High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease

Background Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIATM HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. Methods Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. Results HIV-1 RNA <50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. Conclusions The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.

Increased phase synchronization during continuous face integration measured simultaneously with EEG and fMRI

Gamma zero-lag phase synchronization has been measured in the animal brain during visual binding. Human scalp EEG studies used a phase locking factor (trial-to-trial phase-shift consistency) or gamma amplitude to measure binding but did not analyze common-phase signals so far. This study introduces a method to identify networks oscillating with near zero-lag phase synchronization in human subjects.

Is gamma band EEG synchronization reduced during auditory driving in schizophrenia patients with auditory verbal hallucinations?

Auditory verbal hallucinations (AVH) in schizophrenia patients assumingly result from a state inadequate activation of the primary auditory system. We tested brain responsiveness to auditory stimulation in healthy controls (n=26), and in schizophrenia patients that frequently (n=18) or never (n=11) experienced AVH. Responsiveness was assessed by driving the EEG with click-tones at 20, 30 and 40Hz. We compared stimulus induced EEG changes between groups using spectral amplitude maps and a global measure of phase-locking (GFS). As expected, the 40Hz stimulation elicited the strongest changes. However, while controls and non-hallucinators increased 40Hz EEG activity during stimulation, a left-lateralized decrease was observed in the hallucinators. These differences were significant (p=.02). As expected, GFS increased during stimulation in controls (p=.08) and non-hallucinating patients (p=.06), which was significant when combining the two groups (p=.01). In contrast, GFS decreased with stimulation in hallucinating patients (p=0.13), resulting in a significantly different GFS response when comparing subjects with and without AVH (p<.01). Our data suggests that normally, 40Hz stimulation leads to the activation of a synchronized network representing the sensory input, but in hallucinating patients, the same stimulation partly disrupts ongoing activity in this network.

Developmental changes of BOLD signal correlations with global human EEG power and synchronization during working memory

In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that these opposite correlations with different distributions undergo similar and significant neuronal developments with brain maturation.

Diagnostic performance of line-immunoassay based algorithms for incident HIV-1 infection

Background Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have previously demonstrated that a patient's antibody reaction pattern in a confirmatory line immunoassay (INNO-LIA™ HIV I/II Score) provides information on the duration of infection, which is unaffected by clinical, immunological and viral variables. In this report we have set out to determine the diagnostic performance of Inno-Lia algorithms for identifying incident infections in patients with known duration of infection and evaluated the algorithms in annual cohorts of HIV notifications. Methods Diagnostic sensitivity was determined in 527 treatment-naive patients infected for up to 12 months. Specificity was determined in 740 patients infected for longer than 12 months. Plasma was tested by Inno-Lia and classified as either incident (< = 12 m) or older infection by 26 different algorithms. Incident infection rates (IIR) were calculated based on diagnostic sensitivity and specificity of each algorithm and the rule that the total of incident results is the sum of true-incident and false-incident results, which can be calculated by means of the pre-determined sensitivity and specificity. Results The 10 best algorithms had a mean raw sensitivity of 59.4% and a mean specificity of 95.1%. Adjustment for overrepresentation of patients in the first quarter year of infection further reduced the sensitivity. In the preferred model, the mean adjusted sensitivity was 37.4%. Application of the 10 best algorithms to four annual cohorts of HIV-1 notifications totalling 2'595 patients yielded a mean IIR of 0.35 in 2005/6 (baseline) and of 0.45, 0.42 and 0.35 in 2008, 2009 and 2010, respectively. The increase between baseline and 2008 and the ensuing decreases were highly significant. Other adjustment models yielded different absolute IIR, although the relative changes between the cohorts were identical for all models. Conclusions The method can be used for comparing IIR in annual cohorts of HIV notifications. The use of several different algorithms in combination, each with its own sensitivity and specificity to detect incident infection, is advisable as this reduces the impact of individual imperfections stemming primarily from relatively low sensitivities and sampling bias.

Decreased EEG synchronization in Alzheimer's disease and mild cognitive impairment

The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.

Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies, we set out to test whether TBS is associated with changes of neuronal synchronization as assessed by surface EEG. In four healthy subjects one TBS train of 600 pulses (200 bursts, each burst consisting of 3 pulses at 30 Hz, repeated at intervals of 100 ms) was applied over the right frontal eye field and EEG synchronization was assessed in a time-resolved manner over 60 min by using a non-overlapping moving window. For each time step the linear cross-correlation matrix for six EEG channels of the right and for the six homotopic EEG channels of the left hemisphere were computed and their largest eigenvalues used to assess changes of synchronization. Synchronization was computed for broadband EEG and for the delta, theta, alpha, beta and gamma frequency bands. In all subjects EEG synchronization of the stimulated hemisphere was significantly and persistently increased relative to EEG synchronization of the unstimulated hemisphere. This effect occurred immediately after TBS for the theta, alpha, beta and gamma frequency bands and 10-20 min after TBS for broadband and delta frequency band EEG. Our results demonstrate that TBS is associated with increased neuronal synchronization of the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere. We speculate that enhanced synchronization interferes with cortical information processing and thus may be a neurophysiological correlate of the impaired behavioural performance detected previously.

Algorithms for autonomous tandem operation of a dual M113 system

In mid-July 2003, the U.S. Army Tank-Automotive & Armaments Command (TACOM) performed a series of experiments at Keweenaw Research Center (KRC), with a remote operated mine roller system. This system, named Panther Lite, consists of two M113 Armored Personnel Carriers (APC’s) connected by a Tandem Vehicle Linkage Assembly (TVLA). The system has three sets of mine rollers, two of which are connected to the front of the lead vehicle with one set trailing from the trail vehicle. Currently, the system requires two joystick controllers. One regulates the braking of the tracks, throttle, and transmission of the lead vehicle and the other controls the braking and throttle of the rear vehicle. One operator controls both joysticks, attempting to maneuver the lead vehicle along a desired path. At the same time, this operator makes compensation maneuvers to reduce lateral loads in the TVLA and to guide the rear mine rollers along the desired path. The purpose of this project is to create algorithms that would allow the slave (trail) vehicle to operate using inputs that maneuver the control (lead) vehicle. The project will be completed by first reconstructing the experimental data. Kinematic models will be generated and simulations created. The models will then be correlated with the reconstructions of the experimental data. The successful completion of this project will be a first step to eliminating the need for the second joystick.

Control algorithms for large scale adaptive optics

In this dissertation, the problem of creating effective large scale Adaptive Optics (AO) systems control algorithms for the new generation of giant optical telescopes is addressed. The effectiveness of AO control algorithms is evaluated in several respects, such as computational complexity, compensation error rejection and robustness, i.e. reasonable insensitivity to the system imperfections. The results of this research are summarized as follows: 1. Robustness study of Sparse Minimum Variance Pseudo Open Loop Controller (POLC) for multi-conjugate adaptive optics (MCAO). The AO system model that accounts for various system errors has been developed and applied to check the stability and performance of the POLC algorithm, which is one of the most promising approaches for the future AO systems control. It has been shown through numerous simulations that, despite the initial assumption that the exact system knowledge is necessary for the POLC algorithm to work, it is highly robust against various system errors. 2. Predictive Kalman Filter (KF) and Minimum Variance (MV) control algorithms for MCAO. The limiting performance of the non-dynamic Minimum Variance and dynamic KF-based phase estimation algorithms for MCAO has been evaluated by doing Monte-Carlo simulations. The validity of simple near-Markov autoregressive phase dynamics model has been tested and its adequate ability to predict the turbulence phase has been demonstrated both for single- and multiconjugate AO. It has also been shown that there is no performance improvement gained from the use of the more complicated KF approach in comparison to the much simpler MV algorithm in the case of MCAO. 3. Sparse predictive Minimum Variance control algorithm for MCAO. The temporal prediction stage has been added to the non-dynamic MV control algorithm in such a way that no additional computational burden is introduced. It has been confirmed through simulations that the use of phase prediction makes it possible to significantly reduce the system sampling rate and thus overall computational complexity while both maintaining the system stable and effectively compensating for the measurement and control latencies.

Pelvic radiography in ATLS algorithms: A diminishing role?

ABSTRACT: BACKGROUND: Pelvic x-ray is a routine part of the primary survey of polytraumatized patients according to Advanced Trauma Life Support (ATLS) guidelines. However, pelvic CT is the gold standard imaging technique in the diagnosis of pelvic fractures. This study was conducted to confirm the safety of a modified ATLS algorithm omitting pelvic x-ray in hemodynamically stable polytraumatized patients with clinically stable pelvis in favour of later pelvic examination by CT scan. METHODS: We conducted a retrospective analysis of all polytraumatized patients in our emergency room between 01.07.2004 and 31.01.2006. Inclusion criteria were blunt abdominal trauma, initial hemodynamic stability and a stable pelvis on clinical examination. We excluded patients requiring immediate intervention because of hemodynamic instability. RESULTS: We reviewed the records of n = 452 polytraumatized patients, of which n = 91 fulfilled inclusion criteria (56% male, mean age = 45 years). The mechanism of trauma included 43% road traffic accidents, 47% falls. In 68/91 (75%) patients, both a pelvic x-ray and a CT examination were performed; the remainder had only pelvic CT. In 6/68 (9%) patients, pelvic fracture was diagnosed by pelvic x-ray. None of these 6 patients was found having a false positive pelvic x-ray, i.e. there was no fracture on pelvic CT scan. In 3/68 (4%) cases a fracture was missed in the pelvic x-ray, but confirmed on CT (false negative on x-ray). None of the diagnosed fractures needed an immediate therapeutic intervention. 5 (56%) were classified type A fractures, and another 4 (44%) B 2.1 in computed tomography (AO classification). One A 2.1 fracture was found in a clinically stable patient who only received CT scan (1/23). CONCLUSION: While pelvic x-ray is an integral part of ATLS assessment, this retrospective study suggests that in hemodynamically stable patients with clinically stable pevis, its sensitivity is only 67% and it may safely be omitted in favor of a pelvic CT examination if such is planned in adjunct assessment and available. The results support the safety and utility of our modified ATLS algorithm. A randomized controlled trial using the algorithm can safely be conducted to confirm the results.

Effect of high order interpolation in the stability and efficiency of the time-integration process in vorticity-velocity CFD algorithms

The numerical solution of the incompressible Navier-Stokes Equations offers an effective alternative to the experimental analysis of Fluid-Structure interaction i.e. dynamical coupling between a fluid and a solid which otherwise is very complex, time consuming and very expensive. To have a method which can accurately model these types of mechanical systems by numerical solutions becomes a great option, since these advantages are even more obvious when considering huge structures like bridges, high rise buildings, or even wind turbine blades with diameters as large as 200 meters. The modeling of such processes, however, involves complex multiphysics problems along with complex geometries. This thesis focuses on a novel vorticity-velocity formulation called the KLE to solve the incompressible Navier-stokes equations for such FSI problems. This scheme allows for the implementation of robust adaptive ODE time integration schemes and thus allows us to tackle the various multiphysics problems as separate modules. The current algorithm for KLE employs a structured or unstructured mesh for spatial discretization and it allows the use of a self-adaptive or fixed time step ODE solver while dealing with unsteady problems. This research deals with the analysis of the effects of the Courant-Friedrichs-Lewy (CFL) condition for KLE when applied to unsteady Stoke’s problem. The objective is to conduct a numerical analysis for stability and, hence, for convergence. Our results confirmthat the time step ∆t is constrained by the CFL-like condition ∆t ≤ const. hα, where h denotes the variable that represents spatial discretization.