55 research outputs found
Impaired Wound Healing in Mouse Models of Diabetes Is Mediated by TNF-α Dysregulation and Associated With Enhanced Activation of Forkhead Box O1 (FOXO1)
Aims/hypothesis
The role of TNF-α in impaired wound healing in diabetes was examined by focusing on fibroblasts. Methods
Small excisional wounds were created in the db/db mice model of type 2 diabetes and normoglycaemic littermates, and in a streptozotocin-induced type 1 diabetes mouse model and control mice. Fibroblast apoptosis was measured by the TUNEL assay, proliferation by detection of proliferating cell nuclear antigen, and forkhead box O1 (FOXO1) activity by DNA binding and nuclear translocation. TNF-α was specifically inhibited by pegsunercept. Results
Diabetic wounds had increased TNF-α, fibroblast apoptosis, caspase-3/7 activity and activation of the pro-apoptotic transcription factor FOXO1, and decreased proliferating cell nuclear antigen positive fibroblasts (p \u3c 0.05). TNF-α inhibition improved healing in the diabetic mice and increased fibroblast density. This may be explained by a decrease in fibroblast apoptosis and increased proliferation when TNF-α was blocked (p \u3c 0.05). Although decreased fibroblast proliferation and enhanced FOXO1 activity were investigated in type 2 diabetes, they may also be implicated in type 1 diabetes. In vitro, TNF-α enhanced mRNA levels of gene sets related to apoptosis and Akt and p53 but not mitochondrial or cell-cycle pathways. FOXO1 small interfering RNA reduced gene sets that regulate apoptosis, Akt, mitochondrial and cell-cycle pathways. TNF-α also increased genes involved in inflammation, cytokine, Toll-like receptor and nuclear factor-kB pathways, which were significantly reduced by FOXO1 knockdown. Conclusions/interpretation
These studies indicate that TNF-α dysregulation in diabetic wounds impairs healing, which may involve enhanced fibroblast apoptosis and decreased proliferation. In vitro, TNF-α induced gene sets through FOXO1 that regulate a number of pathways that could influence inflammation and apoptosis
Evidence based assessment of scalability of agricultural technologies: The case of improved food legumes and small ruminant market sheds
United States Agency for International Developmen
Program assessment of efforts to improve the quality of postpartum counselling in health centers in Morogoro region, Tanzania
BACKGROUND: The postpartum period represents a critical window where many maternal and child deaths occur.
We assess the quality of postpartum care (PPC) as well as efforts to improve service delivery through additional
training and supervision in Health Centers (HCs) in Morogoro Region, Tanzania.
METHODS: Program implementers purposively selected nine program HCs for assessment with another nine HCs in
the region remaining as comparison sites in a non-randomized program evaluation. PPC quality was assessed by
examining structural inputs; provider and client profiles; processes (PNC counselling) and outcomes (patient
knowledge) through direct observations of equipment, supplies and infrastructure (n = 18) and PPC counselling (n
= 45); client exit interviews (n = 41); a provider survey (n = 62); and in-depth provider interviews (n = 10).
RESULTS: While physical infrastructure, equipment and supplies were comparable across study sites (with water and
electricity limitations), program areas had better availability of drugs and commodities. Overall, provider availability
was also similar across study sites, with 63% of HCs following staffing norms, 17% of Reproductive and Child Health
(RCH) providers absent and 14% of those providing PPC being unqualified to do so. In the program area, a median
of 4 of 10 RCH providers received training. Despite training and supervisory inputs to program area HCs, provider
and client knowledge of PPC was low and the content of PPC counseling provided limited to 3 of 80 PPC
messages in over half the consultations observed. Among women attending PPC, 29 (71%) had delivered in a
health facility and sought care a median of 13 days after delivery. Barriers to PPC care seeking included perceptions
that PPC was of limited benefit to women and was primarily about child health, geographic distance, gaps in the
continuity of care, and harsh facility treatment.
CONCLUSIONS: Program training and supervision activities had a modest effect on the quality of PPC. To achieve
broader transformation in PPC quality, client perceptions about the value of PPC need to be changed; the content
of recommended PPC messages reviewed along with the location for PPC services; gaps in the availability of
human resources addressed; and increased provider-client contact encouraged
Ensemble-based multi-filter feature selection method for DDoS detection in cloud computing
Widespread adoption of cloud computing has increased the attractiveness of such services to cybercriminals.
Distributed denial of service (DDoS) attacks targeting the cloud’s bandwidth, services and resources to render the
cloud unavailable to both cloud providers, and users are a common form of attacks. In recent times, feature
selection has been identified as a pre-processing phase in cloud DDoS attack defence which can potentially
increase classification accuracy and reduce computational complexity by identifying important features from the
original dataset during supervised learning. In this work, we propose an ensemble-based multi-filter feature
selection method that combines the output of four filter methods to achieve an optimum selection. We then
perform an extensive experimental evaluation of our proposed method using intrusion detection benchmark
dataset, NSL-KDD and decision tree classifier. The findings show that our proposed method can effectively reduce
the number of features from 41 to 13 and has a high detection rate and classification accuracy when compared to
other classification techniques
Routine health management information system data in Ethiopia: consistency, trends, and challenges.
Background: Ethiopia is investing in the routine Health Management Information System. Improved routine data are needed for decision-making in the health sector. Objective: To analyse the quality of the routine Health Management Information System data and triangulate with other sources, such as the Demographic and Health Surveys. Methods: We analysed national Health Management Information System data on 19 indicators of maternal health, neonatal survival, immunization, child nutrition, malaria, and tuberculosis over the 2012-2018 time period. The analyses were conducted by 38 analysts from the Ministry of Health, Ethiopia, and two government agencies who participated in the Operational Research and Coaching for Analysts (ORCA) project between June 2018 and June 2020. Using a World Health Organization Data Quality Review toolkit, we assessed indicator definitions, completeness, internal consistency over time and between related indicators, and external consistency compared with other data sources. Results: Several services reported coverage of above 100%. For many indicators, denominators were based on poor-quality population data estimates. Data on individual vaccinations had relatively good internal consistency. In contrast, there was low external consistency for data on fully vaccinated children, with the routine Health Management Information System showing 89% coverage but the Demographic and Health Survey estimate at 39%. Maternal health indicators displayed increasing coverage over time. Indicators on child nutrition, malaria, and tuberculosis were less consistent. Data on neonatal mortality were incomplete and operationalised as mortality on day 0-6. Our comparisons with survey and population projections indicated that one in eight early neonatal deaths were reported in the routine Health Management Information System. Data quality varied between regions. Conclusions: The quality of routine data gathered in the health system needs further attention. We suggest regular triangulation with data from other sources. We recommend addressing the denominator issues, reducing the complexity of indicators, and aligning indicators to international definitions
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Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation
Willingness to pay for Drought Tolerance (DT) in Maize in Communal Areas of Zimbabwe
This study aimed at estimating the implicit prices farmers are willing to pay (WTP) for maize traits with deliberate focus on drought tolerance. Using choice experiment, we generated 12600 observations from a random sample of 1400 households in communal areas within 14 districts of Zimbabwe. Taste parameters and heterogeneities (scale and residual taste) were estimated using the generalized multinomial logit model (G-MNL) and its different versions. Drought tolerance, grain yield, large grain size, covered cob tip, big cob and semi flint texture were the most preferred traits by rural Zimbabweans. The WTP values were estimated using the WTP space approach. Sample farmers are, for example, willing to pay a premium for drought tolerance that is 1.75 times the amount they are willing to pay for an increase of 1 ton in grain yield per acre, 8.3 times the value they attach for a change from small to big cob size, and 14.7 times the willingness to pay for semi-flint texture over dent texture of maize. The uncertainty that DT might not be appealing to poor farmers as much as some other technologies can only be cleared only if the promotion of DT materials is done in the right manner and to the right farm community. Innovative ways of promoting DT maize vis-à-vis creating awareness in contextual understanding of drought and drought risk shall be employed to enhance adoption of new DT maize varieties by risk prone farming communities. Given the high level of rural literacy and the high rate of adoption of improved maize in Zimbabwe, trait based promotion and marketing of varieties would be the right strategy
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