Non-Hodgkin lymphoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

OBJECTIVE: To assess the long-term effect of HAART on non-Hodgkin lymphoma (NHL) incidence in people with HIV (PHIV). DESIGN: Follow-up of the Swiss HIV Cohort Study (SHCS). METHODS: Between 1984 and 2006, 12 959 PHIV contributed a total of 75 222 person-years (py), of which 36 787 were spent under HAART. Among these PHIV, 429 NHL cases were identified from the SHCS dataset and/or by record linkage with Swiss Cantonal Cancer Registries. Age- and gender-standardized incidence was calculated and Cox regression was used to estimate hazard ratios (HR). RESULTS: NHL incidence reached 13.6 per 1000 py in 1993-1995 and declined to 1.8 in 2002-2006. HAART use was associated with a decline in NHL incidence [HR = 0.26; 95% confidence interval (CI), 0.20-0.33], and this decline was greater for primary brain lymphomas than other NHL. Among non-HAART users, being a man having sex with men, being 35 years of age or older, or, most notably, having low CD4 cell counts at study enrollment (HR = 12.26 for < 50 versus >or= 350 cells/microl; 95% CI, 8.31-18.07) were significant predictors of NHL onset. Among HAART users, only age was significantly associated with NHL risk. The HR for NHL declined steeply in the first months after HAART initiation (HR = 0.46; 95% CI, 0.27-0.77) and was 0.12 (95% CI, 0.05-0.25) 7 to10 years afterwards. CONCLUSIONS: HAART greatly reduced the incidence of NHL in PHIV, and the influence of CD4 cell count on NHL risk. The beneficial effect remained strong up to 10 years after HAART initiation.

Biogeochemical variability during the past 3.6 million years recorded by FTIR spectroscopy in the sediment record of Lake El'gygytgyn, Far East Russian Arctic

Abstract. A number of studies have shown that Fourier transform infrared spectroscopy (FTIRS) can be applied to quantitatively assess lacustrine sediment constituents. In this study, we developed calibration models based on FTIRS for the quantitative determination of biogenic silica (BSi; n = 420; gradient: 0.9–56.5 %), total organic carbon (TOC; n = 309; gradient: 0–2.9 %), and total inorganic carbon (TIC; n = 152; gradient: 0–0.4 %) in a 318 m-long sediment record with a basal age of 3.6 million years from Lake El’gygytgyn, Far East Russian Arctic. The developed partial least squares (PLS) regression models yield high cross-validated (CV) R2 CV = 0.86–0.91 and low root mean square error of crossvalidation (RMSECV) (3.1–7.0% of the gradient for the different properties). By applying these models to 6771 samples from the entire sediment record, we obtained detailed insight into bioproductivity variations in Lake El’gygytgyn throughout the middle to late Pliocene and Quaternary. High accumulation rates of BSi indicate a productivity maximum during the middle Pliocene (3.6–3.3 Ma), followed by gradually decreasing rates during the late Pliocene and Quaternary. The average BSi accumulation during the middle Pliocene was �3 times higher than maximum accumulation rates during the past 1.5 million years. The indicated progressive deterioration of environmental and climatic conditions in the Siberian Arctic starting at ca. 3.3 Ma is consistent with the first occurrence of glacial periods and the finally complete establishment of glacial–interglacial cycles during the Quaternary.

A 350 ka record of climate change from Lake El'gygytgyn, Far East Russian Arctic: refining the pattern of climate modes by means of cluster analysis

Abstract. Rock magnetic, biochemical and inorganic records of the sediment cores PG1351 and Lz1024 from Lake El’gygytgyn, Chukotka peninsula, Far East Russian Arctic, were subject to a hierarchical agglomerative cluster analysis in order to refine and extend the pattern of climate modes as defined by Melles et al. (2007). Cluster analysis of the data obtained from both cores yielded similar results, differentiating clearly between the four climate modes warm, peak warm, cold and dry, and cold and moist. In addition, two transitional phases were identified, representing the early stages of a cold phase and slightly colder conditions during a warm phase. The statistical approach can thus be used to resolve gradual changes in the sedimentary units as an indicator of available oxygen in the hypolimnion in greater detail. Based upon cluster analyses on core Lz1024, the published succession of climate modes in core PG1351, covering the last 250 ka, was modified and extended back to 350 ka. Comparison to the marine oxygen isotope (�18O) stack LR04 (Lisiecki and Raymo, 2005) and the summer insolation at 67.5� N, with the extended Lake El’gygytgyn parameter records of magnetic susceptibility (�LF), total organic carbon content (TOC) and the chemical index of alteration (CIA; Minyuk et al., 2007), revealed that all stages back to marine isotope stage (MIS) 10 and most of the substages are clearly reflected in the pattern derived from the cluster analysis.

High-resolution glacial and deglacial record of atmospheric methane by continuous-flow and laser spectrometer analysis along the NEEM ice core

The Greenland NEEM (North Greenland Eemian Ice Drilling) operation in 2010 provided the first opportunity to combine trace-gas measurements by laser spectroscopic instruments and continuous-flow analysis along a freshly drilled ice core in a field-based setting. We present the resulting atmospheric methane (CH4) record covering the time period from 107.7 to 9.5 ka b2k (thousand years before 2000 AD). Companion discrete CH4 measurements are required to transfer the laser spectroscopic data from a relative to an absolute scale. However, even on a relative scale, the high-resolution CH4 data set significantly improves our knowledge of past atmospheric methane concentration changes. New significant sub-millennial-scale features appear during interstadials and stadials, generally associated with similar changes in water isotopic ratios of the ice, a proxy for local temperature. In addition to the midpoint of Dansgaard–Oeschger (D/O) CH4 transitions usually used for cross-dating, sharp definition of the start and end of these events brings precise depth markers (with ±20 cm uncertainty) for further cross-dating with other palaeo- or ice core records, e.g. speleothems. The method also provides an estimate of CH4 rates of change. The onsets of D/O events in the methane signal show a more rapid rate of change than their endings. The rate of CH4 increase associated with the onsets of D/O events progressively declines from 1.7 to 0.6 ppbv yr−1 in the course of marine isotope stage 3. The largest observed rate of increase takes place at the onset of D/O event #21 and reaches 2.5 ppbv yr−1.

Microneurography in rats: a minimally invasive method to record single C-fiber action potentials from peripheral nerves in vivo

Microneurography is a method suitable for recording intraneural single or multiunit action potentials in conscious subjects. Microneurography has rarely been applied to animal experiments, where more invasive methods, like the teased fiber recording technique, are widely used. We have tested the feasibility of microneurographic recordings from the peripheral nerves of rats. Tungsten microelectrodes were inserted into the sciatic nerve at mid-thigh level. Single or multiunit action potentials evoked by regular electrical stimulation were recorded, digitized and displayed as a raster plot of latencies. The method allows unambiguous recording and recognition of single C-fiber action potentials from an in vivo preparation, with minimal disruption of the nerve being recorded. Multiple C-fibers can be recorded simultaneously for several hours, and if the animal is allowed to recover, repeated recording sessions can be obtained from the same nerve at the same level over a period of weeks or months. Also, single C units can be functionally identified by their changes in latency to natural stimuli, and insensitive units can be recognized as 'silent' nociceptors or sympathetic efferents by their distinctive profiles of activity-dependent slowing during repetitive electrical stimulation, or by the effect on spontaneous efferent activity of a proximal anesthetic block. Moreover, information about the biophysical properties of C axons can be obtained from their latency recovery cycles. Finally, we show that this preparation is potentially suitable for the study of C-fiber behavior in models of neuropathies and nerve lesions, both under resting conditions and in response to drug administration.

Glacier mass balance reconstruction by sublimation induced enrichment of chemical species on Cerro Tapado (Chilean Andes)

A 36 m long ice core down to bedrock from the Cerro Tapado glacier (5536 m a.s.l, 30°08' S, 69°55' W) was analyzed to reconstruct past climatic conditions for Northern Chile. Because of the marked seasonality in the precipitation (short wet winter and extended dry summer periods) in this region, major snow ablation and related post-depositional processes occur on the glacier surface during summer periods. They include predominantly sublimation and dry deposition. Assuming that, like measured during the field campaign, the enrichment of chloride was always related to sublimation, the chemical record along the ice core may be applied to reconstruct the history of such secondary processes linked to the past climatic conditions over northern Chile. For the time period 1962–1999, a mean annual net accumulation of 316 mm water equivalent (weq) and 327 mm weq loss by sublimation was deduced by this method. This corresponds to an initial total annual accumulation of 539 mm weq. The annual variability of the accumulation and sublimation is related with the Southern Oscillation Index (SOI): higher net-accumulation during El-Niño years and more sublimation during La Niña years. The deepest part of the ice record shows a time discontinuity; with an ice body deposited under different climatic conditions: 290 mm higher precipitation but with reduced seasonal distribution (+470 mm in winter and –180 mm in summer) and –3°C lower mean annual temperature. Unfortunately, its age is unknown. The comparison with regional proxy data however let us conclude that the glacier buildup did most likely occur after the dry mid-Holocene.

Radiocarbon analysis in an Alpine ice core: Record of anthropogenic and biogenic contributions to carbonaceous Radiocarbon analysis in an Alpine ice core: Record of anthropogenic and biogenic contributions to carbonaceous aerosols in the past (1650-1940)

Long-term concentration records of carbonaceous particles (CP) are of increasing interest in climate research due to their not yet completely understood effects on climate. Nevertheless, only poor data on their concentrations and sources before the 20th century are available. We present a first long-term record of organic carbon (OC) and elemental carbon (EC) concentrations – the two main fractions of CP – along with the corresponding fraction of modern carbon (fM) derived from radiocarbon (14C) analysis in ice. This allows a distinction and quantification of natural (biogenic) and anthropogenic (fossil) sources in the past. CP were extracted from an ice archive, with resulting carbon quantities in the microgram range. Analysis of 14C by accelerator mass spectrometry (AMS) was therefore highly demanding. We analysed 33 samples of 0.4 to 1 kg ice from a 150.5 m long ice core retrieved at Fiescherhorn glacier in December 2002 (46°33'3.2" N, 08°04'0.4" E; 3900 m a.s.l.). Samples were taken from bedrock up to the firn/ice transition, covering the time period 1650–1940 and thus the transition from the pre-industrial to the industrial era. Before ~1850, OC was approaching a purely biogenic origin with a mean concentration of 24 μg kg−1 and a standard deviation of 7 μg kg−1. In 1940, OC concentration was about a factor of 3 higher than this biogenic background, almost half of it originating from anthropogenic sources, i.e. from combustion of fossil fuels. The biogenic EC concentration was nearly constant over the examined time period with 6 μg kg−1 and a standard deviation of 1 μg kg−1. In 1940, the additional anthropogenic input of atmospheric EC was about 50 μg kg−1.

Heart failure in two West Highland white terriers caused by congenital angiomatous cardiac anomaly

The paper describes the clinical and pathological characteristics of an unusual cystic congenital cardiac anomaly that caused clinical signs of congestive heart failure, respiratory distress and cardiac arrhythmias in two West Highland white terrier puppies. In both dogs a definitive diagnosis was made postmortem.

Synchronisation of the EDML and EDC ice cores for the last 52 kyr by volcanic signature matching

A common time scale for the EPICA ice cores from Dome C (EDC) and Dronning Maud Land (EDML) has been established. Since the EDML core was not drilled on a dome, the development of the EDML1 time scale for the EPICA ice core drilled in Dronning Maud Land was based on the creation of a detailed stratigraphic link between EDML and EDC, which was dated by a simpler 1D ice-flow model. The synchronisation between the two EPICA ice cores was done through the identification of several common volcanic signatures. This paper describes the rigorous method, using the signature of volcanic sulfate, which was employed for the last 52 kyr of the record. We estimated the discrepancies between the modelled EDC and EDML glaciological age scales during the studied period, by evaluating the ratio R of the apparent duration of temporal intervals between pairs of isochrones. On average R ranges between 0.8 and 1.2 corresponding to an uncertainty of up to 20% in the estimate of the time duration in at least one of the two ice cores. Significant deviations of R up to 1.4–1.5 are observed between 18 and 28 kyr before present (BP), where present is defined as 1950. At this stage our approach does not allow us unequivocally to find out which of the models is affected by errors, but assuming that the thinning function at both sites and accumulation history at Dome C (which was drilled on a dome) are correct, this anomaly can be ascribed to a complex spatial accumulation variability (which may be different in the past compared to the present day) upstream of the EDML core.

Electronic medical record systems, data quality and loss to follow-up: survey of antiretroviral therapy programmes in resource-limited settings

OBJECTIVE: To describe the electronic medical databases used in antiretroviral therapy (ART) programmes in lower-income countries and assess the measures such programmes employ to maintain and improve data quality and reduce the loss of patients to follow-up. METHODS: In 15 countries of Africa, South America and Asia, a survey was conducted from December 2006 to February 2007 on the use of electronic medical record systems in ART programmes. Patients enrolled in the sites at the time of the survey but not seen during the previous 12 months were considered lost to follow-up. The quality of the data was assessed by computing the percentage of missing key variables (age, sex, clinical stage of HIV infection, CD4+ lymphocyte count and year of ART initiation). Associations between site characteristics (such as number of staff members dedicated to data management), measures to reduce loss to follow-up (such as the presence of staff dedicated to tracing patients) and data quality and loss to follow-up were analysed using multivariate logit models. FINDINGS: Twenty-one sites that together provided ART to 50 060 patients were included (median number of patients per site: 1000; interquartile range, IQR: 72-19 320). Eighteen sites (86%) used an electronic database for medical record-keeping; 15 (83%) such sites relied on software intended for personal or small business use. The median percentage of missing data for key variables per site was 10.9% (IQR: 2.0-18.9%) and declined with training in data management (odds ratio, OR: 0.58; 95% confidence interval, CI: 0.37-0.90) and weekly hours spent by a clerk on the database per 100 patients on ART (OR: 0.95; 95% CI: 0.90-0.99). About 10 weekly hours per 100 patients on ART were required to reduce missing data for key variables to below 10%. The median percentage of patients lost to follow-up 1 year after starting ART was 8.5% (IQR: 4.2-19.7%). Strategies to reduce loss to follow-up included outreach teams, community-based organizations and checking death registry data. Implementation of all three strategies substantially reduced losses to follow-up (OR: 0.17; 95% CI: 0.15-0.20). CONCLUSION: The quality of the data collected and the retention of patients in ART treatment programmes are unsatisfactory for many sites involved in the scale-up of ART in resource-limited settings, mainly because of insufficient staff trained to manage data and trace patients lost to follow-up.

A 700-year paleoecological record of boreal ecosystem responses to climatic variation from Alaska

Recent observations and model simulations have highlighted the sensitivity of the forest - tundra ecotone to climatic forcing. In contrast, paleoecological studies have not provided evidence of tree-line fluctuations in response to Holocene climatic changes in Alaska, suggesting that the forest - tundra boundary in certain areas may be relatively stable at multicentennial to millennial time scales. We conducted a multiproxy study of sediment cores from an Alaskan lake near the altitudinal limits of key boreal-forest species. Paleoecological data were compared with independent climatic reconstructions to assess ecosystem responses of the forest - tundra boundary to Little Ice Age (LIA) climatic. uctuations. Pollen, diatom, charcoal, macrofossil, and magnetic analyses provide the first continuous record of vegetation -. re - climate interactions at decadal to centennial time scales during the past 700 years from southern Alaska. Boreal-forest diebacks characterized by declines of Picea mariana, P. glauca, and tree Betula occurred during the LIA ( AD 1500 - 1800), whereas shrubs ( Alnus viridis, Betula glandulosa/nana) and herbaceous taxa (Epilobium, Aconitum) expanded. Marked increases in charcoal abundance and changes in magnetic properties suggest increases in. re importance and soil erosion during the same period. In addition, the conspicuous reduction or disappearance of certain aquatic ( e. g., Isoetes, Nuphar, Pediastrum) and wetland ( Sphagnum) plants and major shifts in diatom assemblages suggest pronounced lake-level. uctuations and rapid ecosystem reorganization in response to LIA climatic deterioration. Our results imply that temperature shifts of 1 - 2 degrees C, when accompanied by major changes in moisture balance, can greatly alter high-altitudinal terrestrial, wetland, and aquatic ecosystems, including conversion between boreal-forest tree line and tundra. The climatic and ecosystem variations in our study area appear to be coherent with changes in solar irradiance, suggesting that changes in solar activity contributed to the environmental instability of the past 700 years.

[Neuromonitoring and neuroprotection in cardiac anaesthesia. Nationwide survey conducted by the Cardiac Anaesthesia Working Group of the German Society of Anaesthesiology and Intensive Care Medicine]

OBJECTIVE: The primary objective of this nationwide survey carried out in department of cardiac anesthesia in Germany was to identify current practice with regard to neuromonitoring und neuroprotection. METHODOLOGY: The data are based on a questionnaire sent out to all departments of cardiac anesthesia in Germany between October 2007 und January 2008. The anonymized questionnaire contained 26 questions about the practice of preoperative evaluation of cerebral vessels, intra-operative use of neuromonitoring, the nature und application of cerebral protective measures, perfusion management during cardiopulmonary bypass, postoperative evaluation of neurological status, and training in the field of cerebral monitoring. RESULTS: Of the 80 mailed questionnaires 55% were returned and 90% of department evaluated cerebral vessels preoperatively with duplex ultrasound. The methods used for intra-operative neuromonitoring are electroencephalography (EEG, 60%) for type A dissections (38.1%), for elective surgery on the thoracic and thoraco-abdominal aorta (34.1% and 31.6%, respectively) and in carotid surgery (43.2%) near infrared spectroscopy (40%), evoked potentials (30%) and transcranial Doppler sonography (17.5%), with some centers using combined methods. In most departments the central nervous system is not subjected to monitoring during bypass surgery, heart valve surgery, or minimally invasive surgery. Cerebral protective measures used comprise patient cooling on cardio-pulmonary bypass (CPB 100%), extracorporeal cooling of the head (65%) and the administration of corticosteroids (58%), barbiturates (50%) and antiepileptic drugs (10%). Neuroprotective anesthesia consists of administering inhalation anesthetics (32.5%; sevoflurane 76.5%) and intravenous anesthesia (20%; propofol and barbiturates each accounting for 46.2%). Of the departments 72.5% cool patients as a standard procedure for surgery involving cardiovascular arrest and 37.5% during all surgery using CPB. In 84.6% of department CPB flow equals calculated cardiac output (CO) under normothermia, while the desired mean arterial pressure (MAP) varies between 60 and 70 mmHg (43.9%) and between 50 and 60 mmHg (41.5%), respectively. At body temperatures less than 18 degrees C CPB flow is reduced below the calculated CO (70%) while 27% of departments use normothermic flow rates. The preferred MAP under hypothermia is between 50 and 60 mmHg (59%). The results of intra-operative neuromonitoring are documented on the anesthesia record (77%). In 42.5% of the departments postoperative neurological function is estimated by the anesthesiologist. Continuing education sessions pertaining to neuromonitoring are organized on a regular basis in 32.5% of the departments and in 37.5% individual physicians are responsible for their own neuromonitoring education. CONCLUSION: The present survey data indicate that neuromonitoring and neuroprotective therapy during CPB is not standardized in cardiac anesthesiology departments in Germany. The systemic use of available methods to implement multimodal neuromonitoring would be desirable.