Various disease conditions can alter EEG event-related responses and fMRI-BOLD signals. We hypothesized that event-related responses and their clinical alterations are imprinted in the EEG spectral domain as event-related (spatio)spectral patterns (ERSPat). We tested four EEG-fMRI fusion models utilizing EEG power spectra fluctuations (i.e., absolute spectral model - ASM; relative spectral model - RSM; absolute spatiospectral model - ASSM; and relative spatiospectral model - RSSM) for fully automated and blind visualization of task-related neural networks. Two (spatio)spectral patterns (high δ ₄ band and low β ₁ band) demonstrated significant negative linear relationship (p _FWE < 0.05) to the frequent stimulus and three patterns (two low δ ₂ and δ ₃ bands, and narrow θ ₁ band) demonstrated significant positive relationship (p < 0.05) to the target stimulus. These patterns were identified as ERSPats. EEG-fMRI F-map of each δ ₄ model showed strong engagement of insula, cuneus, precuneus, basal ganglia, sensory-motor, motor and dorsal part of fronto-parietal control (FPCN) networks with fast HRF peak and noticeable trough. ASM and RSSM emphasized spatial statistics, and the relative power amplified the relationship to the frequent stimulus. For the δ ₄ model, we detected a reduced HRF peak amplitude and a magnified HRF trough amplitude in the frontal part of the FPCN, default mode network (DMN) and in the frontal white matter. The frequent-related β ₁ patterns visualized less significant and distinct suprathreshold spatial associations. Each θ ₁ model showed strong involvement of lateralized left-sided sensory-motor and motor networks with simultaneous basal ganglia co-activations and reduced HRF peak and amplified HRF trough in the frontal part of the FPCN and DMN. The ASM θ ₁ model preserved target-related EEG-fMRI associations in the dorsal part of the FPCN. For δ ₄, β ₁, and θ ₁ bands, all models provided high local F-statistics in expected regions. The most robust EEG-fMRI associations were observed for ASM and RSSM.

Keywords: GLM; general linear model; independent component analysis; simultaneous EEG-fMRI; spectral and spatiospectral models; task-related network visualization; visual oddball paradigm.

This article is a review of the role of mast cells and other inflammatory cells in pathogenesis of chronic urticaria. The role of histamine in pathophysiology of chronic urticaria has been established but interaction between IgE-bound mast cells and allergen is unlikely to be the mechanism by which histamine release occurs. The authors present some factors trigger mast cell degranulation and mediator release as histamine releasing factor (HRF) generating by lymphocytes and IgE autoantibodies against mast cell and basophil IgE receptors.

We propose a framework for studying the electrophysiological correlates of BOLD-fMRI. This framework relies on structured coupled matrix-tensor factorization (sCMTF), a joint multidimensional decomposition which reveals dynamical interactions between LFP/EEG oscillatory features and BOLD-fMRI data. We test whether LFP/EEG-BOLD co-fluctuations and regional hemodynamic response functions can be estimated by sCMTF using whole-brain modelling of restingstate activity. We produce permuted datasets to show that our framework extracts EEG/LFP temporal patterns that correlate significantly with BOLD signal fluctuations. Our framework is also capable of estimating HRFs that accurately embodies simulated hemodynamics, with a word of caution regarding initialization of the sCMTF algorithm.

Standard methods for the analysis of functional MRI data strongly rely on prior implicit and explicit hypotheses made to simplify the analysis. In this work the attention is focused on two such commonly accepted hypotheses: (i) the hemodynamic response function (HRF) to be searched in the BOLD signal can be described by a specific parametric model e.g., double-gamma; (ii) the effect of stimuli on the signal is taken to be linearly additive. While these assumptions have been empirically proven to generate high sensitivity for statistical methods, they also limit the identification of relevant voxels to what is already postulated in the signal, thus not allowing the discovery of unknown correlates in the data due to the presence of unexpected hemodynamics. This paper tries to overcome these limitations by proposing a method wherein the HRF is learned directly from data rather than induced from its basic form assumed in advance. This approach produces a set of voxel-wise models of HRF and, as a result, relevant voxels are filterable according to the accuracy of their prediction in a machine learning framework. This approach is instantiated using a temporal architecture based on the paradigm of Reservoir Computing wherein a Liquid State Machine is combined with a decoding Feed-Forward Neural Network. This splits the modeling into two parts: first a representation of the complex temporal reactivity of the hemodynamic response is determined by a universal global "reservoir" which is essentially temporal; second an interpretation of the encoded representation is determined by a standard feed-forward neural network, which is trained by the data. Thus the reservoir models the temporal state of information during and following temporal stimuli in a feed-back system, while the neural network "translates" this data to fit the specific HRF response as given, e.g. by BOLD signal measurements in fMRI. An empirical analysis on synthetic datasets shows that the learning process can be robust both to noise and to the varying shape of the underlying HRF. A similar investigation on real fMRI datasets provides evidence that BOLD predictability allows for discrimination between relevant and irrelevant voxels for a given set of stimuli.

OBJECTIVE

To evaluate dose response of inhaled nitric oxide (iNO) for surfactant-treated rabbits with meconium aspiration-induced acute lung injury (ALI) and hypoxemic respiratory failure (HRF), and variation of measured iNO by continuous NO delivery in pressure support ventilation (PSV).

METHODS

Adult rabbits (2.0 - 3.5 kg, n = 33) were randomized to receive intratracheal meconium instillation for 30 min and subjected to following treatment (n = 6 - 8). There were 4 groups: Control (C); NO, iNO at 1, 10, 20 and 40 x 10(-6) each for 60 min at 30 min interval of disconnection; Surf, intratracheal instillation of porcine lung surfactant phospholipids (100 mg/kg); SNO, both iNO and surfactant as in the NO and Surf groups; and a normal group (N), which did not undergo meconium aspiration but received sham deliveries of normal saline. All the animals were treated with PSV for 6 h. iNO levels at different input and sampling sites in the NO and SNO groups were detected by on-line chemiluminescent technique. The blood gas and lung mechanics were measured during the experiments every 2 h.

RESULTS

(1) Meconium aspiration induced ALI and severe HRF (PaO(2)/FiO(2) < 200 mmHg) and depressed dynamic compliance of respiratory system (Cdyn) and airway resistance (Raw). In both Surf and NO groups modestly improved oxygenation was observed. In the SNO, values for PaO(2)/FiO(2) were improved from (185 +/- 39) mmHg at baseline to (301 +/- 123) mmHg at 6 h, while moderate or transient improvement was observed in both Surf and NO groups. Cdyn and Raw were only improved for short time in the Surf, NO and SNO groups. iNO had a mild response at 1 x 10(-6) to good response at 10 and 20 x 10(-6), but no further improvement occurred at 40 x 10(-6). The response of iNO in NO group was relatively transient compared to the SNO group. (2) When iNO was connected to the ventilator circuit, the connected site should be placed before humidifier to minimize fluctuation of iNO concentration, and sampling site for iNO monitoring should be placed adequately to eliminate artifact.

CONCLUSIONS

iNO synergistically improved surfactant effects on oxygenation and lung mechanics. Continuous supply of iNO with non-continuous flow ventilator provided stable NO within accepted target range with least variation.

Hydroxyl radical footprinting (HRF) has been successfully used to study the structure of both nucleic acids and proteins. The method utilizes hydroxyl radicals to oxidize solvent accessible sites in macromolecules. In recent years, the method has shown some utility for live cell analysis. In this review, we will survey the current state of the field for footprinting macromolecules in living cells. The field is relatively new, particularly for protein studies, with only a few publications on the development and application of HRF on live cells. DNA-protein interaction sites and information on the secondary and tertiary structure of RNA has been characterized. In addition, the conformational changes of membrane-spanning channels upon opening and activation have also been studied by in-cell HRF. In this review, we highlight examples of these applications.

Hydroxyl-radical footprinting (HRF) is a powerful method for probing structures of nucleic acid-protein complexes with single-nucleotide resolution in solution. To tap the full quantitative potential of HRF, we describe a protocol, hydroxyl-radical footprinting interpretation for DNA (HYDROID), to quantify HRF data and integrate them with atomistic structural models. The stages of the HYDROID protocol are extraction of the lane profiles from gel images, quantification of the DNA cleavage frequency at each nucleotide and theoretical estimation of the DNA cleavage frequency from atomistic structural models, followed by comparison of experimental and theoretical results. Example scripts for each step of HRF data analysis and interpretation are provided for several nucleosome systems; they can be easily adapted to analyze user data. As input, HYDROID requires polyacrylamide gel electrophoresis (PAGE) images of HRF products and optionally can use a molecular model of the DNA-protein complex. The HYDROID protocol can be used to quantify HRF over DNA regions of up to 100 nucleotides per gel image. In addition, it can be applied to the analysis of RNA-protein complexes and free RNA or DNA molecules in solution. Compared with other methods reported to date, HYDROID is unique in its ability to simultaneously integrate HRF data with the analysis of atomistic structural models. HYDROID is freely available. The complete protocol takes ~3 h. Users should be familiar with the command-line interface, the Python scripting language and Protein Data Bank (PDB) file formats. A graphical user interface (GUI) with basic functionality (HYDROID_GUI) is also available.

The translationally controlled tumor protein (TCTP), initially identified as a tumor- and growth-related protein, is also known as a histamine-releasing factor (HRF). TCTP is widely distributed in the neuronal systems, but its function is largely uncharacterized. Here, we report a novel function of TCTP in the neurotransmitter release from a neurosecretory, pheochromocytoma (PC12) cells. Treatment with recombinant TCTP (rTCTP) enhanced both basal and depolarization (50 mM KCl)-evoked [³H]dopamine release in concentration- and time-dependent manners. Interestingly, even though rTCTP induced the increase in intracellular calcium levels ([Ca2+]i), the rTCTP-driven effect on dopamine release was mediated by a Ca2+-independent pathway, as evidenced by the fact that Ca2+-modulating agents such as Ca2+ chelators and a voltage-gated L-type Ca2+-channel blocker did not produce any changes in rTCTP-evoked dopamine release. In a study to investigate the involvement of phospholipase A₂ (PLA₂) in rTCTP-induced dopamine release, the inhibitor for Ca2+-independent PLA₂ (iPLA₂) produced a significant inhibitory effect on rTCTP-induced dopamine release, whereas this release was not significantly inhibited by Ca2+-dependent cytosolic PLA₂ (cPLA₂) and secretory PLA₂ (sPLA₂) inhibitors. We found that rTCTP-induced dopamine release from neuronal PC12 cells was modulated by a Ca2+-independent mechanism that involved PLA₂ in the process, suggesting the regulatory role of TCTP in the neuronal functions.

Resistance to methyl benzimidazole carbamates (MBCs) in Monilinia fructicola, the causal agent of brown rot of stone fruits, is known to be present in South Carolina peach orchards, but the molecular mechanism of resistance has not been investigated. Nine isolates were collected from peach in five counties in South Carolina and examined in petri dish assays on potato dextrose agar (PDA) for resistance to the MBC fungicide thiophanate-methyl (Topsin-M 70WP; Ceraxagri, King of Prussia, PA) at the discriminatory dose of 50 μg/ml. Isolates that grew on the fungicide-amended medium were considered highly resistant (HR). The β-tubulin gene from four sensitive (S) and five HR M. fructicola isolates was PCR-amplified with primer pair TubA and TubR1 as described previously (1). Sequence analysis revealed several silent mutations in introns and exons in S and HR isolates and the presence of the previously described E198A allele in HR but not S isolates (1). Nucleotide sequences of the β-tubulin gene from three S (BS, S2, MfEgpc1) and two HR isolates (MfPdt6 and BR2) were submitted to GenBank under accession numbers HM051379, HM051380, HM051381, HM051382, and HM051383, respectively. To our knowledge, this is the first report of the E198A in M. fructicola isolates from South Carolina and the East Coast. This allele is responsible for high levels of MBC resistance in M. fructicola (1). A previously reported PCR-based method using primers HRF+HRR designed to detect the E198A mutation in M. fructicola HR isolates (1) was improved by adding primer TR739 (5'-TCA CGA CGA ACA ACA TCA AGA-3') to the PCR cocktail. This additional internal primer amplified a 222-bp fragment from all S and HR isolates and therefore provided a useful, additional control. The confirmation of the E198A allele in M. fructicola isolates provides another useful tool to detect MBC resistance in commercial peach orchards in South Carolina. Reference: (1) Z. H. Ma et al. Appl. Environ. Microbiol. 69:7145, 2003.

Total kininogen (Kgn), kallikrein, and prekallikrein were measured in patients with malignant hypertension (MH), essential hypertension (EH), normotensive control (NC), and hypertension and chronic renal failure (HRF). These components of the kallikrein-kinin system were related to the levels of creatinine and fibrinogen. High molecular weight Kgn and low molecular weight Kgn were also measured in blood samples from a peripheral vein, arterial blood, and suprahepatic vein in NC, EH, and MH. Results showed that total Kgn levels were diminished in MH and this diminution could not be ascribed to decreases in renal function, hematocrit, or fibrinogen levels. Appropriate antihypertensive treatment for over 1 year did not normalize Kgn levels in 10 of 11 patients. High molecular weight Kgn and low molecular weight Kgn were both diminished in MH (0.26 +/- 0.04 nmol bradykinin/ml and 0.93 +/- 0.12 nmol lysyl-bradykinin/ml, respectively) as compared to NC (0.39 +/- 0.07 and 1.92 +/- 0.16) and EH (0.51 +/- 0.07 and 1.65 +/- 0.13). Higher concentrations of high molecular weight Kgn were demonstrated in the suprahepatic vein as compared to arterial blood, demonstrating its synthesis by the liver. However, patients with MH had a diminished capacity to synthetize high molecular weight Kgn. A decrease in synthesis of high molecular weight Kgn may be a partial explanation for low levels of total Kgn. It is suggested that a lack of Kgn may play a role in the pathogenesis of MH.

OBJECTIVE

To discuss the influence of retinal detachment (RD) surgery on the blood flow of retina and optic nerve head.

METHODS

Heidelberg Retina Flowmeter (HRF) was used to measure the blood flow of retina and optic nerve head in 62 eyes of 62 patients with postoperative rhegmatogenous RD surgery, including 34 eyes having undertaken vitreoretinal (VR) surgery and 28 eyes, scleral buckling (SB) surgery. Operative methods included scleral encircling procedure, cryotherapy, lensectomy, vitrectomy, perfluorodeclin liquid application, endolaser and C(2)F(6) gas or silicone oil tamponade.

RESULTS

The blood flow volume (VOL), blood flow velocity (FLW) and the erythrocyte flow velocity (VEL) of fundus in the postoperative RD eyes were reduced in the comparison with those of the fellow control eyes. The VEL of temporal and nasal papillary disk rim had significant differences (P < 0.05). The VOL, FLW and VEL of the papillary vessel, VOL and FLW of temporal and nasal papillary disk rim, VOL of temporal and nasal juxtapapillary retina in the operative eyes were lower than those of the fellow eyes (P < 0.01). In the comparison between the eyes having undertaken VR surgery and the eyes undertaken SB surgery, the VOL, FLW and VEL of VR surgery were reduced more than those of SB surgery. The VEL of temporal and nasal papillary disk rim and nasal juxtapapillary retina and FLW of temporal juxtapapillary retina had significant differences (P < 0.05). VOL, FLW and VEL of silicone oil tamponade eyes were reduced more than those in the operative eyes without silicone oil tamponade. VOL of nasal papillary disk rim and juxtapapillary retina had significant differences (P < 0.05). VOL and VEL of temporal papillary disk rim, VOL of temporal juxtapapillary retina had very significant differences (P < 0.01).

CONCLUSIONS

VR surgery and SB surgery of RD influence papillary and retinal VOL, FLW, VEL. The influence of VR surgery on the fundus blood flow is more significant than that of SB surgery. The silicone oil tamponade also influences the VOL and VEL of the fundus.

The aim of the article is to study actual ration of patients suffered from hemorrhagic fever with renal syndrome (HFRS) and its interaction with the development of arterial hypertension (AH). 296 men aged 20–59 suffered from HFRS were under the care of physician within the period of 1 to 6 years. Among this group 49 cases of arterial hypertension have been registered after HFRS. Frequency method of food product consumption was used to define nutrition. A Russian questionnaire published by Institute of Nutrition (1997) was used. Actual nutrition in men suffered from HFRS is marked by basic nutrients unbalance that is: excessive cholesterol and fat consumption (due to saturated fatty acid), polyunsaturated fatty acid deficiency, sugar overuse and animal protein prevalence over vegetable proteins in patient ration. Atherogenic shift in a ration of patients with AH and suffered from HRFS has been exposed more strongly in all aged group but mostly evident in patients aged 40 and after. Alcohol consumption in men with AH and suffered from HFRS is higher than in healthy peers. Interaction between atherogenic unbalance on the main nutrients in patients with HFRS and arterial hypertension has been defined. Consumatory behavior correction is to be taken to prevent arterial hypertension in recovered patients suffered from HFRS.

The effect of riboflavin status on acetaminophen hepatotoxicity was determined in the rat. Groups of rats were fed one of the following diets: "riboflavin-free" (RFF), low riboflavin (LRF), high riboflavin (HRF), or high riboflavin pair-fed (HRF pair-fed) with RFF group. After riboflavin deficiency was established by determining erythrocyte glutathione reductase activity coefficient, rats in all groups were administered a toxic dose of acetaminophen (1 g/kg body weight) orally. Their controls were given the vehicle alone. All animals were killed 24 h later and hepatotoxicity was assessed by the elevation of serum transaminases and by a necrotic score based on histological examination. The RFF diet induced biochemical riboflavin deficiency, decreased food intake and body weight gain, and was associated with almost complete protection against acetaminophen toxicity. Rats on the LRF diet, with less severe riboflavin deficiency and no significant change in weight gain, showed some necrosis, but it was much less than in the HRF ad libitum-fed rats. The HRF pair-fed rats with no biochemical riboflavin deficiency but with considerable growth retardation also showed very little hepatic necrosis. Our results suggest that riboflavin deficiency protects rats against acetaminophen toxicity but it is confounded by decreased food consumption and body weight.

Peripheral-blood leucocytes from Dermatophagoides pteronyssinus- and/or Lolium perenne-allergic patients produce in vitro histamine-releasing factor (HRF) in an allergen-specific and concentration-dependent relationship. Maximum production of HRF occurred in cultures containing as little as 10-100 pg/ml crude allergen extract, although a second peak occurred at higher concentrations (10-100 micrograms/ml). While HRF was detectable in 1-hour cultures, maximal production required 24 h in culture. In contrast, HRF induced by streptokinase/streptodornase (SK/SD) was generally maximal after 1 h. Allergen-induced HRF production was almost exclusively associated with monocytes and B cells. In contrast, peripheral-blood T cells were the major source of induced HRF production in cultures containing SK/SD. Histamine-releasing cytokines are apparently produced by different cell populations, the activation of which may be dependent upon the characteristics of the stimulating antigen.

OBJECTIVE

The Second Multidisciplinary Forum: Parathyroid Hormone (PTH) Use in Osteoporotic Patients at High Risk for Fractures (HRF) was conducted to identify specific findings that would be helpful for defining high-risk status and guiding the use of parathyroid hormone 1-84 (PTH1-84) as an anabolic therapy in daily clinical practice. This article summarizes the conclusions from the meeting.

METHODS

Based on three typical case records, and the final conclusions from the first Forum (held in 2010), several questions were posed regarding daily clinical practice definitions of HRF and use of PTH1-84, through a series of 19 meetings throughout Spain. The main discussion topics and agreed conclusions were collected by meeting coordinators and shared at a meeting held in May 2011. After extensive discussions, which also included other organizational and educational matters, some newly agreed conclusions were reached.

RESULTS

The consensus was that an HRF patient is usually thought of as being elderly (aged >70 years), with a very low bone mass or a prevalent fracture, and some other associated risk factors. High-risk groups who were identified included patients with neurologic diseases, institutionalized individuals, and patients receiving long-term steroid therapy. PTH1-84 was considered a safe and effective drug, having added value because of its analgesic effect and good level of patient adherence. Opportunities for improved PTH1-84 use were identified, such as better patient selection and follow-up based on localization and specialty. Some improvement opportunities were also detected in organizational and educational areas.

CONCLUSIONS

The Forum identified differences between clinical recommendations and daily clinical practice. Some elements, involving both organizational and educational areas that could help to reduce such discrepancies, are described.

The previous research showed that slow sand filtration (SSF) can remove the total coli by approximately 99% because of the schmutzecke layer in the filter. The presented study aimed to complete the previous research on SSF, especially on the schmuztdecke layer mechanism, to remove total coli. Total coli is a parameter of water quality standard in Indonesia, and the behavior of schmutzdecke affects the total coli removal. In the present study, the raw water from Amprong River was treated using horizontal roughing filter (HRF) and SSF. The variations in SSF rate used were 0.2 and 0.4 m/h. Total coliforms were analyzed using the most probable number test, and schmutzdecke visualization was conducted through scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX). The best coliform concentration in water treated by the combination of HRF and SSF was 4,386 colonies per 100 mL of sample using the filtration rate of 0.2 m/h, and its removal efficiency was 99.60%. However, the quality of water treated by the combination of HRF and SSF did not meet the drinking water quality standard because the removal of total coli must be 100%. The SEM-EDX visualization results in schmutzdecke showed that the average bacteria in the schmutzdecke layer were small, white, opaque, and circular, with entire edge and flat elevation. The Gram test results showed that the schmutzdecke bacteria consisted of Gram-positive and Gram-negative bacteria with basil as the common cell form.

<AbstractText>Fabry disease (FD) is an X-linked inherited storage disorder caused by deficiency of lysosomal alpha-Galactosidase A. Here we describe new retinal findings in patients with FD assessed by Spectral domain optical coherence tomography (SD-OCT) and their possible clinical relevance.</AbstractText><AbstractText>54 eyes of 27 FD patients and 54 eyes of 27 control subjects were included. The ophthalmic examination included visual acuity testing, tonometry, slit lamp and fundus examination. SD-OCT imaging of the macula was performed in all subjects. Central retinal thickness and retinal nerve fiber layer analysis were quantified. Vessel tortuosity was obtained by a subjective scoring and mathematically calculated. Inner retinal hyperreflective foci (<em>HRF</em>) were quantified, clinically graded and correlated with a biomarker of Fabry disease (lyso-Gb3).</AbstractText><AbstractText>In comparison to an age-matched control group, a significant amount of <em>HRF</em> was identified in macular SD-OCT images in FD patients. These <em>HRF</em> were localized within the inner retinal layers. Furthermore, lyso-Gb3 levels correlated significantly with the quantitative evaluation of <em>HRF</em> (p < 0,001). In addition, the vessel tortuosity was remarkably increased in FD patients compared to control persons and correlated significantly with lyso-G3 levels (p = 0.005). A further subanalysis revealed significantly higher <em>HRF</em> and vessel tortuosity scores in male patients with the classic FD phenotype.</AbstractText><AbstractText>The observational, cross sectional, comparative study describes novel intraretinal findings in patients with FD. We were able to identify suspicious <em>HRF</em> within the inner retinal layers. These findings were not accompanied by functional limitations, as visual acuity remained unchanged. However, <em>HRF</em> correlated well with lyso-Gb3, a degradation product of the accumulating protein Gb3 and might potentially indicate Gb3 accumulation within the highly metabolic and densely vascularized macula.</AbstractText>

Introduction. Group iterative multiple model estimation (GIMME) has proven to be a reliable data-driven method to arrive at functional connectivity maps that represent associations between brain regions across time in groups and individuals. However, to date, GIMME has not been able to model time-varying task-related effects. This paper introduces HRF-GIMME, an extension of GIMME that enables the modeling of the direct and modulatory effects of a task on fMRI data collected using event-related designs. Critically, HRF-GIMME incorporates person-specific modeling of the hemodynamic response function (HRF) to accommodate known variability in onset delay and shape. Methods. Following an introduction of the technical aspects of HRF-GIMME, the performance of HRF-GIMME is evaluated via both a simulation study and application to empirical data. The simulation study assesses the sensitivity and specificity of HRF-GIMME using data simulated from one slow and two rapid event-related designs, and HRF-GIMME is then applied to two empirical data sets from similar designs to evaluate performance in recovering known neural circuitry. Results. HRF-GIMME showed high sensitivity and specificity across all simulated conditions, and performed well in the recovery of expected relations between convolved task vectors and brain regions in both simulated and empirical data, particularly for the slow event-related design. Conclusion. Results from simulated and empirical data indicate that HRF-GIMME is a powerful new tool for obtaining directed functional connectivity maps of intrinsic and task-related connections that is able to uncover what is common across the sample as well as crucial individual-level path connections and estimates.

Keywords: Event-related design; Functional connectivity; Modeling; Statistics.

To investigate, in the setting of stereotactic ablative radiation therapy (SABR) for early-stage non-small cell lung cancer, the incidence and patterns of change in high-risk radiologic features (HRFs) in patients known to have no local recurrence.

Computed tomography (CT) scans of patients treated using volumetric modulated arc therapy SABR between 2008 and 2013 were eligible if follow-up scans were available for 2 years and no local recurrences were diagnosed. All scans were reviewed at a workstation using an add-on tool for ClearCanvas (Synaptive Medical). Five clinicians who were blinded to clinical outcomes scored the presence of HRFs: enlarging opacity (EO), sequential enlarging opacity, enlarging opacity after 12 months (EO12), bulging margin, loss of linear margins, cranio-caudal growth, and loss of air bronchogram. After each review, clinicians recommended follow-up procedures based on published recommendations.

A total of 88 patients (747 CT scans) were evaluated. The HRFs most frequently recorded by ≥3 observers on at least 1 follow-up scan were EO (64.8%), EO12 (50.0%), and sequential enlarging opacity (13.6%). Fifty-six patients developed EO within the first year after SABR, and of these, 46 also developed subsequent EO (EO12). In 76 patients who developed EO after 1 year of follow-up, 30 had not manifested EO previously. Three or more HRFs have been associated with recurrences, and this was observed on CT scan in 22.7% of patients. In their routine care, 6 patients had undergone a positron emission tomography scan because of a suspected local recurrence, and 4 underwent an attempt at biopsy.

More than 50% of patients without a local recurrence after SABR develop HRFs. Because ≥3 HRFs were present in nearly 25% of patients, further refinement of follow-up recommendations are necessary.

OBJECTIVE

We tested a prototype stimulator interfaced with a commercially available scanning laser ophthalmoscope designed to measure retinal capillary perfusion (Heidelberg Retina Flowmeter (HRF)). The add-on stimulator optically superimposed the image of a monitor display on to the subject's retina coaxially with the imaging optics of the HRF. The purpose of the study was to determine if flicker and pattern stimulation presented in this manner could evoke changes in retinal perfusion that could be measured by the HRF.

METHODS

The prototype stimulator projected 55 degrees visual angle circular fields of homogeneous flicker, alternating checkerboard, and multi-focal m-sequence hexagonal patterns on the retina of 10 human subjects during acquisition of images by the HRF.

RESULTS

Images were successfully acquired and processed. HRF perfusion values during flicker and pattern stimulation were not significantly different from control values.

CONCLUSIONS

Results of the present study and a previously published study showing a flicker-induced increase in the HRF perfusion values are contradictory. Retinal perfusion measured by the HRF were not affected by flicker and pattern stimulation delivered through the prototype device. These data are not consistent with a large flicker or pattern induced increase in retinal perfusion. The instrumental modification appears promising. However, the raster scan stimulation technique or some other aspect of stimulation or image acquisition may account for the different results in the present study and previous studies in our laboratory and in the laboratories of other investigators.

Background: FMRI signal amplitude can change during stimulus presentation due to underlying neural function and hemodynamic responses limiting the accuracy of fMRI in pre-surgical planning. To account for these changes in fMRI activation signal, we used breath-hold tasks to mimic hemodynamic changes in brain tumor subjects and scaled the activation response. Methods: Motor and/or language fMRI was performed in 21 subjects with brain tumor. A breath-hold task was also performed in these subjects to obtain the hemodynamic response changes independent of neural changes. The task activation signals were calibrated on a voxel wise basis for all the subjects. Direct cortical stimulation was used to verify the scaled results of task-based fMRI. Results: After scaling for the hemodynamic response function (HRF) on a voxel wise basis, the spatial extent of the scaled activation was more clustered together and appeared to minimize false positives. Similarly, accounting for the underlying canonical HRF, the percentage increase of active voxels after scaling had lower standard non-deviation suggesting that the activation response across voxels were more similar. Conclusion: Although preliminary in nature, this study suggests that the variation in hemodynamic changes can be calibrated using breath-hold in brain tumor subjects and can also be used for other clinical cases where the underlying HRF has been altered.

Keywords: brain tumor; breath-hold; fMRI; hemodynamics; language; motor.

This paper examines the feasibility of accurate state classification of autonomic nervous activity (ANA) based on the power spectral pattern of the heart rate fluctuations (HRFs). Some attempts have been made to utilize artificial neural networks (ANNs) to classify HRFs for clinical diagnoses such as ischemic cardiomyopathy, arrhythmia or sleep apnea. To establish the firm bases for making such clinical diagnoses, it may be important to examine the classification accuracy for the data in physiologically well defined conditions by e.g. application of autonomic blocking agents. In this paper the three layered perceptron has been trained by the heart rate data in variety of ANS states yielded by the application of Atropine and Propranolol to 14 healthy male subjects. Six state (control, atropine and propranolol for each of the spine and upright posture) classification based on power spectrum showed average sensitivity of 67.2% and specificity 91.2%. Four state (control, atropine, propranolol and double block for either spine or upright posture) resulted in the average classification sensitivity of 75.7% and specificity 95.5%. The paper revealed that entropy bandwidth and indices originated from characteristic oscillations of blood pressure change improve the classification accuracy.