Emergence of acquired HIV-1 drug resistance has almost been stopped in Switzerland - a 15 year prospective cohort analysis

BACKGROUND  Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS  We included 11,084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of at least one major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on patient's risk of harboring drug resistant viruses. RESULTS  The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of three-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSION  HIV-1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the pre-combination ART era. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.

DISTRIBUTION FUNCTIONS, MEAN SQUARED ERRORS, AND CONFIDENCE LIMITS FOR RIDGE REGRESSION ESTIMATORS

A large number of ridge regression estimators have been proposed and used with little knowledge of their true distributions. Because of this lack of knowledge, these estimators cannot be used to test hypotheses or to form confidence intervals.^ This paper presents a basic technique for deriving the exact distribution functions for a class of generalized ridge estimators. The technique is applied to five prominent generalized ridge estimators. Graphs of the resulting distribution functions are presented. The actual behavior of these estimators is found to be considerably different than the behavior which is generally assumed for ridge estimators.^ This paper also uses the derived distributions to examine the mean squared error properties of the estimators. A technique for developing confidence intervals based on the generalized ridge estimators is also presented. ^

Appendix A. Whole-rock major, trace and rare earth element analyses of the Ulubey volcanics, Appendix B. Analytical standards and detection limits for analyses

Collisional and post-collisional volcanic rocks in the Ulubey (Ordu) area at the western edge of the Eastern Pontide Tertiary Volcanic Province (EPTVP) in NE Turkey are divided into four suites; Middle Eocene (49.4-44.6 Ma) aged Andesite-Trachyandesite (AT), Trachyandesite-Trachydacite-Rhyolite (TTR), Trachydacite-Dacite (TD) suites, and Middle Miocene (15.1 Ma) aged Trachybasalt (TB) suite. Local stratigraphy in the Ulubey area starts with shallow marine environment sediments of the Paleocene-Eocene time and then continues extensively with sub-aerial andesitic to rhyolitic and rare basaltic volcanism during Eocene and Miocene time, respectively. Petrographically, the volcanic rocks are composed primarily of andesites/trachyandesites, with minor trachydacites/rhyolites, basalts/trachybasalts and pyroclastics, and show porphyric, hyalo-microlitic porphyric and rarely glomeroporphyric, intersertal, intergranular, fluidal and sieve textures. The Ulubey (Ordu) volcanic rocks indicate magma evolution from tholeiitic-alkaline to calc-alkaline with medium-K contents. Primitive mantle normalized trace element and chondrite normalized rare earth element (REE) patterns show that the volcanic rocks have moderate light rare earth element (LREE)/heavy rare earth element (HREE) ratios relative to E-Type MORB and depletion in Nb, Ta and Ti. High Th/Yb ratios indicate parental magma(s) derived from an enriched source formed by mixing of slab and asthenospheric melts previously modified by fluids and sediments from a subduction zone. All of the volcanic rocks share similar incompatible element ratios (e.g., La/Sm, Zr/Nb, La/Nb) and chondrite-normalized REE patterns, indicating that the basic to acidic rocks originated from the same source. The volcanic rocks were produced by the slab dehydration-induced melting of an existing metasomatized mantle source, and the fluids from the slab dehydration introduced significant large ion lithophile element (LILE) and LREE to the source, masking its inherent HFSE-enriched characteristics. The initial 87Sr/86Sr (0.7044-0.7050) and eNd (-0.3 to +3.4) ratios of the volcanics suggest that they originated from an enriched lithospheric mantle source with low Sm/Nd ratios. Integration of the geochemical, petrological and isotopical with regional and local geological data suggest that the Tertiary volcanic rocks from the Ulubey (Ordu) area were derived from an enriched mantle, which had been previously metasomatized by fluids derived from subducted slab during Eocene to Miocene in collisional and post-collisional extension-related geodynamic setting following Late Mesozoic continental collision between the Eurasian plate and the Tauride-Anatolide platform.

Reconstructed glaciation limits in Eurasia (digitized from map Fig.1)

Based on field investigations in northern Russia and interpretation of offshore seismic data, we have made a preliminary reconstruction of the maximum ice-sheet extent in the Barents and Kara Sea region during the Early/Middle Weichselian and the Late Weichselian. Our investigations indicate that the Barents and Kara ice sheets attained their maximum Weichselian positions in northern Russia prior to 50 000 yr BP, whereas the northeastern flank of the Scandinavian Ice Sheet advanced to a maximum position shortly after 17000 calendar years ago. During the Late Weichselian (25 000-10000 yr BP), much of the Russian Arctic remained ice-free. According to our reconstruction, the extent of the ice sheets in the Barents and Kara Sea region during the Late Weichselian glacial maximum was less than half that of the maximum model which, up to now, has been widely used as a boundary condition for testing and refining General Circulation Models (GCMs). Preliminary numerical-modelling experiments predict Late Weichselian ice sheets which are larger than the ice extent implied for the Kara Sea region from dated geological evidence, suggesting very low precipitation.

Pensar su tiempo, deshilvanar el orden social

Edgardo Antonio Vigo fue un artista plástico que utilizó distintas técnicas y formas de expresión, como la poesía visual, las performances urbanas, el arte correo, la escritura de manifiestos y otros textos, así como la edición de revistas, entre otras actividades. Vigo produjo su poética en clave de rebeldía de su tiempo, especialmente entre los '60 y '70, pero su rebelión transcurrió también por fuera del estereotipo más consolidado para la época. La obra de Vigo retoma algunos procedimientos de las vanguardias, como la utilización del objeto ya hecho, el uso de espacios alternativos de producción y difusión de sus obras, el abandono casi completo del formato de cuadro, entre otros. Interesa pensar en este trabajo de qué modo esta apropiación de técnicas y procedimientos previos, se combina con otra ruptura dirigida no sólo al sistema artístico, sino también al orden social. En este sentido, la obra de Vigo piensa su tiempo. ;Así como tematizó ciertos acontecimientos de relevancia política de los ámbitos nacional e internacional, también realizó una operación novedosa en su obra: la utilización del discurso judicial-administrativo. Se analizan en este trabajo algunos de sus usos en acciones artísticas. Concluimos en que se trató de una materia que incorporaría en su poética para desnaturalizarla de su lugar original, aristocrático y privatista. En este sentido, toma un aspecto no menor del funcionamiento del orden social disociándolo de su lugar normal y, al ofrecerlo a todos a través de acciones artísticas, permite una apropiación descentrada, fuera de los límites impuestos por su naturaleza

Composition of hardgrounds and of pore-water parameters in ODP Holes 166-1008 and 166-1009

Mineralogic, petrographic, and geochemical analyses of sediments recovered from two Leg 166 Ocean Drilling Program cores on the western slope of Great Bahama Bank (308 m and 437 m water depth) are used to characterize early marine diagenesis of these shallow-water, periplatform carbonates. The most pronounced diagenetic products are well-lithified intervals found almost exclusively in glacial lowstand deposits and interpreted to have formed at or near the seafloor (i.e., hardgrounds). Hardground cements are composed of high-Mg calcite (~14 mol% MgCO3), and exhibit textures typically associated with seafloor cementation. Geochemically, hardgrounds are characterized by increased d18O and Mg contents and decreased d13C, Sr, and Na contents relative to their less lithified counterparts. Despite being deposited in shallow waters that are supersaturated with the common carbonate minerals, it is clear that these sediments are also undergoing shallow subsurface diagenesis. Calculation of saturation states shows that pore waters become undersaturated with aragonite within the upper 10 m at both sites. Dissolution, and likely recrystallization, of metastable carbonates is manifested by increases in interstitial water Sr and Sr/Ca profiles with depth. We infer that the reduction in mineral saturation states and subsequent dissolution are being driven by the oxidation of organic matter in this Fe-poor carbonate system. Precipitation of burial diagenetic phases is indicated by the down-core appearance of dolomite and corresponding decrease in interstitial water Mg, and the presence of low-Mg calcite cements observed in scanning electron microscope photomicrographs.

Antagonistic interactions between the african weaver ant Oecophylla longinoda and the parasitoid Anagyrus pseudococci potentially limits suppression of the invasive mealybug Rastrococcus iceryoides

The ant Oecophylla longinoda Latreille forms a trophobiotic relationship with the invasive mealybug Rastrococus iceryoides Green and promotes the latter's infestations to unacceptable levels in the presence of their natural enemies. In this regard, the antagonistic interactions between the ant and the parasitoid Anagyrus pseudococci Girault were assessed under laboratory conditions. The percentage of parasitism of R. iceryoides by A. pseudococci was significantly higher on "ant-excluded" treatments (86.6% ± 1.27%) compared to "ant-tended" treatments (51.4% ± 4.13%). The low female-biased sex-ratio observed in the "ant-tended" treatment can be attributed to ants' interference during the oviposition phase, which disrupted parasitoids' ability to fertilize eggs. The mean foraging time, host handling time and number of successful oviposition in "ant-excluded" treatment were significantly higher compared to "ant-tended" treatments. When ant workers were allowed access to sterilized sand grains, mummified and unmummified R. iceryoides, they selectively removed the mummified mealybugs, indicating that they recognized the mummies as potential foods (1.2 ± 0.46 to 7.8 ± 1.17 mummies at 10 min intervals for 2 h). Percentage emergence from mummified R. iceryoides removed by the ants was significantly lower compared to emergence from mummies not exposed to ants. Although, host seeking parasitoids frequently evaded attacks, some were killed by the foraging ant workers (2.0 ± 0.38 to 6.0 ± 0.88 at 10 min intervals for 2 h). These results suggest for the first time that the presence of O. longinoda has a detrimental effect on the abundance, reproductive success and possibly oviposition strategy of female parasitoids, which might be a delimiting factor in field conditions if both natural enemies are to be recommended for use within the same agro-ecosystem.

Pensar su tiempo, deshilvanar el orden social

Edgardo Antonio Vigo fue un artista plástico que utilizó distintas técnicas y formas de expresión, como la poesía visual, las performances urbanas, el arte correo, la escritura de manifiestos y otros textos, así como la edición de revistas, entre otras actividades. Vigo produjo su poética en clave de rebeldía de su tiempo, especialmente entre los '60 y '70, pero su rebelión transcurrió también por fuera del estereotipo más consolidado para la época. La obra de Vigo retoma algunos procedimientos de las vanguardias, como la utilización del objeto ya hecho, el uso de espacios alternativos de producción y difusión de sus obras, el abandono casi completo del formato de cuadro, entre otros. Interesa pensar en este trabajo de qué modo esta apropiación de técnicas y procedimientos previos, se combina con otra ruptura dirigida no sólo al sistema artístico, sino también al orden social. En este sentido, la obra de Vigo piensa su tiempo. ;Así como tematizó ciertos acontecimientos de relevancia política de los ámbitos nacional e internacional, también realizó una operación novedosa en su obra: la utilización del discurso judicial-administrativo. Se analizan en este trabajo algunos de sus usos en acciones artísticas. Concluimos en que se trató de una materia que incorporaría en su poética para desnaturalizarla de su lugar original, aristocrático y privatista. En este sentido, toma un aspecto no menor del funcionamiento del orden social disociándolo de su lugar normal y, al ofrecerlo a todos a través de acciones artísticas, permite una apropiación descentrada, fuera de los límites impuestos por su naturaleza

AMS radiocarbon dates and pollen analysis from Zugspitzplatt

On the strongly karstified and almost unvegetated surface of the Zugspitzplatt, at an altitude of about 2290 m in the Wettersteingebirge, there is a doline within which over a period of several thousand years a bed of fine loess-like sediment, almost 1m thick, has accumulated. Notwithstanding the situation of this locality far above the present tree-line, this infill contains quantities of pollen and spores sufficient for pollen analysis without use of any enrichment techniques. Despite poor pollen preservation, it was possible to date the basal layers of this profile on the basis of their pollen assemblages. AMS dating (7415 ± 30 BP) has confirmed that the oldest sediments were laid down during the early Atlantic period, the time of the thermal optimum of the Holocene. At least since that time this site has never been overridden by a glacier. The moraine associated with the Löbben Oscillation between 3400 and 3100 BP - here represented by the so-called Platt Stillstand (Plattstand) - did not quite reach the doline. A diagram shows known Holocene glacial limits. The composition of the pollen assemblages from the two oldest levels with high pollen concentrations strongly suggests that the distance between the doline and the forest was much less during the Atlantic than at present.

Atterberg limits of sediments from DSDP Leg 65 Holes

Atterberg limits have been determined for 32 unconsolidated sediment samples, ranging in composition from silty clay to sandy silt and recovered from four sites drilled at the mouth of the Gulf of California during DSDP Leg 65. The liquid limit of the samples ranged from 41.5% to 157.5%, and the plastic limit from 32.8% to 65.1%. The plasticity index ranged from 5.9% to 102.0%. In some samples, the water content was less than the liquid limit. The liquidity index averaged 76% while the flow and toughness indices averaged 35% and 2.18%, respectively. On the basis of these limits, the sediments analyzed can be classified as inorganic clays of high plasticity, organic clays of moderate to high plasticity, and diatomaceous sands, silts, and silty clays of low plasticity.

Climate sensitivity across marine domains of life: limits to evolutionary adaptation shape species interactions, supplementary material

Organisms in all domains, Archaea, Bacteria, and Eukarya will respond to climate change with differential vulnerabilities resulting in shifts in species distribution, coexistence, and interactions. The identification of unifying principles of organism functioning across all domains would facilitate a cause and effect understanding of such changes and their implications for ecosystem shifts. For example, the functional specialization of all organisms in limited temperature ranges leads us to ask for unifying functional reasons. Organisms also specialize in either anoxic or various oxygen ranges, with animals and plants depending on high oxygen levels. Here, we identify thermal ranges, heat limits of growth, and critically low (hypoxic) oxygen concentrations as proxies of tolerance in a meta-analysis of data available for marine organisms, with special reference to domain-specific limits. For an explanation of the patterns and differences observed, we define and quantify a proxy for organismic complexity across species from all domains. Rising complexity causes heat (and hypoxia) tolerances to decrease from Archaea to Bacteria to uni- and then multicellular Eukarya. Within and across domains, taxon-specific tolerance limits likely reflect ultimate evolutionary limits of its species to acclimatization and adaptation. We hypothesize that rising taxon-specific complexities in structure and function constrain organisms to narrower environmental ranges. Low complexity as in Archaea and some Bacteria provide life options in extreme environments. In the warmest oceans, temperature maxima reach and will surpass the permanent limits to the existence of multicellular animals, plants and unicellular phytoplankter. Smaller, less complex unicellular Eukarya, Bacteria, and Archaea will thus benefit and predominate even more in a future, warmer, and hypoxic ocean.