Quantifying rates of landscape evolution and tectonic processes by thermochronology and numerical modeling of crustal heat transport using PECUBE

PECUBE is a three-dimensional thermal-kinematic code capable of solving the heat production-diffusion-advection equation under a temporally varying surface boundary condition. It was initially developed to assess the effects of time-varying surface topography (relief) on low-temperature thermochronological datasets. Thermochronometric ages are predicted by tracking the time-temperature histories of rock-particles ending up at the surface and by combining these with various age-prediction models. In the decade since its inception, the PECUBE code has been under continuous development as its use became wider and addressed different tectonic-geomorphic problems. This paper describes several major recent improvements in the code, including its integration with an inverse-modeling package based on the Neighborhood Algorithm, the incorporation of fault-controlled kinematics, several different ways to address topographic and drainage change through time, the ability to predict subsurface (tunnel or borehole) data, prediction of detrital thermochronology data and a method to compare these with observations, and the coupling with landscape-evolution (or surface-process) models. Each new development is described together with one or several applications, so that the reader and potential user can clearly assess and make use of the capabilities of PECUBE. We end with describing some developments that are currently underway or should take place in the foreseeable future. (C) 2012 Elsevier B.V. All rights reserved.

Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

Activation of a dendritic cell-T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells.

The STEP HIV vaccine trial, which evaluated a replication-defective adenovirus type 5 (Ad5) vector vaccine, was recently stopped. The reasons for this included lack of efficacy of the vaccine and a twofold increase in the incidence of HIV acquisition among vaccinated recipients with increased Ad5-neutralizing antibody titers compared with placebo recipients. To model the events that might be occurring in vivo, the effect on dendritic cells (DCs) of Ad5 vector alone or treated with neutralizing antiserum (Ad5 immune complexes [IC]) was compared. Ad5 IC induced more notable DC maturation, as indicated by increased CD86 expression, decreased endocytosis, and production of tumor necrosis factor and type I interferons. We found that DC stimulation by Ad5 IC was mediated by the Fcgamma receptor IIa and Toll-like receptor 9 interactions. DCs treated with Ad5 IC also induced significantly higher stimulation of Ad5-specific CD8 T cells equipped with cytolytic machinery. In contrast to Ad5 vectors alone, Ad5 IC caused significantly enhanced HIV infection in DC-T cell cocultures. The present results indicate that Ad5 IC activates a DC-T cell axis that, together with the possible persistence of the Ad5 vaccine in seropositive individuals, may set up a permissive environment for HIV-1 infection, which could account for the increased acquisition of HIV-1 infection among Ad5 seropositive vaccine recipients.

Effects of anxiety on visuospatial pattern discrimination and decision-making processes: what can we learn from brain dynamics ?

Detection and discrimination of visuospatial input involve at least extracting, selecting and encoding relevant information and decision-making processes allowing selecting a response. These two operations are altered, respectively, by attentional mechanisms that change discrimination capacities, and by beliefs concerning the likelihood of uncertain events. Information processing is tuned by the attentional level that acts like a filter on perception, while decision-making processes are weighed by subjective probability of risk. In addition, it has been shown that anxiety could affect the detection of unexpected events through the modification of the level of arousal. Consequently, purpose of this study concerns whether and how decision-making and brain dynamics are affected by anxiety. To investigate these questions, the performance of women with either a high (12) or a low (12) STAI-T (State-Trait Anxiety Inventory, Spielberger, 1983) was examined in a decision-making visuospatial task where subjects have to recognize a target visual pattern from non-target patterns. The target pattern was a schematic image of furniture arranged in such a way as to give the impression of a living room. Non-target patterns were created by either the compression or the dilatation of the distances between objects. Target and non-target patterns were always presented in the same configuration. Preliminary behavioral results show no group difference in reaction time. In addition, visuo-spatial abilities were analyzed trough the signal detection theory for quantifying perceptual decisions in the presence of uncertainty (Green and Swets, 1966). This theory treats detection of a stimulus as a decision-making process determined by the nature of the stimulus and cognitive factors. Astonishingly, no difference in d' (corresponding to the distance between means of the distributions) and c (corresponds to the likelihood ratio) indexes was observed. Comparison of Event-related potentials (ERP) reveals that brain dynamics differ according to anxiety. It shows differences in component latencies, particularly a delay in anxious subjects over posterior electrode sites. However, these differences are compensated during later components by shorter latencies in anxious subjects compared to non-anxious one. These inverted effects seem indicate that the absence of difference in reaction time rely on a compensation of attentional level that tunes cortical activation in anxious subjects, but they have to hammer away to maintain performance.

Combining food web and species distribution models for improved community projections

The ability to model biodiversity patterns is of prime importance in this era of severe environmental crisis. Species assemblage along environmental gradient is subject to the interplay of biotic interactions in complement to abiotic environmental filtering. Accounting for complex biotic interactions for a wide array of species remains so far challenging. Here, we propose to use food web models that can infer the potential interaction links between species as a constraint in species distribution models. Using a plant-herbivore (butterfly) interaction dataset, we demonstrate that this combined approach is able to improve both species distribution and community forecasts. Most importantly, this combined approach is very useful in rendering models of more generalist species that have multiple potential interaction links, where gap in the literature may be recurrent. Our combined approach points a promising direction forward to model the spatial variation of entire species interaction networks. Our work has implications for studies of range shifting species and invasive species biology where it may be unknown how a given biota might interact with a potential invader or in future climate.

Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B.

BACKGROUND: Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important. METHODS: The effect of HIV-1 subtype B and non-B on the time to virological failure while taking combination antiretroviral therapy (cART) was analyzed. Other studies that have addressed this question were limited by the strong correlation between subtype and ethnicity. Our analysis was restricted to white patients from the Swiss HIV Cohort Study who started cART between 1996 and 2009. Cox regression models were performed; adjusted for age, sex, transmission category, first cART, baseline CD4 cell counts, and HIV RNA levels; and stratified for previous mono/dual nucleoside reverse-transcriptase inhibitor treatment. RESULTS: Included in our study were 4729 patients infected with subtype B and 539 with non-B subtypes. The most prevalent non-B subtypes were CRF02_AG (23.8%), A (23.4%), C (12.8%), and CRF01_AE (12.6%). The incidence of virological failure was higher in patients with subtype B (4.3 failures/100 person-years; 95% confidence interval [CI], 4.0-4.5]) compared with non-B (1.8 failures/100 person-years; 95% CI, 1.4-2.4). Cox regression models confirmed that patients infected with non-B subtypes had a lower risk of virological failure than those infected with subtype B (univariable hazard ratio [HR], 0.39 [95% CI, .30-.52; P < .001]; multivariable HR, 0.68 [95% CI, .51-.91; P = .009]). In particular, subtypes A and CRF02_AG revealed improved outcomes (multivariable HR, 0.54 [95% CI, .29-.98] and 0.39 [95% CI, .19-.79], respectively). CONCLUSIONS: Improved virological outcomes among patients infected with non-B subtypes invalidate concerns that these individuals are at a disadvantage because drugs have been designed primarily for subtype B infections.

Diagnostic accuracy of G-CSF, IL-8, and IL-1ra in critically ill children with suspected infection.

OBJECTIVE: To elucidate the diagnostic accuracy of granulocyte colony-stimulating factor (G-CSF), interleukin-8 (IL-8), and interleukin-1 receptor antagonist (IL-1ra) in identifying patients with sepsis among critically ill pediatric patients with suspected infection. DESIGN AND SETTING: Nested case-control study in a multidisciplinary neonatal and pediatric intensive care unit (PICU) PATIENTS: PICU patients during a 12-month period with suspected infection, and plasma available from the time of clinical suspicion (254 episodes, 190 patients). MEASUREMENTS AND RESULTS: Plasma levels of G-CSF, IL-8, and IL-1ra. Episodes classified on the basis of clinical and bacteriological findings into: culture-confirmed sepsis, probable sepsis, localized infection, viral infection, and no infection. Plasma levels were significantly higher in episodes of culture-confirmed sepsis than in episodes with ruled-out infection. The area under the receiver operating characteristic curve was higher for IL-8 and G-CSF than for IL-1ra. Combining IL-8 and G-CSF improved the diagnostic performance, particularly as to the detection of Gram-negative sepsis. Sensitivity was low (<50%) in detecting Staphylococcus epidermidis bacteremia or localized infections. CONCLUSIONS: In this heterogeneous population of critically ill children with suspected infection, a model combining plasma levels of IL-8 and G-CSF identified patients with sepsis. Negative results do not rule out S. epidermidis bacteremia or locally confined infectious processes. The model requires validation in an independent data-set.

Drug refractory epilepsy in brain damage: effect of dextromethorphan on EEG in four patients.

High doses of dextromethorphan (20-42 mg/kg/day) were given to four critically ill children with seizures and frequent epileptiform abnormalities in the EEG that were refractory to antiepileptic drugs. Their acute diseases (hypoxia, head trauma and hypoxia, neurodegenerative disease, hypoglycaemia) were thought to be due in part to N-methyl-D-aspartate (NMDA) receptor mediated processes. Treatment with dextromethorphan, an NMDA receptor antagonist, was started between 48 hours and 14 days after the critical incident. In three patients the EEG improved considerably within 48 hours and seizures ceased within 72 hours. In the patient with neurodegenerative disease the effect on the EEG was impressive, but the seizures were not controlled. Despite the improvement of the EEG the clinical outcome was poor in all children: three died in the critical period or due to the progressing disease; the patient with hypoglycaemia survived with severe neurological sequelae. Plasma concentrations of dextromethorphan varied between 74-1730 ng/ml and its metabolite dextrorphan varied between 349-3790 ng/ml. In one patient corresponding concentrations in CSF were lower than those in plasma. The suppression of epileptic discharges by the doses of dextromethorphan given suggests that such doses are sufficient to block NMDA receptors.

Is the diagnostic yield of upper GI endoscopy improved by the use of explicit panel-based appropriateness criteria?

BACKGROUND: Increasing the appropriateness of use of upper gastrointestinal (GI) endoscopy is important to improve quality of care while at the same time containing costs. This study explored whether detailed explicit appropriateness criteria significantly improve the diagnostic yield of upper GI endoscopy. METHODS: Consecutive patients referred for upper GI endoscopy at 6 centers (1 university hospital, 2 district hospitals, 3 gastroenterology practices) were prospectively included over a 6-month period. After controlling for disease presentation and patient characteristics, the relationship between the appropriateness of upper GI endoscopy, as assessed by explicit Swiss criteria developed by the RAND/UCLA panel method, and the presence of relevant endoscopic lesions was analyzed. RESULTS: A total of 2088 patients (60% outpatients, 57% men) were included. Analysis was restricted to the 1681 patients referred for diagnostic upper GI endoscopy. Forty-six percent of upper GI endoscopies were judged to be appropriate, 15% uncertain, and 39% inappropriate by the explicit criteria. No cancer was found in upper GI endoscopies judged to be inappropriate. Upper GI endoscopies judged appropriate or uncertain yielded significantly more relevant lesions (60%) than did those judged to be inappropriate (37%; odds ratio 2.6: 95% CI [2.2, 3.2]). In multivariate analyses, the diagnostic yield of upper GI endoscopy was significantly influenced by appropriateness, patient gender and age, treatment setting, and symptoms. CONCLUSIONS: Upper GI endoscopies performed for appropriate indications resulted in detecting significantly more clinically relevant lesions than did those performed for inappropriate indications. In addition, no upper GI endoscopy that resulted in a diagnosis of cancer was judged to be inappropriate. The use of such criteria improves patient selection for upper GI endoscopy and can thus contribute to efforts aimed at enhancing the quality and efficiency of care. (Gastrointest Endosc 2000;52:333-41).

Subduction and obduction processes in the Swiss Alps

The significance of the Brianconnais domain in the Alpine orogen is reviewed in the light of data concerning its collision with the active Adriatic margin and the passive Helvetic margin. The Brianconnais which formerly belonged to the Iberian plate, was located on the northern margin of the Alpine Tethys (Liguro-Piemont ocean) since its opening in the early-Middle Jurassic. Together with the Iberian plate the Brianconnais terrane was separated from the European plate in the Late Jurassic-Early Cretaceous, following the northern Atlantic, Bay of Biscay, Valais ocean opening. This was accompanied by the onset of subduction along the northern margin of Adria and the closure of the Alpine Tethys. Stratigraphic and metamorphic data regarding this subduction and the geohistory of the Brianconnais allows the scenario of subduction-obduction processes during the Late Cretaceous-early Tertiary in the eastern and western Alps to be specified. HP-LT metamorphism record a long-lasting history of oceanic subduction-accretion, followed in the Middle Eocene by the incorporation of the Brianconnais as an exotic terrane into the accretionary prism. Middle to Late Eocene cooling ages of the Brianconnais basement and the presence of pelagic, anorogenic sedimentation lasting until the Middle Eocene on the Brianconnais preclude any sort of collision before that time between this domain and the active Adria margin or the Helvetic margin. This is confirmed by plate reconstructions constrained by magnetic anomalies in the Atlantic domain. Only a small percentage of the former Brianconnais domain was obducted, most of the crust and lithospheric roots were subducted. This applies also to domains formerly belonging to the southern Alpine Tethys margin (Austroalpine-inner Carpathian domain). It is proposed that there was a single Palaeogene subduction zone responsible for the Alpine orogen formation (from northern Spain to the East Carpathians), with the exception of a short-lived Late Cretaceous partial closure of the Valais ocean. Subduction in the western Tethyan domain originated during the closure of the Meliata ocean during the Jurassic incorporating the Austroalpine-Carpathian domain as terranes during the Cretaceous. The subduction zone propagated into the northern margin of Adria and then to the northern margin of the Iberian plate, where it gave birth to the Pyrenean-Provencal orogenic belt. This implies the absence of a separated Cretaceous subduction zone within the Austro-Carpathian Penninic ocean. Collision of Iberia with Europe forced the subduction to jump to the SE margin of Iberia in the Eocene, creating the Apenninic orogenic wedge and inverting the vergence of subduction from south- to north-directed. (C) 1998 Elsevier Science B.V. All rights reserved.

Improved blood pressure control by monitoring compliance with antihypertensive therapy.

Compliance with antihypertensive therapy was monitored for three months using an electronic medication dispenser in 35 patients remaining hypertensive despite the once-daily administration of a blood pressure lowering drug (either as monotherapy or as fixed-dose combination therapy). During the monitoring of compliance, the treatment was unchanged but blood pressure decreased significantly (p < 0.001) from 167.9/100.4 +/- 16.3/7.2 mmHg (mean +/- SD) to 152.5/90.9 +/- 20.9/11.5 mmHg. The percentage of days with one opening per day was 80.8 +/- 20.5. Thus, discussing with the patient about compliance with the prescribed drug regimen and monitoring compliance for a few months allows better control of blood pressure. This most likely reflects increased compliance with antihypertensive drug therapy.