnaire. Questions were asked about the cause and prevention of malaria, genetic modification and biotechnology. Specific questions on perception and acceptable conditions for the potential release of GM mosquitoes in Nigeria were also covered. RESULTS: All participants cited mosquitoes as one of several causes of malaria and used various methods for household control of mosquitoes. The main concerns expressed by the scientists were that GMMs can spread in an uncontrolled way beyond their release sites (89%) and will mate with other mosquito species to produce hybrids with unknown consequences (94.5%). Most participants (92.7%) agreed that it was important that before approving the release of GMMs in Nigeria, there had to be evidence of contingency measures available to remove the GMMs should a hazard become evident during the course of the release. In general, a majority (83.5%) of scientists who participated in this study were sceptical about a potential release in Nigeria, while 16.5% of the participants were in support. CONCLUSIONS: Although a majority of the participants are sceptical about GMMs generally, most encourage the use of genetic modification techniques to make mosquitoes incapable of spreading diseases provided that there are contingency measures to remove GMMs if a hazard becomes evident during the course of the release.
Subject(s)
Animals, Genetically Modified/psychology , Attitude , Culicidae , Insect Vectors , Mosquito Control/methods , Perception , Adult , Animals , Animals, Genetically Modified/genetics , Culicidae/genetics , Female , Humans , Insect Vectors/genetics , Malaria/prevention & control , Male , Middle Aged , Nigeria , Surveys and QuestionnairesABSTRACT
BACKGROUND: Prediction algorithms/models are viable methods for identifying individuals at high risk of stroke across diverse populations for timely intervention. However, evidence summarizing the performance of these models is limited. This study examined the performance and weaknesses of existing stroke risk-score-prediction models (SRSMs) and whether performance varied by population and region. METHODS: PubMed, EMBASE, and Web of Science were searched for articles on SRSMs from the earliest records until February 2022. The Prediction Model Risk of Bias Assessment Tool was used to assess the quality of eligible articles. The performance of the SRSMs was assessed by meta-analyzing C-statistics (0 and 1) estimates from identified studies to determine the overall pooled C-statistics by fitting a linear restricted maximum likelihood in a random effect model. RESULTS: Overall, 17 articles (cohort study = 15, nested case-control study = 2) comprising 739,134 stroke cases from 6,396,594 participants from diverse populations/regions (Asia; n = 8, United States; n = 3, and Europe and the United Kingdom; n = 6) were eligible for inclusion. The overall pooled c-statistics of SRSMs was 0.78 (95%CI: 0.75, 0.80; I2 = 99.9%), with most SRSMs developed using cohort studies; 0.78 (95%CI: 0.75, 0.80; I2 = 99.9%). The subgroup analyses by geographical region: Asia [0.81 (95%CI: 0.79, 0.83; I2 = 99.8%)], Europe and the United Kingdom [0.76 (95%CI: 0.69, 0.83; I2 = 99.9%)] and the United States only [0.75 (95%CI: 0.72, 0.78; I2 = 73.5%)] revealed relatively indifferent performances of SRSMs. CONCLUSION: SRSM performance varied widely, and the pooled c-statistics of SRSMs suggested a fair predictive performance, with very few SRSMs validated in independent population group(s) from diverse world regions.
Subject(s)
Stroke , Humans , Risk Assessment/methods , Stroke/epidemiology , Stroke/diagnosisABSTRACT
OBJECTIVES: To explore the prevalence and risk factors of obesity among older adults from low- and middle-income countries (LMICs). METHODS: This is a secondary analysis of data obtained from the SIREN study through in-person interviews and measurements from healthy stroke-free older adults (≥60 years). Overweight/obesity was defined as body mass index ≥25 kg/m2. Abdominal obesity was defined as waist-to-hip ratio (WHR) of >0.90 for males and >0.85/females or waist circumference (WC) of >102 cm for males/>88 cm for females. Adjusted odds ratio (aORs) with 95% confidence interval (CIs) of the relationship between obesity and sociodemographic factors were assessed at P < 0.05. RESULTS: Overall, 47.5% of participants were overweight/obese, 76.6% had a larger than recommended WHR, and 54.4% had a larger than recommended WC. Abdominal obesity (WC; aOR: 9.43, CI: 6.99-12.50), being a Nigerian (aOR: 0.55; CI: 0.42-0.72), living in an urban setting (aOR: 1.92; CI: 1.49-2.46), earning >$100/month (aOR: 1.53; CI: 1.19-1.96), and having formal education (aOR: 1.42; CI: 1.08-1.87) were associated with overweight/obesity. CONCLUSION: Living in urban settings, earning a higher income, and having a formal education were associated with a higher odds of obesity among older adults from LMICs.
Subject(s)
Obesity, Abdominal , Overweight , Male , Female , Humans , Aged , Overweight/epidemiology , Obesity, Abdominal/epidemiology , Independent Living , Nigeria/epidemiology , Ghana/epidemiology , Obesity/epidemiology , Risk Factors , Body Mass IndexABSTRACT
BACKGROUND: The relationship of diet with stroke risk among Africans is not well understood. AIM: The aim of this study was to investigate the association between dietary patterns and stroke risk among West Africans. METHODS: In this multi-center case-control study, 3684 stroke patients matched (for age and sex) with 3684 healthy controls were recruited from Nigeria and Ghana. Food consumption was assessed using a food frequency questionnaire, and dietary patterns were summarized using principal component analysis. Stroke was defined using predefined criteria primarily on clinical evaluation following standard guidelines. Conditional logistic regression was applied to compute odds ratio (OR) and 95% confidence interval (CI) for stroke risk by tertiles of dietary patterns adjusting for relevant confounders. RESULTS: Overall, mean age was 59.0 ± 13.9 years, and 3992 (54.2%) were males. Seven dietary patterns were identified. Multivariable-adjusted OR (95% CI) for risk of stroke by second and third tertiles (using the lowest and first tertile as reference) of dietary patterns was 1.65 (1.43, 1.90) and 1.74 (1.51, 2.02), for "poultry product and organ meat"; 1.69 (1.47, 1.96) and 1.51 (1.31, 1.75) for "red meat"; 1.07 (0.92, 1.23) and 1.21 (1.04, 1.40) for "fried foods and sweetened drinks"; 0.69 (0.60, 0.80) and 0.45 (0.39, 0.53) for "vegetables"; 0.84 (0.72, 0.97) and 0.81 (0.70, 0.93) for "whole-grain and fruit drinks"; and 0.97 (0.84, 1.12) and 0.85 (0.73, 0.98) for "fruits" respectively (p < 0.05). CONCLUSION: These data suggest that plant-based diets are associated with a lower risk of stroke and might be a beneficial dietary recommendation for the primary prevention of stroke among Africans.
Subject(s)
African People , Stroke , Male , Humans , Middle Aged , Aged , Female , Case-Control Studies , Feeding Behavior , Stroke/epidemiology , Diet , Fruit , Risk FactorsABSTRACT
BACKGROUND: This study aimed to develop a risk-scoring model for hypertension among Africans. METHODS: In this study, 4413 stroke-free controls were used to develop the risk-scoring model for hypertension. Logistic regression models were applied to 13 risk factors. We randomly split the dataset into training and testing data at a ratio of 80:20. Constant and standardized weights were assigned to factors significantly associated with hypertension in the regression model to develop a probability risk score on a scale of 0 to 1 using a logistic regression model. The model accuracy was assessed to estimate the cutoff score for discriminating hypertensives. RESULTS: Mean age was 59.9±13.3 years, 56.0% were hypertensives, and 8 factors, including diabetes, age ≥65 years, higher waist circumference, (BMI) ≥30 kg/m2, lack of formal education, living in urban residence, family history of cardiovascular diseases, and dyslipidemia use were associated with hypertension. Cohen κ was maximal at ≥0.28, and a total probability risk score of ≥0.60 was adopted for both statistical weighting for risk quantification of hypertension in both datasets. The probability risk score presented a good performance-receiver operating characteristic: 64% (95% CI, 61.0-68.0), a sensitivity of 55.1%, specificity of 71.5%, positive predicted value of 70.9%, and negative predicted value of 55.8%, in the test dataset. Similarly, decision tree had a predictive accuracy of 67.7% (95% CI, 66.1-69.3) for the training set and 64.6% (95% CI, 61.0-68.0) for the testing dataset. CONCLUSIONS: The novel risk-scoring model discriminated hypertensives with good accuracy and will be helpful in the early identification of community-based Africans vulnerable to hypertension for its primary prevention.
Subject(s)
Cardiovascular Diseases , Hypertension , Humans , Middle Aged , Aged , African People , Hypertension/diagnosis , Hypertension/epidemiology , Risk Factors , Risk AssessmentABSTRACT
BACKGROUND: Every minute, six indigenous Africans develop new strokes. Patient-level and system-level contributors to early stroke fatality in this region are yet to be delineated. We aimed to identify and quantify the contributions of patient-level and system-level determinants of inpatient stroke fatality across 16 hospitals in Ghana and Nigeria. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a multicentre study involving 16 sites in Ghana and Nigeria. Cases include adults (aged ≥18 years) with clinical and radiological evidence of an acute stroke. Data on stroke services and resources available at each study site were collected and analysed as system-level factors. A host of demographic and clinical variables of cases were analysed as patient-level factors. A mixed effect log-binomial model including both patient-level and system-level covariates was fitted. Results are presented as adjusted risk ratios (aRRs) with respective 95% CIs. FINDINGS: Overall, 814 (21·8%) of the 3739 patients admitted with stroke died as inpatients: 476 (18·1%) of 2635 with ischaemic stroke and 338 (30·6%) of 1104 with intracerebral haemorrhage. The variability in the odds of stroke fatality that could be attributed to the system-level factors across study sites assessed using model intracluster correlation coefficient was substantial at 7·3% (above a 5% threshold). Stroke units were available at only five of 16 centres. The aRRs of six patient-level factors associated with stroke fatality were: low vegetable consumption, 1·19 (95% CI 1·07-1·33); systolic blood pressure, 1·02 (1·01-1·04) for each 10 mm Hg rise; stroke lesion volume more than 30 cm3, 1·48 (1·22-1·79); National Institutes of Health Stroke Scale (NIHSS) score, 1·20 (1·13-1·26) for each 5-unit rise; elevated intracranial pressure, 1·75 (1·31-2·33); and aspiration pneumonia, 1·79 (1·16-2·77). INTERPRETATION: Studies are needed to assess the efficacy of interventions targeting patient-level factors such as aspiration pneumonia in reducing acute stroke fatality in this region. Policy directives to improve stroke unit access are warranted. FUNDING: US National Institutes of Health. TRANSLATIONS: For the Twi, Yoruba and Hausa translations of the abstract see Supplementary Materials section.
Subject(s)
Brain Ischemia , Pneumonia, Aspiration , Stroke , Adult , Humans , Adolescent , Prospective Studies , Nigeria/epidemiology , Ghana/epidemiology , Hospitals , Pneumonia, Aspiration/complicationsABSTRACT
Hypertension is one of the most important risk factors for stroke and cardiovascular diseases (CVD) globally. Understanding risk factors for hypertension among individuals with matching characteristics with stroke patients may inform primordial/primary prevention of hypertension and stroke among them. This study identified the risk factors for hypertension among community-dwelling stroke-free population in Ghana and Nigeria. Data for 4267 community-dwelling stroke-free controls subjects in the Stroke Investigative Research and Education Network (SIREN) study in Nigeria and Ghana were used. Participants were comprehensively assessed for sociodemographic, lifestyle and metabolic factors using standard methods. Hypertension was defined as a previous diagnosis by a health professional or use of an anti-hypertensive drug or mean systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Logistic regression analysis was used to estimate adjusted odds ratios (aOR) of hypertension and their 95% confidence intervals (CI) at p < .05. Overall, 56.7% of the participants were hypertensive with a higher proportion among respondents aged ≥60 years (53.0%). Factors including physical inactivity (aOR: 9.09; 95% CI: 4.03 to 20.53, p < .0001), diabetes (aOR: 2.70; CI: 1.91 to 3.82, p < .0001), being ≥60 years (aOR: 2.22; 95% CI: 1.78 to 2.77, p < .0001), and family history of CVD (aOR 2.02; CI: 1.59 to 2.56, p < .0001) were associated with increased aOR of hypertension. Lifestyle factors were associated with hypertension in the current population of community-dwelling stroke-free controls in west Africa. Community-oriented interventions to address sedentary lifestyles may benefit this population and reduce/prevent hypertension and stroke among them.
Subject(s)
Hypertension , Stroke , Ghana/epidemiology , Humans , Hypertension/epidemiology , Nigeria , Risk Factors , Stroke/epidemiologyABSTRACT
Hypertension and obesity are the most important modifiable risk factors for cardiovascular diseases, but their association is not well characterized in Africa. We investigated regional patterns and association of obesity with hypertension among 30 044 continental Africans. We harmonized data on hypertension (defined as previous diagnosis/use of antihypertensive drugs or blood pressure [BP]≥140/90 mmHg/BP≥130/80 mmHg) and obesity from 30 044 individuals in the Cardiovascular H3Africa Innovation Resource across 13 African countries. We analyzed data from population-based controls and the Entire Harmonized Dataset. Age-adjusted and crude proportions of hypertension were compared regionally, across sex, and between hypertension definitions. Logit generalized estimating equation was used to determine the independent association of obesity with hypertension (P value <5%). Participants were 56% women; with mean age 48.5±12.0 years. Crude proportions of hypertension (at BP≥140/90 mmHg) were 47.9% (95% CI, 47.4-48.5) for Entire Harmonized Dataset and 42.0% (41.1-42.7) for population-based controls and were significantly higher for the 130/80 mm Hg threshold at 59.3% (58.7-59.9) in population-based controls. The age-adjusted proportion of hypertension at BP≥140/90 mmHg was the highest among men (33.8% [32.1-35.6]), in western Africa (34.7% [33.3-36.2]), and in obese individuals (43.6%; 40.3-47.2). Obesity was independently associated with hypertension in population-based controls (adjusted odds ratio, 2.5 [2.3-2.7]) and odds of hypertension in obesity increased with increasing age from 2.0 (1.7-2.3) in younger age to 8.8 (7.4-10.3) in older age. Hypertension is common across multiple countries in Africa with 11.9% to 51.7% having BP≥140/90 mmHg and 39.5% to 69.4% with BP≥130/80 mmHg. Obese Africans were more than twice as likely to be hypertensive and the odds increased with increasing age.
Subject(s)
Hypertension/epidemiology , Obesity/epidemiology , Adult , Africa/epidemiology , Aged , Antihypertensive Agents/therapeutic use , Body Mass Index , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Hypertension/drug therapy , Male , Middle Aged , Overweight/epidemiology , Prevalence , Risk FactorsABSTRACT
Though the SDQ has been used in selected studies in Nigeria, its theoretical structure has not been fully and appropriately investigated in the setting. The present study employs Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) to investigate the theoretical structure of the self-reported version of the SDQ in a sample of adolescents in Benue state, Nigeria. A total of 1,244 adolescents from different categories of secondary schools in Makurdi and Vandekya Local government areas of Benue state participated in the study. Preliminary data analyses were performed using descriptive statistics while the theoretical structure of the SDQ was assessed using EFA and CFA. Model fits were assessed using Chi-square test and other fit indices at 5% significance level. Participants were 14.19±2.45 (Vandekya) and 14.19±2.45 (Makurdi) years old. Results of the EFA and CFA revealed a 3-factor oblique model as the best model for the sample of adolescents studied (χ2/df =2.20, p<0.001) with all fit indices yielding better results. A correlated 3-factor model fits the present data better than the 5-factor theoretical model of the SDQ. The use of the original 5-factor model of the SDQ in the present setting should be interpreted with caution.
ABSTRACT
Introduction. Distribution of Affordable Medicine Facility-malaria Artemisinin Combination Therapies (AMFm-ACTs) started in Nigeria in 2011, but its use at community level has not been documented. Methods. Four hundred seventy-eight caregivers whose under-five children had fever within two weeks prior to the survey were selected using cluster sampling technique. Information on sociodemographic characteristics, treatment seeking for malaria, and awareness and use of AMFm-ACTs was collected using an interviewer administered questionnaire. Result. More than half of the respondents (51.2%) bought AMFm-ACTs without prescription. Awareness of AMFm was low as only 9.1% has heard about the programme. Overall, 29.2% used AMFm-ACTs as their first line choice of antimalarial drug. On bivariate analysis age, group (25-34 years), public servants, respondents with tertiary education, respondents with high socioeconomic status, respondents with poor knowledge of symptoms of malaria, awareness of AMFm-ACTs, availability of AMFm-ACTs, and sources of drug were significantly associated with utilization of AMFm-ACTs (P < 0.05). Logistic regression demonstrated that only people who were aware of AMFM-ACTs predicted its use (AOR: 0.073; CI: 0.032-0.166; P < 0.001). Conclusion. Interventions which targeted at raising awareness of AMFm-ACTs among people at risk of malaria are advocated for implementation.