Economic centrality : how much is economics and how much is geography?

Proximity to the markets is a key determinant of the location of firms because distance still matters, as recently reported in the literature. In this paper, based on an adapted version of the most standard centrality index we propose a decomposition method which allows isolating the influence of: (i) internal and external factors; (ii) economic and geographical aspects. In order to illustrate our methodology, we consider data for 171 countries. This empirical example leads to the conclusion that the centrality level of the countries derives from different sources, requiring therefore different policy interventions in order to improve it

The Question of a Voice: With What Voice Will I Cry My Sad Fado

Fado is a traditional Portuguese music genre whose lyrics are emotionally rich, often referring to fate, love, longing, death, abandonment and helplessness. By singing these feelings a national identity is reinforced, either by the transgenerationality of the pain portrayed in these songs, or by evoking unique and untranslatable Portuguese words, such as Saudade (homesickness with melancholy) or Fado (fate in a sad and insurmountable way). In this manuscript, the universe of Fado is described and linked to a psychoanalytic meaning, through analyzing the relation between Saudade and depressiveness, what feels like to be a Fadista or the sublimation of trauma through Fado, as a song, that has been inscribed by UNESCO, on the Representative List of the Intangible Cultural Heritage of Humanity in 2011

Exposição ao Fumo Passivo no Local de Trabalho: Biomarcadores de Genotoxicidade e Susceptibilidade

Apesar dos limites impostos ao fumo em locais públicos, ainda é permitido fumar nalguns bares/restaurantes, o que constitui um potencial risco para a saúde dos indivíduos expostos. Neste trabalho pretendeu-se analisar uma potencial associação entre exposição ocupacional ao fumo de tabaco ambiental(ETS) e indução de alterações genéticas, atendendo à influência da susceptibilidade genética individual. Estudaram-se 81 empregados de bares/restaurantes, 37 expostos e 44 não expostos a ETS. Caracterizaram-se os efeitos genotóxicos recorrendo ao ensaio do micronúcleo (MN) em linfócitos e em células do epitélio oral e ao ensaio do cometa em leucócitos. Paralelamente, avaliou-se a capacidade de reparação do DNA através da quantificação de lesões induzidas pelo SEM (Ethyl methanesulfonate) no DNA de leucócitos. Analisaram-se os polimorfismos em genes de metabolização e reparação de DNA através de PCR/RFLP. Relativamente aos biomarcadores de genotoxicidade, não se observaram diferenças significativas entre o grupo exposto a ETS e o controlo. Contudo, o estímulo com EMS induziu um número significativamente menor de lesões no DNA de leucócitos dos indivíduos expostos a ETS comparativamente aos não expostos, sugerindo uma melhor capacidade de reparação do DNA - resposta adaptativa. Evidenciou-se também a influência de alguns polimorfismos em genes de metabolização na frequência de MN em células do epitélio oral e de quebras de DNA em leucócitos. Em conclusão, este estudo revelou que apesar da exposição ocupacional a ETS em bares/restaurantes não ter provocado efeitos genotóxicos detectáveis, induziu uma possível resposta adaptativa em células dos indivíduos expostos, cujo potencial impacto na saúde ainda se desconhece.Co-financiado por FCG/ ACS

FATORES QUE INFLUENCIAM A SEGURANÇA DO PACIENTE EM SERVIÇOS DE URGÊNCIA E EMERGÊNCIA: REVISÃO INTEGRATIVA

Objetivo: identificar evidências disponíveis na literatura científica acerca de fatores que interferem na segurança do paciente em serviços de urgência e emergência. Método: revisão integrativa da literatura realizada conforme as etapas: identificação do tema e questão norteadora; estabelecimento de critérios de inclusão e exclusão para os estudos; busca na literatura de estudos primários; avaliação da amostra de estudos incluídos na revisão, com extração de dados; interpretação dos resultados e apresentação. Resultados: foram selecionadas 1.449 publicações que, após aplicação dos critérios de inclusão e leitura detalhada, compuseram um conjunto de oito publicações. Nos textos foram identificados diferentes aspectos que influenciam a segurança do paciente nos serviços de urgência e emergência, os quais foram categorizados de acordo com a técnica análise de conteúdo: fatores organizacionais; falhas na comunicação da equipe e fragilidades no processo de medicação. Conclusão: múltiplos fatores interferem na segurança do paciente no ambiente emergencial, destacando-se o moderado número de pacientes e a sobrecarga de trabalho.Descritores: Segurança do Paciente. Serviço Hospitalar de Emergência. Enfermagem

Wt1 transcription factor impairs cardiomyocyte specification and drives a phenotypic switch from myocardium to epicardium.

During development, the heart grows by addition of progenitor cells to the poles of the primordial heart tube. In the zebrafish, Wilms tumor 1 transcription factor a (wt1a) and b (wt1b) genes are expressed in the pericardium, at the venous pole of the heart. From this pericardial layer, the proepicardium emerges. Proepicardial cells are subsequently transferred to the myocardial surface and form the epicardium, covering the myocardium. We found that while wt1a and wt1b expression is maintained in proepicardial cells, it is downregulated in pericardial cells that contributes cardiomyocytes to the developing heart. Sustained wt1b expression in cardiomyocytes reduced chromatin accessibility of specific genomic loci. Strikingly, a subset of wt1a- and wt1b-expressing cardiomyocytes changed their cell-adhesion properties, delaminated from the myocardium and upregulated epicardial gene expression. Thus, wt1a and wt1b act as a break for cardiomyocyte differentiation, and ectopic wt1a and wt1b expression in cardiomyocytes can lead to their transdifferentiation into epicardial-like cells.NM has been funded by SNF grant 320030E-164245 and ERC Consolidator grant 2018 819717. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Benoît Zuber is supported by SNF grant 179520 and ERA-NET NEURON grant 185536. M.O. was supported by SNF grant PCEFP3_186993.S

SATISFAÇÃO PROFISSIONAL E AMBIENTE DE TRABALHO DA EQUIPE DE ENFERMAGEM EM UNIDADES DE TERAPIA INTENSIVA

RESUMO Objetivo: verificar a associação do ambiente de trabalho e da satisfação profissional de trabalhadores de Enfermagem pelo tipo de unidade de terapia intensiva, adulto e infantil. Método: estudo transversal e analítico. Foi realizado com profissionais de Enfermagem (n=226) de unidades de terapia intensiva de três hospitais (H1, H2 e H3) gerais do Paraná, Brasil. Para mensuração da satisfação profissional, utilizou-se a versão brasileira validada do Index of Work Satisfaction e, para extrair a percepção da equipe de Enfermagem sobre o ambiente de trabalho, utilizou-se a versão brasileira validada do Nursing Work Index-Revised. Após os dados tabulados procedeu-se à análise estatística descritiva e inferencial. Resultados: de forma geral, as equipes de todos os hospitais e unidades referiam boa satisfação e percepção sobre ambiente de trabalho. As diferenças estatisticamente significativas a respeito da satisfação profissional foram as seguintes: domínio remuneração pior na UTI infantil em H2 (p-valor=0,035); e domínio interação e interação enfermeiro-médico com médias superiores (piores) na UTI adulto em H3 (p-valor=0,036 e 0,011, respectivamente). Acerca do ambiente de trabalho, houve média superior (pior ambiente) na UTI adulto em H3 para o domínio relação médico-enfermeiro (p-valor=0,023). Não houve significância estatística na comparação dos escores sobre o ambiente de trabalho para as demais instituições. Conclusão: as equipes estavam satisfeitas com o trabalho e avaliaram positivamente o seu ambiente de prática. Contudo, algumas diferenças pontuais entre as UTIs adulto e infantil podem ser consideradas para estratégias gerenciais mais assertivas, principalmente sobre aspectos relacionais na UTI adulto do hospital público

Lessons learned from the first European project on the integration of infectious diseases in testing services, data collection and country responses.

Despite the progress in effective treatments for HIV, viral hepatitis, tuberculosis and sexually transmitted infections (STIs), these infections remain major public health concerns across Europe. Recurring challenges of late presentation and unprioritized prevention programmes need to be effectively addressed in order to control and prevent transmission and ensure that people are diagnosed early and rapidly enter the care system. The prevalence of co-infections is high due to the social context of key populations and the shared modes of transmission, varying with local epidemiology, which underlines the need to combine efforts throughout the continuum of care

The diversity and evolution of pollination systems in large plant clades: Apocynaceae as a case study

Background and Aims Large clades of angiosperms are often characterized by diverse interactions with pollinators, but how these pollination systems are structured phylogenetically and biogeographically is still uncertain for most families. Apocynaceae is a clade of >5300 species with a worldwide distribution. A database representing >10 % of species in the family was used to explore the diversity of pollinators and evolutionary shifts in pollination systems across major clades and regions. Methods The database was compiled from published and unpublished reports. Plants were categorized into broad pollination systems and then subdivided to include bimodal systems. These were mapped against the five major divisions of the family, and against the smaller clades. Finally, pollination systems were mapped onto a phylogenetic reconstruction that included those species for which sequence data are available, and transition rates between pollination systems were calculated. Key Results Most Apocynaceae are insect pollinated with few records of bird pollination. Almost three-quarters of species are pollinated by a single higher taxon (e.g. flies or moths); 7 % have bimodal pollination systems, whilst the remaining approx. 20 % are insect generalists. The less phenotypically specialized flowers of the Rauvolfioids are pollinated by a more restricted set of pollinators than are more complex flowers within the Apocynoids + Periplocoideae + Secamonoideae + Asclepiadoideae (APSA) clade. Certain combinations of bimodal pollination systems are more common than others. Some pollination systems are missing from particular regions, whilst others are over-represented. Conclusions Within Apocynaceae, interactions with pollinators are highly structured both phylogenetically and biogeographically. Variation in transition rates between pollination systems suggest constraints on their evolution, whereas regional differences point to environmental effects such as filtering of certain pollinators from habitats. This is the most extensive analysis of its type so far attempted and gives important insights into the diversity and evolution of pollination systems in large clades

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years