8,805 research outputs found

    Small newborns in post-conflict Northern Uganda: Burden and interventions for improved outcomes

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    Introduction: A small newborn can be the result of either a low birthweight (LBW), or a preterm birth (PB), or both. LBW can be due to either a preterm appropriate-for gestational-age (preterm-AGA), or a term small-for-gestational age (term-SGA) or intrauterine growth restriction (IUGR). An IUGR is a limited in-utero foetal growth rates or foetal weight < 10th percentile. Small newborns have an increased risk of dying, particularly in low-resource settings. We set out to assess the burden, the modifiable risk factors and health outcomes of small newborns in the post-conflict Northern Ugandan district of Lira. In addition, we studied the use of video-debriefing when training health staff in Helping Babies Breathe. Subjects and methods: In 2018-19, we conducted a community-based cohort study on 1556 mother-infant dyads, nested within a cluster randomized trial. In our cohort study, we estimated the incidence and risk factors for LBW and PB and the association of LBW with severe outcomes. We explored the prevalence of and factors associated with neonatal hypoglycaemia, as well as any association between neonatal death and hypoglycaemia. In addition, we conducted a cluster randomized trial to compare Helping Babies Breathe (HBB) training in combination with video debriefing to the traditional HBB training alone on the attainment and retention of health worker neonatal resuscitation competency. Results: The incidence of LBW and PB in our cohort was lower than the global estimates, 7.3% and 5.0%, respectively. Intermittent preventive treatment for malaria was associated with a reduced risk of LBW. HIV infection was associated with an increased risk of both LBW and PB, while maternal formal education (schooling) of ≄7 years was associated with a reduced risk of LBW and PB. The proportions of neonatal deaths were many-folds higher among LBW infants compared to their non-LBW counterparts. The proportion of neonatal deaths among LBW was 103/1000 live births compared to 5/1000 among the non-LBW. The prevalence of neonatal hypoglycaemia in our cohort was 2.5%. LBW and PB each independently were associated with an increased risk of neonatal hypoglycaemia. Neonatal hypoglycaemia was associated with an increased risk of hospitalisation and severe outcomes. We demonstrated that neonatal resuscitation training with video debriefing, improved competence attainment and retention among health workers, compared to traditional HBB training alone. Conclusion: In northern Uganda, small infants still have a many-fold higher risk of dying compared to normal infants. In addition, small infants are also at more risk of neonatal hypoglycaemia compared to normal infants. Efforts are needed to secure essential newborn care, should we reach the target of Sustainable Development Goal number 3.2 of reducing infant mortality to less than 12/1000 live births by 2030

    AnuĂĄrio cientĂ­fico da Escola Superior de Tecnologia da SaĂșde de Lisboa - 2021

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    É com grande prazer que apresentamos a mais recente edição (a 11.ÂȘ) do AnuĂĄrio CientĂ­fico da Escola Superior de Tecnologia da SaĂșde de Lisboa. Como instituição de ensino superior, temos o compromisso de promover e incentivar a pesquisa cientĂ­fica em todas as ĂĄreas do conhecimento que contemplam a nossa missĂŁo. Esta publicação tem como objetivo divulgar toda a produção cientĂ­fica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal nĂŁo Docente da ESTeSL durante 2021. Este AnuĂĄrio Ă©, assim, o reflexo do trabalho ĂĄrduo e dedicado da nossa comunidade, que se empenhou na produção de conteĂșdo cientĂ­fico de elevada qualidade e partilhada com a Sociedade na forma de livros, capĂ­tulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunicaçÔes orais e pĂłsteres, bem como resultado dos trabalhos de 1Âș e 2Âș ciclo. Com isto, o conteĂșdo desta publicação abrange uma ampla variedade de tĂłpicos, desde temas mais fundamentais atĂ© estudos de aplicação prĂĄtica em contextos especĂ­ficos de SaĂșde, refletindo desta forma a pluralidade e diversidade de ĂĄreas que definem, e tornam Ășnica, a ESTeSL. Acreditamos que a investigação e pesquisa cientĂ­fica Ă© um eixo fundamental para o desenvolvimento da sociedade e Ă© por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e prĂĄtica baseada na evidĂȘncia desde o inĂ­cio dos seus estudos na ESTeSL. Esta publicação Ă© um exemplo do sucesso desses esforços, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade cientĂ­fica e o pĂșblico em geral. Esperamos que este AnuĂĄrio inspire e motive outros estudantes, profissionais de saĂșde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avanço da ciĂȘncia e da tecnologia no corpo de conhecimento prĂłprio das ĂĄreas que compĂ”e a ESTeSL. Agradecemos a todos os envolvidos na produção deste anuĂĄrio e desejamos uma leitura inspiradora e agradĂĄvel.info:eu-repo/semantics/publishedVersio

    Mathematical models to evaluate the impact of increasing serotype coverage in pneumococcal conjugate vaccines

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    Of over 100 serotypes of Streptococcus pneumoniae, only 7 were included in the first pneumo- coccal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation. This thesis has four aims. First, to explore the limitations and assumptions of published pneu- mococcal models and the implications for future vaccine formulation and policy. Second, to conduct a trend analysis assembling all the available evidence for serotype replacement in Europe, North America and Australia to characterise invasive pneumococcal disease (IPD) caused by vaccine-type (VT) and non-vaccine-types (NVT) serotypes. The motivation behind this is to assess the patterns of relative abundance in IPD cases pre- and post-vaccination, to examine country-level differences in relation to the vaccines employed over time since introduction, and to assess the growth of the replacement serotypes in comparison with the serotypes targeted by the vaccine. The third aim is to use a Bayesian framework to estimate serotype-specific invasiveness, i.e. the rate of invasive disease given carriage. This is useful for dynamic transmission modelling, as transmission is through carriage but a majority of serotype-specific pneumococcal data lies in active disease surveillance. This is also helpful to address whether serotype replacement reflects serotypes that are more invasive or whether serotypes in a specific location are equally more invasive than in other locations. Finally, the last aim of this thesis is to estimate the epidemiological and economic impact of increas- ing serotype coverage in PCVs using a dynamic transmission model. Together, the results highlight that though there are key parameter uncertainties that merit further exploration, divergence in serotype replacement and inconsistencies in invasiveness on a country-level may make a universal PCV suboptimal.Open Acces

    RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinson’s disease targeting RNA/HuR complexes

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    MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy. HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinson’s disease (PD). PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies. In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD. To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells. To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3’ untranslated region (3’-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression. In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies

    Increased lifetime of Organic Photovoltaics (OPVs) and the impact of degradation, efficiency and costs in the LCOE of Emerging PVs

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    Emerging photovoltaic (PV) technologies such as organic photovoltaics (OPVs) and perovskites (PVKs) have the potential to disrupt the PV market due to their ease of fabrication (compatible with cheap roll-to-roll processing) and installation, as well as their significant efficiency improvements in recent years. However, rapid degradation is still an issue present in many emerging PVs, which must be addressed to enable their commercialisation. This thesis shows an OPV lifetime enhancing technique by adding the insulating polymer PMMA to the active layer, and a novel model for quantifying the impact of degradation (alongside efficiency and cost) upon levelized cost of energy (LCOE) in real world emerging PV installations. The effect of PMMA morphology on the success of a ternary strategy was investigated, leading to device design guidelines. It was found that either increasing the weight percent (wt%) or molecular weight (MW) of PMMA resulted in an increase in the volume of PMMA-rich islands, which provided the OPV protection against water and oxygen ingress. It was also found that adding PMMA can be effective in enhancing the lifetime of different active material combinations, although not to the same extent, and that processing additives can have a negative impact in the devices lifetime. A novel model was developed taking into account realistic degradation profile sourced from a literature review of state-of-the-art OPV and PVK devices. It was found that optimal strategies to improve LCOE depend on the present characteristics of a device, and that panels with a good balance of efficiency and degradation were better than panels with higher efficiency but higher degradation as well. Further, it was found that low-cost locations were more favoured from reductions in the degradation rate and module cost, whilst high-cost locations were more benefited from improvements in initial efficiency, lower discount rates and reductions in install costs

    Epilepsy Mortality: Leading Causes of Death, Co-morbidities, Cardiovascular Risk and Prevention

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    a reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected ... Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by&nbsp;..

    The potential of shade trees to improve microclimate in coffee production systems and contribute to the protection of coffee yield and quality in a changing climate

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    Climate change is a major challenge to which global coffee production must adapt. With Coffea arabica being especially sensitive to rising temperatures, shade trees present a promising adaptation strategy, as there is some evidence that they can modify microclimate. Employing an interdisciplinary approach, combining biophysical and sociological research, this study investigated the effect of shade on coffee production on the southern slope of Mt. Kilimanjaro with the aim of finding suitable strategies to optimise coffee production systems and ensure optimal yield and quality, thus assuring farmers’ livelihoods into the future, in the face of climate change. Precipitation records from coffee plantations were analysed for changes in weather patterns in the last two decades. The influence of shade on microclimate, leaf temperature, coffee yield and physical quality aspects was assessed in coffee plantations and smallholder systems. Additionally, focus group discussions and interviews with small-scale farmers were conducted to explore farmers’ knowledge on the impacts of weather extremes on coffee production and the ecosystem services different tree species provide. This research shows that climate change at Mt. Kilimanjaro manifests as droughts and shorter wet seasons with less frequent but heavier rainfall events, challenges to which coffee farmers will have to adapt. Shade trees show potential in adaptation of coffee production systems to climate change, as they reduce maximum air temperatures and can reduce leaf temperature extremes during hot periods, without having negative effects on nocturnal temperatures, which are beneficial for coffee production. In coffee plantations, no effect of shade on yields was observed while a slight reduction was observed for smallholder systems. Coffee quality benefits from shade, as different shade components are associated with an increase in bean size and weight. Farmers identified Albizia schimperiana as an important tree species, providing regulatory ecosystem services to improve coffee production. Recommendations need to take farmers’ priorities into account, including their willingness to trade some reduction in coffee production for other services, such as food, fodder or firewood, which were identified as the most important ecosystem services for farmers at Mt. Kilimanjaro

    Quantifying the Indirect Effect of Wolves on Aspen in Northern Yellowstone National Park: Evidence for a Trophic Cascade?

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    Yellowstone National Park is renowned for its incredible wildlife, and perhaps the most famous of these species is the gray wolf, which was reintroduced to the Park in the mid-1990s. After reintroduction, it was highly publicized by scientists, journalists, and environmentalists that the wolf both decreased elk density and changed elk behavior in a way that reduced elk effects on plants, a process known as a “trophic cascade.” Aspen, which is eaten by elk in winter, is one species at the forefront of Yellowstone trophic cascade research because it has been in decline across the Park for over a century. However, due to the challenges of measuring trophic cascades, there is continued uncertainty regarding the effects of wolves on aspen in northern Yellowstone. Thus, the purpose of my dissertation was to provide a comprehensive test of a trophic cascade in this system. Specifically, I used 20 years of data on aspen, elk, and wolves in Yellowstone to: 1) clarify annual trends in browsing and height of young aspen (a proxy for regeneration) after wolf reintroduction, 2) assess the influence of wolves scaring elk on aspen (“trait-mediated indirect effects”), and 3) evaluate the effect of wolves killing elk on aspen (“density-mediated indirect effects”). My research suggests that wolves indirectly contributed to increased aspen over story recruitment following their reintroduction by helping to reduce the elk population size, but elk response to the risk of wolf predation did not reduce elk foraging in a way that measurably increased aspen recruitment. Additionally, hunter harvest of elk north of the park was twice as important as wolf predation in causing increased aspen recruitment. However, despite wolves and hunters limiting elk abundance, it is still uncommon for young aspen to grow past peak browsing height (120-cm), indicating that many stands remain vulnerable to elk herbivory nearly 30 years after wolf reintroduction. These results highlight that the strength and mechanism of predator effects on plant communities are context-specific. Thus, using predator reintroduction as a tool for ecosystem restoration without considering the many factors that shape trophic cascades may result in different management and conservation outcomes than intended
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