Evaluating insecticide-resistance in the malaria vector Anopheles gambiae and its implications for malaria transmission

Insecticide resistance, in the mosquito vector, threatens the efficacy of current methods to control malaria. Yet evidence of control failure due to insecticide resistance is sparse, despite over 50 years since resistance was identified in the mosquito. In this thesis, laboratory experiments with mosquitoes, as well as mathematical modelling, are used to improve our understanding of how insecticide resistance might impact malaria transmission. Firstly, demographic and environmental effects on the phenotypic expression of resistance are investigated. Decreasing expression of resistance with age and malaria infection, suggest resistance may not be as large a problem as once believed. Further factors that affect the phenotypic expression of resistance, such as infection by the microsporidian Vavria culicis and quantity of larval food, suggest that the phenotypic expression of resistance may even be manipulated to reduce its impact on disease transmission. Secondly, costs of resistance are explored as they may reduce the ability of a mosquito to transmit malaria. It is demonstrated that, under environmental stress from parasites, costs to longevity can be increased. Mosquito longevity is a key parameter in malaria transmission so any reduction in longevity, due to costs of resistance, will reduce the ability of the mosquito to transmit malaria. Finally, the thesis examines if the behavioural avoidance of insecticides can be changed through environmental manipulation. In summary, the phenotypic expression of resistance and the costs of resistance are two factors that will determine the threat insecticide-resistance poses to malaria control. It is demonstrated, in the laboratory, that these two factors can vary due to environmental and demographic factors, but to fully understand the threat of resistance these ideas have to be investigated in the field.Open Acces

Blocking the evolution of insecticide-resistant malaria vectors with a microsporidian

Finding a way to block the evolution insecticide resistance would be a major breakthrough for the control of malaria. We suggest that this may be possible by introducing a stress into mosquito populations that restores the sensitivity of genetically resistant mosquitoes and that decreases their longevity when they are not exposed to insecticide. We use a mathematical model to show that, despite the intense selection pressure imposed by insecticides, moderate levels of stress might tip the evolutionary balance between costs and benefits of resistance toward maintaining sensitivity. Our experimental work with the microsporidian parasite Vavraia culicis infecting two lines of resistant mosquitoes and a sensitive line suggests that it may indeed be possible to stress the mosquitoes in the required way. The mortality of resistant mosquitoes 24 h after exposure to the insecticide was up to 8.8 times higher in infected than in uninfected ones; if mosquitoes were not exposed to the insecticide, resistant mosquitoes infected by the microsporidian lived about half as long as uninfected ones and insecticide-sensitive mosquitoes (with or without the parasite). Our results suggest that biopesticides or other insecticides that interfere with the expression of resistance may help to manage insecticide resistance in programs of malaria control

Semi-field evaluation of freestanding transfluthrin passive emanators and the BG sentinel trap as a "push-pull control strategy" against Aedes aegypti mosquitoes

Spatial repellents that drive mosquitoes away from treated areas, and odour-baited traps, that attract and kill mosquitoes, can be combined and work synergistically in a push-pull system. Push-pull systems have been shown to reduce house entry and outdoor biting rates of malaria vectors and so have the potential to control other outdoor biting mosquitoes such as Aedes aegypti that transmit arboviral diseases. In this study, semi-field experiments were conducted to evaluate whether a push-pull system could be used to reduce bites from Aedes mosquitoes.; The push and pull under investigation consisted of two freestanding transfluthrin passive emanators (FTPE) and a BG sentinel trap (BGS) respectively. The FTPE contained hessian strips treated with 5.25 g of transfluthrin active ingredient. The efficacies of FTPE and BGS alone and in combination were evaluated by human landing catch in a large semi-field system in Tanzania. We also investigated the protection of FTPE over six months. The data were analyzed using generalized linear mixed models with binomial distribution.; Two FTPE had a protective efficacy (PE) of 61.2% (95% confidence interval (CI): 52.2-69.9%) against the human landing of Ae. aegypti. The BGS did not significantly reduce mosquito landings; the PE was 2.1% (95% CI: -2.9-7.2%). The push-pull provided a PE of 64.5% (95% CI: 59.1-69.9%). However, there was no significant difference in the PE between the push-pull and the two FTPE against Ae. aegypti (P = 0.30). The FTPE offered significant protection against Ae. aegypti at month three, with a PE of 46.4% (95% CI: 41.1-51.8%), but not at six months with a PE of 2.2% (95% CI: -9.0-14.0%).; The PE of the FTPE and the full push-pull are similar, indicative that bite prevention is primarily due to the activity of the FTPE. While these results are encouraging for the FTPE, further work is needed for a push-pull system to be recommended for Ae. aegypti control. The three-month protection against Ae. aegypti bites suggests that FTPE would be a useful additional control tool during dengue outbreaks, that does not require regular user compliance

The Lantern, 2020-2021

One Thousand and One is Never Enough • House on Hazel Ave. • Crooked Men at Crooked Alley • Home • Honeybee • The Witch\u27s Daughter • Traveling to Reyu • December 31st, 2019 • The Dominator Rolls the Dice Again • Red Flowers • Military Ball • Drowning in Color • Early Bird • Introspection • Hot Water • Reaching Into Space • Floating Marigolds Before COVID-19 • Smokestack 4 • Longing • His Fifth Year on Amstel Road • Wonderful Moments • Clean Glass • Betty, the Debutante • Teakettles Have it Easy • Fuimos, Somos y Seramos Parte de la Historia de la Isla • Kitchen Table • She Couldn\u27t • Cooling Down • Not so Precious Stones • Domestic Wild • Violet Eater • I Will be Sweet • Flavor of Life • Clogged Artery • All Twenty-Six • The Greatest • From Ashes of War to Golden Cities • A Good Thing • Introduction • Devotion • Life of the Gambler • Impressions: Or a Dining Table\u27s Soliloquy • Looking Glass • Montgomery Pie • Under the Hill • Paperback Lesbian • Girl With Pearl Earring • Your Mirror • Jacket • Illusions • Strawberry Girl (Raw Sugar, Shattered Glass) • I Don\u27t Jam With Instagram • The Morning After Saturday • A Brisk Monday Morning • Emergence • Politeness and Pattern Recognition • Douglas Adams\u27 Guide to Florida • A Love Story With Femininity • Roots • Dysmorphia IIIhttps://digitalcommons.ursinus.edu/lantern/1189/thumbnail.jp

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

Developing Mathematical Concepts for 5 - 6 Years Old Children with Different Diagnosed Developmental Disabilities

Darba nosaukums: “ Matemātisko priekšstatu veidošana 5 – 6 gadīgiem bērniem ar jauktiem attīstības traucējumiem“. Autore: Dace Kārkliņa Darba zinātniskā vadītāja: Doc., Dr. paed. Rasma Vīgante Darba apjoms: 66 lpp., 7 tabulas, 15 attēli, 37 literatūras avoti, 7 pielikumi. Pētījuma mērķis: izpētīt matemātisko priekšstatu veidošanas iespējas 5 –6 gadīgiem bērniem ar jauktiem attīstības traucējumiem. Pētījuma objekts: matemātisko priekšstatu veidošana. Pētījuma priekšmets: pielāgoti vingrinājumi matemātisko priekšstatu apguvei. Pētījuma metodes: 1)Pedagoģiskās un psiholoģiskās literatūras analīze; 2)Bērna attīstības vēstures analizēšana; 3)Pedagoģiskā novērošana; 4)Pārrunas. Pētījuma jautājums: kā bērniem ar jauktiem attīstības traucējumiem saprotami veidot matemātiskos priekšstatus? Teorētiskajā daļā tiek analizēta pedagoģiskā un psiholoģiskā literatūra, kas saistīta ar attīstības īpatnībām 5 – 6 gadīgiem bērniem ar jauktiem attīstības traucējumiem, izzinātas iespējas par matemātisko priekšstatu veidošanu un attīstīšanu. Pētījuma teorētiskā daļa balstās uz V. Avotiņa., S.Liepiņas., S.Tūbeles., G.Svences., J.Menča., R.Ukstiņas., I. Freimaņa., R. Vīgantes., M. Montesori un citu autoru atziņām par 5 – 6 gadīgu bērnu ar jauktiem attīstības traucējumiem attīstību un teorētisko skaidrojumu par matemātisko priekšstatu veidošanu. Praktiskajā daļā tiek piedāvāti un aprobēti vingrinājumi rotaļnodarbībām matemātisko priekšstatu veidošanai. Tiek veikta pedagoģiskā novērojuma laikā iegūto rezultātu analīze.The research papers title: “ Developing mathematical concepts for 5 - 6 years old children with different diagnosed developmental disabilities “. The author: Dace Kārkliņa The research papers supervisor: Doc., Dr. paed. Rasma Vīgante The research paper consists of: 66 pages, 7 tables, 15 pictures, 37 literature sources, appendices. The research aim: to explore opportunities of mathematical concepts for 5 - 6 years old children with different diagnosed developmental disabilities. The research object: mathematical concepts formation. The research subject: adapted exercises for mathematical concepts acquirement. The research methods: 1)Pedagogical and psychological literature analysis; 2)Analysis of the child’s development history; 3)Pedagogical observation; 4)Discussions. The research question: how understandably create mathematical concepts to children with different diagnosed developmental disabilities? In the theoretical part of the research pedagogical and psychological literature that is associated with development’s features for 5-6 year old children with different diagnosed developmental disabilities is analyzed, opportunities of mathematical concepts formation and development are explored. The researchs theoretical part is based on V. Avotiņš, S.Liepiņa, S.Tūbele, G.Svence, J.Mencis, R.Ukstiņa, I. Freimaņis, R.Vīgante, M.Montesori and the other authors’ knowledge of the development of 5-6 year old children with different diagnosed developmental disabilities and theoretical explanation of the mathematical concepts formation. In the practical part of the research, exercises for play lessons in order to create mathematical concepts are provided and approved. The analysis of the obtained results during the pedagogical observation is made