Falha de resposta à glibenclamida em criança brasileira com diabetes melito neonatal permanente e síndrome DEND devido a mutação C166Y no gene KCNJ11 (Kir6.2)

Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide.As mutações ativadoras, heterozigóticas do gene KCNJ11 (Kir6.2) são a causa mais freqüente de diabetes melito neonatal permanente (DMNP) e a terapêutica oral com sulfoniluréias tem sido bem sucedida em muitos destes casos. Relatamos o processo de substituição da insulinoterapia convencional para o tratamento oral com glibenclamida em uma paciente de 4 anos, portadora de DMNP e síndrome DEND devido a uma mutação C166Y no gene KCNJ11. A insulina NPH (0,2 U/kg/dia) foi substituída pela glibenclamida (1 mg/kg/dia e 1,5 mg/kg/dia) durante internação hospitalar. As respostas de glicose e peptídeo-C no teste de tolerância oral à glicose (OGTT), os níveis de hemoglobina glicada, o perfil de glicemias capilares de 8 pontos e a freqüência de hipoglicemias foram comparados antes e durante o tratamento com glibenclamida. Não houve melhora no controle glicêmico, nem no quadro neurológico. Concluímos que a mutação C166Y associa-se a uma forma de DMNP insensível à glibenclamida

Asking the readers: audience research into alternative journalism

Alternative forms of journalism are said to challenge the passive role of audience members as receivers and to foster active citizenship among alternative journalists and audiences. Yet the scholarly literature on alternative journalism contains more assertions about than evidence from the audience. Downing has described the audience for alternative media as “the virtually unknown”, prompting him to urge journalism scholars to undertake more audience research to help increase our understanding of this allegedly active and civic-minded public. This exploratory study of the people who regularly read a contemporary example of alternative journalism—an investigative local blog covering one UK city—is intended to contribute towards filling the gap identified by Downing. Audience views are explored by means of questionnaires and focus groups, providing some evidence that individuals are attracted to alternative journalism by their dissatisfaction with mainstream media; that they see alternative media as helping them make sense of the world; and that, to an extent, engaging with such media is both a prompt to, and a reflection of, readers’ democratic engagement as citizens. Recognising the limitations of this small study, the article concludes by reiterating Downing's call for further research

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study.

BACKGROUND: Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. METHODS: We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita.We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) - the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested - the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection. FINDINGS: Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable. INTERPRETATION: The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FUNDING: World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region.

BACKGROUND: Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine roll-out speed. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. METHODS: We fitted country-specific age-stratified compartmental transmission models to reported COVID-19 mortality in the WHO European Region to inform the immunity level before vaccine roll-out. Building upon broad recommendations from the WHO Strategic Advisory Group of Experts on Immunisation (SAGE), we examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incremental expansion to successively younger five-year age groups. We explored four roll-out scenarios based on projections or recent observations (R1-4) - the slowest scenario (R1) covers 30% of the total population by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy (cLE), comorbidity- and quality-adjusted life years (cQALY), and the value of human capital (HC). Six sets of infection-blocking and disease-reducing vaccine efficacies were considered. FINDINGS: The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics and roll-out speeds. Overall, V60 consistently performed better than or comparably to V75. There were greater benefits in prioritising older adults when roll-out is slow and when VE is low. Under faster roll-out, V+ was the most desirable option. INTERPRETATION: A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FUNDING: World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust. RESEARCH IN CONTEXT: Evidence before this study: We searched PubMed and medRxiv for articles published in English from inception to 9 Jun 2021, with the search terms: ("COVID-19" OR "SARS-CoV-2") AND ("priorit*) AND ("model*") AND ("vaccin*") and identified 66 studies on vaccine prioritization strategies. Of the 25 studies that compared two or more age-based prioritisation strategies, 12 found that targeting younger adults minimised infections while targeting older adults minimised mortality; an additional handful of studies found similar outcomes between different age-based prioritisation strategies where large outbreaks had already occurred. However, only two studies have explored age-based vaccine prioritisation using models calibrated to observed outbreaks in more than one country, and no study has explored the effectiveness of vaccine prioritisation strategies across settings with different population structures, contact patterns, and outbreak history.Added-value of this study: We evaluated various age-based vaccine prioritisation strategies for 38 countries in the WHO European Region using various health and economic outcomes for decision-making, by parameterising models using observed outbreak history, known epidemiologic and vaccine characteristics, and a range of realistic vaccine roll-out scenarios. We showed that while targeting older adults was generally advantageous, broadly targeting everyone above 60 years might perform better than or comparably to a more detailed strategy that targeted the oldest age group above 75 years followed by those in the next younger five-year age band. Rapid vaccine roll-out has only been observed in a small number of countries. If vaccine coverage can reach 80% by the end of 2021, prioritising older adults may not be optimal in terms of health and economic impact. Lower vaccine efficacy was associated with greater relative benefits only under relatively slow roll-out scenarios considered.Implication of all the available evidence: COVID-19 vaccine prioritization strategies that require more precise targeting of individuals of a specific and narrow age range may not necessarily lead to better outcomes compared to strategies that prioritise populations across broader age ranges. In the WHO European Region, prioritising all adults equally or younger adults first will only optimise health and economic impact when roll-out is rapid, which may raise between-country equity issues given the global demand for COVID-19 vaccines

Did Photosymbiont Bleaching Lead to the Demise of Planktic Foraminifer Morozovella at the Early Eocene Climatic Optimum?

The symbiont-bearing mixed-layer planktic foraminiferal genera Morozovella and Acarinina were among the most important calcifiers of early Paleogene tropical–subtropical oceans. A marked and permanent switch in the abundance of these genera is known to have occurred at low-latitude sites at the beginning of the Early Eocene Climatic Optimum(EECO), such that the relative abundance of Morozovella permanently and significantly decreased along with a progressive reduction in the number of species; concomitantly, the genus Acarinina almost doubled its abundance and diversified. Here we examine planktic foraminiferal assemblages and stable isotope compositions of their tests at Ocean Drilling Program Site 1051 (northwest Atlantic) to detail the timing of this biotic event, to document its details at the species level, and to test a potential cause: the loss of photosymbionts (bleaching). We also provide stable isotope measurements of bulk carbonate to refine the stratigraphy at Site 1051 and to determine when changes in Morozovella species composition and their test size occurred. We demonstrate that the switch in Morozovella and Acarinina abundance occurred rapidly and in coincidence with a negative carbon isotope excursion known as the J event (~53 Ma), which marks the start of the EECO.We provide evidence of photosymbiont loss after the J event from a size-restricted δ13C analysis. However, such inferred bleaching was transitory and also occurred in the acarininids. The geologically rapid switch in planktic foraminiferal genera during the early Eocene was a major evolutionary change within marine biota, but loss of photosymbionts was not the primary causal mechanism

Following the Money: The Wire and Distant American Studies

In this essay, I argue that the pedagogical, or, more generally, heuristic potential of HBO’s crime drama The Wire (2002/2008) is related to the specific institutional developments in post-network television, the show’s didactic intention, and its focus on the delineation of the economic process, or what has been called its “openly class-based” politics. I will dedicate most time to the latter, as it represents a particularly welcome intervention for American Studies, a discipline in which the problem of class has usually been either marginalized, or articulated in terms of the historically hegemonic disciplinary paradigm, that of identity

Remoção de nitrogênio amoniacal por Chlorella sp. em diferentes diluições de lixiviado de aterro sanitário/Amoniacal nitrogen removal by Chlorella sp. in different dillutions of sanitary terry dillution

Lixiviado de aterro sanitário é uma água residuária de matriz complexa de alto poder poluente. Apresenta elevadas concentrações de nitrogênio amoniacal, fósforo, matéria carbonácea e substâncias recalcitrantes. A aplicação de microalgas na remoção de poluentes do lixiviado tem sido investigada. A cepa de Chlorella sp. aplicada neste trabalho, foi isoladas do lixiviado do aterro sanitário de João Pessoa- PB. O sistema experimental constituiu-se por 3 biorreatores com volume útil de 210 mL, sendo, 200 mL de lixiviado diluído em água destilada e 10 mL de meio de cultivo de Chlorella sp. em fase estacionária, alimentados em batelada, fotoperíodo de 24 horas, temperatura de 27o C, TDH de 240 horas e concentrações afluentes de N-amoniacal de 46, 192 e 575 mg. L-1 e um controle positivo. As maiores densidades celulares foram registradas nas concentrações de N-amoniacal afluentes de 46 e 192 mg. L-1, com incrementos superiores a 250% até o 5º dia de monitoração. O menor crescimento foi obtido na concentração de nitrogênio amoniacal de 575 mg. L-1 com incrementos até o 5o dia de 12%. A análise do cálculo da massa de nitrogênio residual no sistema, indicou remoção de massa de 66, 59 e 56% para entradas afluentes de 9,66; 40,32 e 120,75 mg-N para concentrações afluentes de N- amoniacal respectivas de 46, 192 e 575 mg. L-1. Os resultados são indicativos de que a Chlorella sp. consegue adaptar-se e crescer em diferentes concentrações de nitrogênio amoniacal, possuindo potencial para ser aplicada eficientemente no tratamento terciário do lixiviado de aterro sanitário

Tratamento de lixiviado de aterro sanitário aplicando microalgas em biorreatores alimentados em batelada / Treatment of landlied from landfill applying microalges in biorreactors feeded in batch

O lixiviado de aterro sanitário é uma água residuária de difícil tratamento pois apresenta elevada carga de poluentes, dentre estes, matéria orgânica e inorgânica recalcitrantes, metais pesados e altos níveis de nitrogênio amoniacal. O estudo do tratamento de lixiviado de aterro sanitário através da aplicação de microalgas é uma biotecnologia recente e promissora visando a recuperação de recursos. Neste trabalho, investigou-se a capacidade de remoção de nitrogênio amoniacal de lixiviado in natura por microalgas isoladas do sistema de lagoas de tratamento de lixiviado do aterro sanitário de João Pessoa-PB. O sistema de tratamento foi constituído por 5 biorreatores com capacidade de 1L cada, alimentados por 750 mL de lixiviado com concentração média de 1842 mg. L-1 de N-amoniacal e 100 mL de cultivo com microalgas específicas de cada lagoa de tratamento, em temperatura de 27o C e com luminosidade de 85 µE. s-1.m-2. O regime de alimentação adotado foi em batelada com TDH de 120 horas, com amostragens em 72 e 120 horas. Foram identificados 16 táxons, dos quais, 62,5% representaram a classe Cyanophycea, dentre os quais, a clorofícea, Chlorella sp. foi dominante em todo o sistema de tratamento. Foram registrados incrementos de oxigênio dissolvido em torno de 2,6 mg. L-1 e pH entre 0,6 e 0,7. Em todos os biorreatores foi registrada eficiência superior a 50%. A maior remoção foi em torno de 86%, obtida com as microalgas isoladas da lagoa de decantação. Os resultados são indicativos de que as microalgas através de seu metabolismo, podem incorporar poluentes à biomassa