Pharmacological management of narcolepsy in children and adolescents

Paroxysmal Cerebral Disorder

Pharmacological management of narcolepsy in children and adolescents

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Environmental change in the Limfjord, Denmark (ca 7500–1500 cal yrs BP): a multiproxy study

The Limfjord region of northern Jutland, Denmark, supports a rich archaeological record dating back to the Mesolithic, which documents long-term change in human practices and utilisation of marine resources since approximately 7500 BP. The presence and availability of marine resources in the Limfjord is sensitively regulated by environmental parameters such as salinity, sedimentary regime, nutrient status and primary productivity, but long-term changes in these parameters are currently poorly understood. In this study a multiproxy approach (including sedimentary parameters, diatoms, molluscs, foraminifera, sedimentary pigments, C and O stable isotopes and plant macrofossils) has been adopted to assess environmental change over the period ca 7500–1500 cal yrs BP at Kilen, a coastal fjord (before AD 1856) situated in the Western Limfjord. A diatom-based salinity transfer function based on a pan-Baltic training set has been applied to the fossil diatom dataset for quantitative assessment of salinity change over the study period. This study demonstrates that large-scale shifts in salinity are a common feature of the Limfjord's long-term history and are driven by the level of connection with the North Sea and the Skagerrak respectively, which in turn is likely driven by the complex interplay between climate, sea-level change, current velocity and rates of erosion/sedimentary accretion. Three shifts in state at Kilen are identified over the study period: a deep, periodically stratified fjord with medium–high salinity (and high productivity) between ca 7500–5000 BP, followed by a gradual transition to a shallow benthic system with more oceanic conditions (i.e. higher salinity, lower productivity, slower sedimentary accumulation rate and poorer fossil preservation) after ca 5000 BP and no stratification after ca 4400 BP, and lastly, within this shallow phase, an abrupt shift to brackish conditions around 2000 BP. Environmental–societal interactions are discussed on the basis of the data presented in this study and current environmental hypotheses for cultural change are challenge

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®