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Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves’ hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) teprotumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations.

Across Europe, the genetics of the Chalcolithic/Bronze Age transition is increasingly characterized in terms of an influx of Steppe-related ancestry. The effect of this major shift on the genetic structure of populations in the Italian Peninsula remains underexplored. Here, genome-wide shotgun data for 22 individuals from commingled cave and single burials in Northeastern and Central Italy dated between 3200 and 1500 BCE provide the first genomic characterization of Bronze Age individuals (n = 8; 0.001-1.2× coverage) from the central Italian Peninsula, filling a gap in the literature between 1950 and 1500 BCE. Our study confirms a diversity of ancestry components during the Chalcolithic and the arrival of Steppe-related ancestry in the central Italian Peninsula as early as 1600 BCE, with this ancestry component increasing through time. We detect close patrilineal kinship in the burial patterns of Chalcolithic commingled cave burials and a shift away from this in the Bronze Age (2200-900 BCE) along with lowered runs of homozygosity, which may reflect larger changes in population structure. Finally, we find no evidence that the arrival of Steppe-related ancestry in Central Italy directly led to changes in frequency of 115 phenotypes present in the dataset, rather that the post-Roman Imperial period had a stronger influence, particularly on the frequency of variants associated with protection against Hansen's disease (leprosy). Our study provides a closer look at local dynamics of demography and phenotypic shifts as they occurred as part of a broader phenomenon of widespread admixture during the Chalcolithic/Bronze Age transition. ispartof: CURRENT BIOLOGY vol:31 issue:12 pages:2576-+ ispartof: location:England status: published

Abstract This paper describes some results of the research undertaken over the Brown Bank area during recent (2018/2019) geoarchaeological surveys in the North Sea which included seismic imaging, shallow (vibro)coring and dredging. It examines the benefits of simultaneous high-resolution (0.5 – 1 m) and ultra-high-resolution (10–20 cm) seismic survey techniques and a staged approach to resolving the submerged Holocene landscape in the highest possible detail for the purpose of targeted prospecting for archaeological material from the Mesolithic landscape of Doggerland. The materials recovered from such surveys offer significantly greater information due to an enhanced understanding of the context in which they were recovered. The importance of this information cannot be understated archaeologically, as few locations on land provide the opportunity to recover archaeological finds in situ within preserved landscapes. Moreover, it allows offshore areas of potential human activity to be prospected with some certainty of success.

RESUMEN. Objetivo/contexto: las democracias latinoamericanas del siglo XXI enfrentan una tensión entre “proteger” la soberanía estatal con políticas inmigratorias más restrictivas y adscribirse a los diálogos y acuerdos internacionales más liberales, que promocionan los derechos y la movilidad humana. Una mayor migración intrarregional, especialmente desde Venezuela, ha llevado a varios países a restringir derechos y libertades previamente reconocidos. Nuestro objetivo es profundizar en este giro hacia la restrictividad mediante un análisis empírico de las tendencias e intenciones legislativas de inmigración en Chile. Metodología: desde 2018, el Gobierno de Chile ha promovido medidas para “ordenar” y “regular” la inmigración. Entre estas, modificar la Ley de Migraciones de 1975. Empleamos el índice de políticas de inmigración en comparación (IMPIC), utilizando el proyecto de Ley 8970-06 y la Ley 20430 de refugiados. Conclusión: la administración chilena presenta intenciones legislativas de una mayor restrictividad frente a la inmigración económica y la reunificación familiar, que se direccionan a constreñir la movilidad humana. Originalidad: el artículo extiende el uso de IMPIC en 2010 a 2019, y lo aplica por primera vez en las intenciones legislativas de un gobierno incumbente para comprender mejor los cambios en las estrategias del país como un Estado migratorio. ABSTRACT. Objective/Context: Latin American democracies in the 21stcentury are torn between “protecting” state sovereignty by increasing restrictiveness in immigration legislation versus adhering to more liberal international agreements advocating human rights and mobility. Increases intraregional migration, especially from Venezuela, have pushed some South American countries to limit rights and freedoms previously included in immigration policies. Our objective is to further examine this shift to restrictiveness by empirically evaluating legislative intentions in Chile. Methodology: Since 2018 the Chilean government has implemented various measures aimed to achieve “orderly” and “regular” immigration, as well as proposed a law project to replace the Migration Law of 1975, adopted during the civic-military regime. We apply the Immigration Policies in Comparison (IMPIC) index using Chile’s law proposal 8970-06 and its refugee Law 20.430. Conclusion: The Chilean administration’s legislative intentions indicate tightening restrictions constraining human mobility, especially for labor immigration and family reunification. Originality: This article extends the IMPIC index from 2010 to 2019, applying it for the first time to legislative intentions of an incumbent government, to shed light on how countries, as migration states, change strategies over time. RESUMO. Objetivo/contexto: as democracias latino-americanas do século XXI enfrentam uma tensão entre ‘proteger’ a soberania estatal com mais restrições em suas políticas migratórias e subscrever aos diálogos e acordos internacionais mais liberais, promovendo os direitos e a mobilidade humana. O aumento da migração intrarregional, especialmente da Venezuela, levou vários países a restringir direitos e liberdades anteriormente reconhecidos. Nosso objetivo é o de nos aprofundar nesta inflexão restritiva, através de uma análise empírica das intenções legislativas migratórias do Chile. Metodologia: desde 2018, o governo do Chile tem promovido medidas distintas com o objetivo de “regular” e “ordenar” a imigração. Entre estes, ela modificou a Lei de Migração de 1975. Empregamos o índice de Políticas de Imigração em Comparação (IMPIC), utilizando o Projeto de Lei 8970-06 e a Lei 20.430 sobre refugiados. Conclusão: o governo chileno tem intenções legislativas para uma maior restritividade diante da imigração econômica e reunificação familiar, que têm como objetivo restringir a mobilidade humana. Originalidade: o artigo estende o uso do IMPIC em 2010 até 2019, aplicando-o pela primeira vez nas intenções legislativas de um governo em exercício para entender melhor as mudanças nas estratégias do país como um estado migratório.

Abstract In recent years the age-old question “what is the human?” has acquired a new acuteness and novel dimensions. In introducing the special issue on “Historical Thinking and the Human”, this article argues that there are two main trends behind the contemporary “crisis of human”: ecological transformations (related to human-induced climate change and planetary environmental challenges), and technological ones (including advancements in human enhancement, biotechnology and artificial intelligence). After discussing the respective anthropocenic and technoscientific redefinitions of the human, the paper theorizes three elements in an emerging new historicity of the human: first, the move from a fixed category to a dynamic and indeterminate concept, considering the human as a lifeform in movement; second, the extent to which the human is conceived of in its relational dependence on various non-human agents, organic and non-organic; and third, the reconceptualization of the human not as one but as many, to comprehend that we cannot speak of human individuality in the classical biological sense. In the final part, the article addresses the consequences of the redefinition of the human for historical thinking. It makes the case for the need to elaborate a new notion of history – captured by the phrase “more-than-human history”, and attuned to an emerging planetary regime of historicity in which historical thinking becomes able to affirm multiple temporalities: digital, technoscientific, sociocultural, human, biological and anthropocenic. The article concludes by recognizing the necessity to venture into a new transdisciplinary knowledge economy, appropriate for making sense of the contemporary constellation of the entangled human, technological and natural worlds.

Informed by postcolonial theory and more recent attempts to write alternative global histories of art and architecture, scholars have increasingly criticised the persistence of the canon and its Eu...