Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

A simple algorithm locates β-strands in the amyloid fibril core of α-synuclein, Aβ, and tau using the amino acid sequence alone

Fibrillar inclusions are a characteristic feature of the neuropathology found in the α-synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Familial forms of α-synucleinopathies have also been linked with missense mutations or gene multiplications that result in higher protein expression levels. In order to form these fibrils, the protein, α-synuclein (α-syn), must undergo a process of self-assembly in which its native state is converted from a disordered conformer into a β-sheet-dominated form. Here, we have developed a novel polypeptide property calculator to locate and quantify relative propensities for β-strand structure in the sequence of α-syn. The output of the algorithm, in the form of a simple x-y plot, was found to correlate very well with the location of the β-sheet core in α-syn fibrils. In particular, the plot features three peaks, the largest of which is completely absent for the nonfibrillogenic protein, β-syn. We also report similar significant correlations for the Alzheimer's disease-related proteins, Aβ and tau. A substantial region of α-syn is also of converting from its disordered conformation into a long amphipathic α-helical protein. We have developed the aforementioned algorithm to locate and quantify the α-helical hydrophobic moment in the amino acid sequence of α-syn. As before, the output of the algorithm, in the form of a simple x-y plot, was found to correlate very well with the location of α-helical structure in membrane bilayer-associated α-syn

Ports, routes et trafics en Occident: le cas de Narbonne

The exploration of this subject is based principally on epigraphic evidence, as illustrated in Hatzfeld’s ground-breaking work of 1919, to which may now be added the epigraphy of production and commerce, which goes hand in hand with trade and to which it owes its existence. The case studied here deals with the most westerly part of the Mediterranean, providing access to the continent through the network of routes from the areas around the Aquitaine isthmus and the Rhône isthmus as far as the Rhine and Garonne basins and out to the Atlantic Ocean. It looks at dynamic trends, phenomena which vary over time, just as contexts and economic circumstances may vary. These trends are integrated within the space formed by the routes created and used by people. The study deals with the commercial activities related to the production, transportation and consumption of goods, as well as the networks and directions of trade routes. Ports are important points of passage, places where goods are transferred, stored and distributed, as well as being the principal or secondary places of business

Warehouse Societies

International audienceWhen we are trying to imagine what the world of the warehouse was like in the last few centuries of the Republic and the first three of the Empire, we have to consider a particular type of storehouse and economic context at a time when commercial exchanges in the ports in which goods were stocked and redistributed reached their apogee. This was a time when ports were centres of constant activity in which goods were stored and redistributed and commercial exchange was at its height