CD41 T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa.

BACKGROUND Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. METHODS We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/ml in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. RESULTS After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95% confidence interval (CI): 517–541] in North America, 494/ml (95% CI: 429–559) in West Africa, 515/ml (95% CI: 508–522) in Southern Africa, 503/ml (95% CI: 478–528) in Asia and 437/ml (95% CI: 425–449) in East Africa. CONCLUSIONS CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

Bedrock bedding, landsliding and erosional budgets in the Central European Alps

We explore the controls of the litho-tectonic architecture on the erosional flux in the 370-km2 Glogn basin (European Alps). In this basin, the bedding and schistosity of the bedrock dip parallel to the topographic slope on the NW valley flank, leading to a non-dip slope situation on the opposite SE valley side. While the dip slope condition has promoted the occurrence of landslides (e.g. the c. 30-km2 deep-seated Lumnezia landslide), the opposite non-dip slope side of the valley hosts >100-m-deeply incised tributary streams. 10Be concentrations of stream sediments yield catchment-averaged denudation rates that vary between 0.27 ± 0.03 and 2.19 ± 0.37 mm a−1, while the spatially averaged denudation rate of the entire basin is 1.99 ± 0.34 mm a−1. Our 10Be-based approach reveals that the Lumnezia landslide front contributes c. 30–65% of the entire sediment budget, although it covers <5% of the Glogn basin. This suggests a primary control of the bedrock bedding on erosion rates and processes.

Glacier advances in northeastern Turkey before and during the global Last Glacial Maximum

Abstract Our study in the Başyayla Valley in northeastern Anatolia showed evidence of four glacier advances that built terminal and lateral moraines. Surface exposure dating of boulders on these moraines showed that the Maximum Ice Extent (MIE) was asynchronous with the global Last Glacial Maximum (LGM; 22.1 ± 4.3 thousand years; ka). The local {MIE} took place at least 57.0 ± 3.5 ka ago. The extent of the Başyayla Glacier during this advance is not known exactly because the boulders are only preserved on a lateral moraine. The next advance was prior to 41.5 ± 2.5 ka, and it descended down the valley to approximately 2320 m above sea level (m a.s.l.), with a glacier length of 5.3 km. During the early global LGM, the Başyayla Glacier extended for a distance of 4.9 km down to approx. 2430 m a.s.l. The last recorded advance occurred during the global LGM. This extension was 0.7 km smaller than the local {MIE} and its terminus reached 2490 m a.s.l. only. The exposure ages of boulders in a retreat position at an altitude of approx. 3045 m a.s.l. indicate that the valley has remained ice-free since the Lateglacial period. Therefore, the Lateglacial extent was limited to the cirque system in the uppermost part of the catchment. Furthermore, Holocene glacier oscillations seem to be either absent or restricted to solifluction in the whole catchment and to rock glacier movements in the southern tributary of the Başyayla Valley system.

Timing of retreat of the Reuss Glacier (Switzerland) at the end of the Last Glacial Maximum

We used cosmogenic 10Be and 36Cl to establish the timing of the onset of deglaciation after the Last Glacial Maximum of the Reuss Glacier, one of the piedmont lobes of the Alpine ice cap that reached the northern Alpine foreland in Switzerland. In this study, we sampled erratic boulders both at the frontal position in the foreland (Lenzburg and Wohlen, canton Aargau) and at the lateral Alpine border position (Seeboden moraine, Rigi, canton Schwyz). The minimum age for the beginning of retreat is 22.2 ± 1.0 ka at the frontal (terminal) position and 20.4 ± 1.0 ka at the lateral position. These ages are directly comparable with exposure ages from the other piedmont lobes in the northern Alpine foreland. Our data from the mountain called Rigi, do not support the hypothesis that boulders located external to the Seeboden moraine were deposited prior to the last glacial cycle. We present a first exposure age from an erratic boulder in a retreat position in the Alpine foreland. The Reuss Glacier was approximately 12 km behind the maximal extent no later than at 18.6 ± 0.9 ka.

The first major incision of the Swiss Deckenschotter landscape

The Swiss Deckenschotter (“cover gravels”) is the oldest Quaternary units in the northern Swiss Alpine Foreland. They are a succession of glaciofluvial gravel layers intercalated with glacial and/or overbank deposits. This lithostratigraphic sequence is called Deckenschotter because it “covers” Molasse or Mesozoic bedrock and forms mesa-type hill-tops. Deckenschotter occurs both within and beyond the extent of the Last Glacial Maximum glaciers. The Swiss Deckenschotter consist of two sub-units: Höhere (Higher) and Tiefere (Lower) Deckenschotter. Although the Höhere Deckenschotter sub-unit (HDS) is topographically higher than the Tiefere Deckenschotter, it is older. The only available age for the Swiss Deckenschotter is 2.5–1.8 Ma based on mammal remains found in HDS at the Irchel site. In this study, we present an exposure age for the topographically lowest HDS, calculated from a cosmogenic 10Be depth-profile. Our results show that the first phase of the Deckenschotter glaciations in the Swiss Alps terminated at least 1,020+80−120 ka ago, which is indicated by a significant fluvial incision. This line of evidence seems to be close to synchronous with the beginning of the Mid-Pleistocene Revolution, when the frequency of the glacial-interglacial cyclicity changed from 41 to 100 ka and the amplitude from low to high, between marine isotope stages 23 and 22.

Quaternary uplift rates of the Central Anatolian Plateau, Turkey: insights from cosmogenic isochron-burial nuclide dating of the Kızılırmak River terraces

The Central Anatolian Plateau (CAP) in Turkey is a relatively small plateau (300 × 400 km) with moderate average elevations of ∼1 km situated between the Pontide and Tauride orogenic mountain belts. Kızılırmak, which is the longest river (1355 km) within the borders of Turkey, flows within the CAP and slowly incises into lacustrine and volcaniclastic units before finally reaching the Black Sea. We dated the Cappadocia section of the Kızılırmak terraces in the CAP by using cosmogenic burial and isochron-burial dating methods with 10Be and 26Al as their absolute dating can provide insight into long-term incision rates, uplift and climatic changes. Terraces at 13, 20, 75 and 100 m above the current river indicate an average incision rate of 0.051 ± 0.01 mm/yr (51 ± 1 m/Ma) since ∼1.9 Ma. Using the base of a basalt fill above the modern course of the Kızılırmak, we also calculated 0.05–0.06 mm/yr mean incision and hence rock uplift rate for the last 2 Ma. Although this rate might be underestimated due to normal faulting along the valley sides, it perfectly matches our results obtained from the Kızılırmak terraces. Although up to 5–10 times slower, the Quaternary uplift of the CAP is closely related to the uplift of the northern and southern plateau margins respectively.

Cluster of Leptospirosis Acquired Through River Surfing in Switzerland

Background.  In Switzerland, leptospirosis is still considered as a travel-associated disease. After the surprising diagnosis of leptospirosis in a patient who was initially suspected as having primary human immunodeficiency virus infection, we recognized that acquisition of leptospirosis occurred through recreational activities and we identified additional affected individuals. Methods.  Detailed anamnesis, excluding occupational exposure, acquisition abroad, and pet contacts, enabled us to detect the source of infection and identify a cluster of leptospirosis. Convalescent sera testing was performed to confirm Leptospira infection. Microscopic agglutination tests were used to determine the infecting serovar. Results.  We identified a cluster of leptospirosis in young, previously healthy persons. Acquisition of leptospirosis was traced back to a surfing spot on a river in Switzerland (Reuss, Aargau). Clinical presentation was indistinct. Two of the 3 reported cases required hospitalization, and 1 case even suffered from meningitis. Serologic tests indicated infection with the serovar Grippotyphosa in all cases. With the exception of the case with meningitis, no antibiotics were administered, because leptospirosis was diagnosed after spontaneous resolution of most symptoms. Despite a prolonged period of convalescence in 2 cases, full recovery was achieved. Recent reports on beavers suffering from leptospirosis in this region underline the possible water-borne infection of the 3 cases and raise the question of potential wildlife reservoirs. Conclusions.  Insufficient awareness of caregivers, which may be promoted by the missing obligation to report human leptospirosis, combined with the multifaceted presentation of the disease result in significant underdiagnosis. More frequent consideration of leptospirosis as differential diagnosis is inevitable, particularly as veterinary data suggest re-emergence of the disease.

Nd, Pb, and Be isotopes of ferromanaganese crusts of the Atlantic Ocean

The isotopic composition of Nd in present-day deep waters of the central and northeastern Atlantic Ocean is thought to fingerprint mixing of North Atlantic Deep Water with Antarctic Bottom Water. The central Atlantic Romanche and Vema Fracture Zones are considered the most important pathways for deep water exchange between the western and eastern Atlantic basins today. We present new Nd isotope records of the deepwater evolution in the fracture zones obtained from ferromanganese crusts, which are inconsistent with simple water mass mixing alone prior to 3 Ma and require additional inputs from other sources. The new Pb isotope time series from the fracture zones are inexplicable by simple mixing of North Atlantic Deep Water and Antarctic Bottom Water for the entire past 33 Myr. The distinct and relatively invariable Nd and Pb isotope records of deep waters in the fracture zones appear instead to have been controlled to a large extent by contributions from Saharan dust and the Orinoco/Amazon Rivers. Thus the previously observed similarity of Nd and Pb isotope time series from the western and eastern North Atlantic basins is better explainable by direct supply of Labrador Seawater to the eastern basin via a northern pathway rather than by advection of North Atlantic Deep Water via the Romanche and Vema Fracture Zones.

Nd, Pb, and Be isotopes of ferromanaganese crusts of the South Pacific

The application of radiogenic isotopes to the study of Cenozoic circulation patterns in the South Pacific Ocean has been hampered by the fact that records from only equatorial Pacific deep water have been available. We present new Pb and Nd isotope time series for two ferromanganese crusts that grew from equatorial Pacific bottom water (D137-01, 'Nova', 7219 m water depth) and southwest Pacific deep water (63KD, 'Tasman', 1700 m water depth). The crusts were dated using 10Be/9Be ratios combined with constant Co-flux dating and yield time series for the past 38 and 23 Myr, respectively. The surface Nd and Pb isotope distributions are consistent with the present-day circulation pattern, and therefore the new records are considered suitable to reconstruct Eocene through Miocene paleoceanography for the South Pacific. The isotope time series of crusts Nova and Tasman suggest that equatorial Pacific deep water and waters from the Southern Ocean supplied the dissolved trace metals to both sites over the past 38 Myr. Changes in the isotopic composition of crust Nova are interpreted to reflect development of the Antarctic Circumpolar Current and changes in Pacific deep water circulation caused by the build up of the East Antarctic Ice Sheet. The Nd isotopic composition of the shallower water site in the southwest Pacific appears to have been more sensitive to circulation changes resulting from closure of the Indonesian seaway.