Reduced Bayesian Hierarchical Models: Estimating Health Effects of Simultaneous Exposure to Multiple Pollutants

Quantifying the health effects associated with simultaneous exposure to many air pollutants is now a research priority of the US EPA. Bayesian hierarchical models (BHM) have been extensively used in multisite time series studies of air pollution and health to estimate health effects of a single pollutant adjusted for potential confounding of other pollutants and other time-varying factors. However, when the scientific goal is to estimate the impacts of many pollutants jointly, a straightforward application of BHM is challenged by the need to specify a random-effect distribution on a high-dimensional vector of nuisance parameters, which often do not have an easy interpretation. In this paper we introduce a new BHM formulation, which we call "reduced BHM", aimed at analyzing clustered data sets in the presence of a large number of random effects that are not of primary scientific interest. At the first stage of the reduced BHM, we calculate the integrated likelihood of the parameter of interest (e.g. excess number of deaths attributed to simultaneous exposure to high levels of many pollutants). At the second stage, we specify a flexible random-effect distribution directly on the parameter of interest. The reduced BHM overcomes many of the challenges in the specification and implementation of full BHM in the context of a large number of nuisance parameters. In simulation studies we show that the reduced BHM performs comparably to the full BHM in many scenarios, and even performs better in some cases. Methods are applied to estimate location-specific and overall relative risks of cardiovascular hospital admissions associated with simultaneous exposure to elevated levels of particulate matter and ozone in 51 US counties during the period 1999-2005.

The neurophysiological time pattern of illusionary visual perceptual transitions: a simultaneous EEG and fMRI study

Several divergent cortical mechanisms generating multistability in visual perception have been suggested. Here, we investigated the neurophysiologic time pattern of multistable perceptual changes by means of a simultaneous recording with electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Volunteers responded to the subjective perception of a sudden change between stable patterns of illusionary motion (multistable transition) during a stroboscopic paradigm. We found a global deceleration of the EEG frequency prior to a transition and an occipital-accentuated acceleration after a transition, as obtained by low-resolution electromagnetic tomography analysis (LORETA) analysis. A decrease in BOLD response was found in the prefrontal cortex before, and an increase after the transitions was observed in the right anterior insula, the MT/V5 regions and the SMA. The thalamus and left superior temporal gyrus showed a pattern of decrease before and increase after transitions. No such temporal course was found in the control condition. The multimodal approach of data acquisition allows us to argue that the top-down control of illusionary visual perception depends on selective attention, and that a diminution of vigilance reduces selective attention. These are necessary conditions to allow for the occurrence of a perception discontinuity in absence of a physical change of the stimulus.

Simultaneous determination of 3-hydroxyanthranilic and cinnabarinic acid by high-performance liquid chromatography with photometric or electrochemical detection

A convenient and rapid method for the simultaneous determination by HPLC of 3-hydroxyanthranilic acid and the dimer derived by its oxidation, cinnabarinic acid, is described. Buffers or biological samples containing these two Trp metabolites were acidified to pH 2.0 and extracted with ethyl acetate with recoveries of 96.5 +/- 0.5 and 93.4 +/- 3.7% for 3-hydroxyanthranilic and cinnabarinic acid, respectively. The two compounds were separated on a reversed-phase (C18) column combined with ion-pair chromatography and detected photometrically or electrochemically. The method was applied successfully to biological systems in which formation of either 3-hydroxyanthranilic or cinnabarinic acid had been described previously. Thus, interferon-gamma-treated human peripheral blood mononuclear cells formed and released significant amounts of 3-hydroxyanthranilic acid into the culture medium and mouse liver nuclear fraction possessed high "cinnabarinic acid synthase" activity. In contrast, addition of 3-hydroxyanthranilic acid to human erythrocytes resulted in only marginal formation of cinnabarinic acid. We conclude that the method described is specific, sensitive, and suitable for the detection of the two Trp metabolites in biological systems.

Early implant placement with simultaneous guided bone regeneration following single-tooth extraction in the esthetic zone: a cross-sectional, retrospective study in 45 subjects with a 2- to 4-year follow-up

BACKGROUND: The concept of early implant placement is a treatment option in postextraction sites of single teeth in the anterior maxilla. Implant placement is performed after a soft tissue healing period of 4 to 8 weeks. Implant placement in a correct three-dimensional position is combined with a simultaneous guided bone regeneration procedure to rebuild esthetic facial hard and soft tissue contours. METHODS: In this retrospective, cross-sectional study, 45 patients with an implant-borne single crown in function for 2 to 4 years were recalled for examination. Clinical and radiologic parameters, routinely used in implant studies, were assessed. RESULTS: All 45 implants were clinically successful according to strict success criteria. The implants demonstrated ankylotic stability without signs of a peri-implant infection. The peri-implant soft tissues were clinically healthy as indicated by low mean plaque (0.42) and sulcus bleeding index (0.51) values. None of the implants revealed a mucosal recession on the facial aspect as confirmed by a clearly submucosal position of all implant shoulders. The mean distance from the mucosal margin to the implant shoulder was -1.93 mm on the facial aspect. The periapical radiographs showed stable peri-implant bone levels, with a mean distance between the implant shoulder and the first bone-implant contact of 2.18 mm. CONCLUSIONS: This retrospective study demonstrated successful treatment outcomes for all 45 implants examined. The mid-term follow-up of 2 to 4 years also showed that the risk for mucosal recession was low with this treatment concept. Prospective clinical studies are required to confirm these encouraging results.

Venous thromboembolism and occult malignancy: simultaneous detection during pulmonary CT angiography with CT venography

OBJECTIVE: We explored the potential for patients with proven venous thromboembolism or pulmonary embolism (PE) to have occult malignancies detected during the same CT examination. To verify this, we compared the presence of occult malignancies identified on pulmonary artery CT angiography (CTA) and CT venography (CTV) when venous thromboembolism (VTE) was present. SUBJECTS AND METHODS: Pulmonary artery CTA combined with CTV was performed on a 16-MDCT scanner on 186 adult patients suspected of having pulmonary embolism without any known malignancies. CTV was performed from the diaphragm to the knee 180 seconds after CTA. Two radiologists evaluated the presence of VTE, that is PE or deep venous thrombosis (DVT), and tumor lesions on both examinations in consensus. The malignant nature of the possibly identified tumors was confirmed by pathologic examination. RESULTS: VTE was found in 49 patients (26%). Malignant tumors were detected in 24 patients (13%). Eleven patients with malignant tumors had VTE (46% of patients with malignant tumors; 22% with VTE and 6% of all patients). There was correlation with presence of malignancies between both and DVT and DVT associated with PE but not between presence of malignancies and PE only. Patients with DVT and those with DVT associated with PE had a risk ratio of 3.2 and 3.3, respectively, for having a malignant tumor discovered simultaneously. CONCLUSION: A high number of malignant tumors can be incidentally discovered on pulmonary artery CTA, even more so with additional CTV. Radiologists should scrutinize scans to pick up unknown malignancies, especially in patients with identified VTE.

Simultaneous subacute coronary drug-eluting stent thrombosis in two different vessels of a patient with factor V Leiden mutation

We review the case of a 46-year-old man who underwent elective percutaneous coronary intervention and stenting of the left anterior descending artery and right coronary artery with two sirolimus- and paclitaxel-eluting stents. Four days after angioplasty, he was readmitted with cardiogenic shock due to acute anterior and inferior myocardial infarction. Coronary angiography revealed subacute thrombosis of both stents, and balloon dilation was performed successfully thereafter. The follow-up investigations revealed that the patient was a carrier of factor V Leiden. We hereby discuss the importance of factor V Leiden as the most common cause of hypercoagulable state and its probable role in acute and subacute coronary stent thrombosis in drug-eluting stents.

Comparison of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using inversion recovery and fast T1 mapping sequences

The delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique has shown promising results in pilot clinical studies of early osteoarthritis. Currently, its broader acceptance is limited by the long scan time and the need for postprocessing to calculate the T1 maps. A fast T1 mapping imaging technique based on two spoiled gradient echo images was implemented. In phantom studies, an appropriate flip angle combination optimized for center T1 of 756 to 955 ms yielded excellent agreement with T1 measured using the inversion recovery technique in the range of 200 to 900 ms, of interest in normal and diseased cartilage. In vivo validation was performed by serially imaging 26 hips using the inversion recovery and the Fast 2 angle T1 mapping techniques (center T1 756 ms). Excellent correlation with Pearson correlation coefficient R2 of 0.74 was seen and Bland-Altman plots demonstrated no systematic bias.

Development and simultaneous application of multiple care protocols in critical care: a multicenter feasibility study

OBJECTIVE: To test the feasibility of and interactions among three software-driven critical care protocols. DESIGN: Prospective cohort study. SETTING: Intensive care units in six European and American university hospitals. PATIENTS: 174 cardiac surgery and 41 septic patients. INTERVENTIONS: Application of software-driven protocols for cardiovascular management, sedation, and weaning during the first 7 days of intensive care. MEASUREMENTS AND RESULTS: All protocols were used simultaneously in 85% of the cardiac surgery and 44% of the septic patients, and any one of the protocols was used for 73 and 44% of study duration, respectively. Protocol use was discontinued in 12% of patients by the treating clinician and in 6% for technical/administrative reasons. The number of protocol steps per unit of time was similar in the two diagnostic groups (n.s. for all protocols). Initial hemodynamic stability (a protocol target) was achieved in 26+/-18 min (mean+/-SD) in cardiac surgery and in 24+/-18 min in septic patients. Sedation targets were reached in 2.4+/-0.2h in cardiac surgery and in 3.6 +/-0.2h in septic patients. Weaning protocol was started in 164 (94%; 154 extubated) cardiac surgery and in 25 (60%; 9 extubated) septic patients. The median (interquartile range) time from starting weaning to extubation (a protocol target) was 89 min (range 44-154 min) for the cardiac surgery patients and 96 min (range 56-205 min) for the septic patients. CONCLUSIONS: Multiple software-driven treatment protocols can be simultaneously applied with high acceptance and rapid achievement of primary treatment goals. Time to reach these primary goals may provide a performance indicator.

SPATIAL UNDERSTANDING OF MATRIX INVERSION FOR INVERSE FORCE ESTIMATION

A basic approach to study a NVH problem is to break down the system in three basic elements – source, path and receiver. While the receiver (response) and the transfer path can be measured, it is difficult to measure the source (forces) acting on the system. It becomes necessary to predict these forces to know how they influence the responses. This requires inverting the transfer path. Singular Value Decomposition (SVD) method is used to decompose the transfer path matrix into its principle components which is required for the inversion. The usual approach to force prediction requires rejecting the small singular values obtained during SVD by setting a threshold, as these small values dominate the inverse matrix. This assumption of the threshold may be subjected to rejecting important singular values severely affecting force prediction. The new approach discussed in this report looks at the column space of the transfer path matrix which is the basis for the predicted response. The response participation is an indication of how the small singular values influence the force participation. The ability to accurately reconstruct the response vector is important to establish a confidence in force vector prediction. The goal of this report is to suggest a solution that is mathematically feasible, physically meaningful, and numerically more efficient through examples. This understanding adds new insight to the effects of current code and how to apply algorithms and understanding to new codes.

Simultaneous, bilateral anterior ischemic optic neuropathy (AION) in polycythemia vera: a case report

BACKGROUND: Polycythemia vera (PV) is a hemopoetic disorder. Apparently, although thrombosis accounts for the majority of morbidity, AION has not been associated with PV so far. PATIENT AND FINDINGS: A 63 y-old woman with PV was hospitalized because of acute liver failure. She also experienced bilateral painless loss of vision. Bilateral, pale optic disc swelling with flame-like hemorrhages, more pronounced in the right eye, constricted visual fields, and relative afferent papillary defect (RAPD) on the right side were present. Computer tomography scan revealed no signs of intraorbital pathology, elevated intracranial pressure or hemorrhages. CLINICAL COURSE: We interpreted the findings as AION associated with the hyperviscosity syndrome. Liver transplantation had to be carried out in the next days. Three weeks later, vision improved slightly, but RAPD persisted, and disc pallor developed in both eyes. The patient died two months later. DISCUSSION: Central retinal artery and vein occlusions have been described as complications of Essential thrombocythemia, but not of PV. We observed a rare case of bilateral neuropathy suggestive of AION. This condition has so far not been associated with PV.

TUNING, AVO, AND FLAT-SPOT EFFECTS IN A SEISMIC ANALYSIS OF NORTH SEA BLOCK F3

Reflection seismic data from the F3 block in the Dutch North Sea exhibits many large-amplitude reflections at shallow horizons, typically categorized as “brightspots ” (Schroot and Schuttenhelm, 2003), mainly because of their bright appearance. In most cases, these bright reflections show a significant “flatness” contrasting with local structural trends. While flatspots are often easily identified in thick reservoirs, we have often occasionally observed apparent flatspot tuning effects at fluid contacts near reservoir edges and in thin reservoir beds, while only poorly understanding them. We conclude that many of the shallow large-amplitude reflections in block F3 are dominated by flatspots, and we investigate the thin-bed tuning effects that such flatspots cause as they interact with the reflection from the reservoir’s upper boundary. There are two possible effects to be considered: (1) the “wedge-model” tuning effects of the flatspot and overlying brightspots, dimspots, or polarity-reversals; and (2) the stacking effects that result from possible inclusion of post-critical flatspot reflections in these shallow sands. We modeled the effects of these two phenomena for the particular stratigraphic sequence in block F3. Our results suggest that stacking of post-critical flatspot reflections can cause similar large-amplitude but flat reflections, in some cases even causing an interface expected to produce a ‘dimspot’ to appear as a ‘brightspot’. Analysis of NMO stretch and muting shows the likely exclusion of critical offset data in stacked output. If post-critical reflections are included in stacking, unusual results will be observed. In the North Sea case, we conclude the tuning effect was the primary reason causing for the brightness and flatness of these reflections. However, it is still important to note that care should be taken while applying muting on reflections with wide range of incidence angles and the inclusion of critical offset data may cause some spurious features in the stacked section.

Visual vector inversion during memory antisaccades--a TMS study

In the memory antisaccade task, subjects are instructed to look at an imaginary point precisely at the opposite side of a peripheral visual stimulus presented short time previously. To perform this task accurately, the visual vector, i.e., the distance between a central fixation point and the peripheral stimulus, must be inverted from one visual hemifield to the other. Recent data in humans and monkeys suggest that the posterior parietal cortex (PPC) might be critically involved in the process of visual vector inversion. In the present study, we investigated the temporal dynamics of visual vector inversion in the human PPC by using transcranial magnetic stimulation (TMS). In six healthy subjects, single pulse TMS was applied over the right PPC during a memory antisaccade task at four different time intervals: 100 ms, 217 ms, 333 ms, or 450 ms after target onset. The results indicate that for rightward antisaccades, i.e., when the visual target was presented in the left screen-half, TMS had a significant effect on saccade gain when applied 100 ms after target onset, but not later. For leftward antisaccades, i.e., when the visual target was presented in the right screen-half, a significant TMS effect on gain was found for the 333 ms and 450 ms conditions, but not for the earlier ones. This double dissociation of saccade gain suggests that the initial process of vector inversion can be disrupted 100 ms after onset of the visual stimulus and that TMS interfered with motor saccade planning based on an inversed vector signal at 333 ms and 450 ms after stimulus onset.