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Inversion of the left atrial appendage is a rare phenomenon and frequently occurs as a complication following cardiac operations. Spontaneous inversion is even rarer, and so far, only three cases have been reported. We report an additional case of spontaneous inversion in 4-month female with Down's syndrome, hypothyroidism, and complete atrioventricular canal defect.
In order to be able to solve the inverse problem of electrocardiography, the lead field matrix (transfer matrix) has to be calculated. The two methods applied for computing this matrix, which are compared in this study, are the boundary element method (BEM) and the finite element method (FEM). The performance of both methods using a spherical model was investigated. For a comparable discretization level, the BEM yields smaller relative errors compared to analytical solutions. The BEM needs less computation time, but a larger amount of memory. Inversely calculated myocardial activation times using either the FEM or BEM computed lead field matrices give similar activation time patterns. The FEM, however, is also capable of considering anisotropic conductivities. This property might have an impact for future development, when also individual myocardial fiber architecture can be considered in the inverse formulation.
The possibility of spectrum inversion has been debated since it was raised by and is still discussed because of its implications for functionalist theories of conscious experience (e.g., Palmer, 1999). This paper provides a mathematical formulation of the question of spectrum inversion and proves that such inversions, and indeed bijective scramblings of color in general, are logically possible. Symmetries in the structure of color space are, for purposes of the proof, irrelevant. The proof entails that conscious experiences are not identical with functional relations. It leaves open the empirical possibility that functional relations might, at least in part, be causally responsible for generating conscious experiences. Functionalists can propose causal accounts that meet the normal standards for scientific theories, including numerical precision and novel prediction; they cannot, however, claim that, because functional relationships and conscious experiences are identical, any attempt to construct such causal theories entails a category error.
OBJECTIVE: This study was performed to evaluate the clinical usefulness of the adventitial inversion technique in acute type A aortic dissection, with special attention to the impact of this procedure on the postoperative status of false lumen evaluated by computed tomographic scan. METHODS: From March 2001 to November 2004, 18 consecutive patients underwent emergent surgery for acute type A aortic dissection. Supracoronary graft replacement was performed in all the patients (ascending aorta/hemiarch replacement: 13/18=72%, total arch replacement: 5/18=28%). The adventitial inversion technique was used for both the proximal and the distal stump constructions of the dissected aortic wall without the aid of Teflon felt or biologic glue. Aortic regurgitation was treated with resuspension of the aortic commissures. RESULTS: There were two hospital deaths and the overall hospital mortality rate was 11.1%. The mean postoperative blood loss was 635+/-214 ml and no reexploration was required in any of the patients. Postoperative computed tomography showed closure of the false lumen in aortic root, aortic arch, and proximal descending thoracic aorta in all of the surviving patients. Postoperative echocardiography demonstrated no aortic regurgitation in any of the patients. Two patients died late postoperatively from unrelated causes to aortic dissection. The remaining 14 patients are doing well without a second-stage operation for aortic root or distal aortic lesions during the follow-up period of 7-51 months (mean: 28+/-14 months). CONCLUSIONS: The adventitial inversion technique provides an excellent immediate hemostasis and facilitates thrombotic closure of the proximal and the distal false lumen in the treatment for acute type A aortic dissection.
GABA(A) receptors containing alpha5 subunits have been suggested to mediate the rewarding effects of ethanol. We tested this hypothesis in mice with deletion of alpha5 subunits. alpha5 knockout mice did not differ from wildtypes in operant responding for 10% ethanol/10% sucrose, but responded less for 10% sucrose. The benzodiazepine (BZ) site inverse agonist, Ro 15-4513, has higher affinity for GABA(A) receptors containing 5 subunits and dose-dependently (0-27 mg/kg, i.p.) reduced lever pressing for ethanol/sucrose in wildtype mice, but had less effect in knockout mice; lever pressing for sucrose was unaffected. These data suggest that alpha5 subunits are not essential for ethanol reward, but the reduction of operant responding for ethanol by Ro 15-4513 is mediated by alpha5-containing GABA(A) receptors. In measures of ethanol consumption, alpha5 knockout mice did not differ from wildtypes at low ethanol concentrations (2-8%), but consumed less ethanol at higher concentrations; these differences were not attributable to increased behavioural disruption of the knockout by ethanol, since no differences were seen in sensitivity to ethanol's sedative or ataxic effects. Ro 15-4513's ability to reduce ethanol consumption was unaffected, suggesting that this effect is not mediated by the alpha5 subtype. Secondly, we tested the ability of a novel alpha5-efficacy-selective benzodiazepine receptor ligand, alpha5IA-II, that possesses greater inverse agonist activity at alpha5- than at alpha1-, á2- or alpha3-containing GABA(A) receptors, to influence operant responding. alpha5IA-II (0.03-3 mg/kg) dose-dependently decreased lever pressing for 10% ethanol, the minimally effective dose of 1 mg/kg, corresponding to over 90% receptor occupancy, but did not affect lever pressing for 4% sucrose. Although inverse agonists acting at alpha5-containing receptors reduce ethanol self-administration, alpha5 subunits may not be essential to signaling ethanol reward.
Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson's disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = -0.65, P < 0.001 and r = -0.33, P < 0.001 for activities over 13-30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD.
OBJECTIVE: To examine an unusual paracentric inversion of chromosome 7 found in an azoospermic man. DESIGN: Case report. SETTING: Infertility clinic at a private hospital. PATIENT(S): An azoospermic but otherwise apparently healthy man. INTERVENTION(S): Karyotyping with peripheral blood lymphocytes, microdissection testicular sperm extraction (TESE), and intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Sperm count and GBG banding. RESULTS: A karyogram revealed paracentric inversion of chromosome 7 with breakpoints at 7q22 and 7q31. Testicular histopathology confirmed the Sertoli cell-only syndrome. Successful pregnancy and delivery were achieved with microdissection TESE and ICSI. CONCLUSION(S): Paracentric inversion of chromosome 7(q22-31) associated with nonobstructive azoospermia is rare. Chromosome 7q22-31 may be responsible for impaired spermatogenesis.
BACKGROUND: Cardiac memory, electrophysiological remodeling induced by periods of altered ventricular activation, has been observed after resumption of normal activation following ablation of overt accessory pathways. We studied the occurrence and temporal characteristics of cardiac memory (inferior T wave inversions) after ablation of overt posteroseptal accessory pathways. METHODS: T wave changes were assessed in the frontal plane (leads II, aVF, and III) up to one year after the ablation in 125 consecutive patients. T wave polarity immediately after ablation was compared with the pre ablation delta wave polarity and the dominant QRS force in each lead. The number of inferior leads (0-3) with post ablation T wave changes (estimate of degree of cardiac memory) was analyzed in relation to estimates of the degree of preexcitation (accessory pathway refractoriness and QRS duration) prior to ablation. RESULTS: Electrocardiogram (ECG) signs of cardiac memory were present in 123 (98%) of the patients within one day after ablation. The post ablation T wave vector had the same direction as the vector of the pre-excited QRS complex (and delta wave) creating inferior T wave inversions. There was no correlation between the degree of preexcitation pre ablation and the extent of cardiac memory post ablation. A majority (about 90%) of ECGs recorded 3-6 months after the procedure, showed complete or almost complete normalization. CONCLUSIONS: T wave inversions were present in the vast majority of patients, persisted in some patients beyond 3 months, and might be misinterpreted as inferior wall ischemia.
PURPOSE: The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. METHODS AND MATERIALS: Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervals (V5, V10, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. RESULTS: VSB correlated strongly with diarrheal severity at every dose level (p<0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p<or=0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p=0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p=0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V5 and V15. CONCLUSIONS: A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further investigation.
In the standard inverse dynamic method, joint moments are assessed from ground reaction force data and position data, where segmental accelerations are calculated by numerical differentiation of position data after low-pass filtering. This method falls short in analyzing the impact phase, e.g. landing after a jump, by underestimating the contribution of the segmental accelerations to the joint moment assessment. This study tried to improve the inverse dynamics method for the assessment of knee moment by evaluating different cutoff frequencies in low-pass filtering of position data on the calculation of knee moment. Next to this, the effect of an inclusion of direct measurement of segmental acceleration using accelerometers to the inverse dynamics was evaluated. Evidence was obtained that during impact, the contribution of the ground reaction force to the sagittal knee moment was neutralized by the moments generated by very high segmental accelerations. Because the accelerometer-based method did not result in the expected improvement of the knee moment assessment during activities with high impacts, it is proposed to filter the ground reaction force with the same cutoff frequency as the calculated accelerations. When this precaution is not taken, the impact peaks in the moments can be considered as artifacts. On the basis of these findings, we recommend in the search to biomechanical explanations of chronic overuse injuries, like jumper's knee, not to consider the relation with impact peak force and impact peak moment.
Perchloroethylene (PCE) saturations determined from GPR surveys were used as observations for inversion of multiphase flow simulations of a PCE injection experiment (Borden 9 m cell), allowing for the estimation of optimal bulk intrinsic permeability values. The resulting fit statistics and analysis of residuals (observed minus simulated PCE saturations) were used to improve the conceptual model. These improvements included adjustment of the elevation of a permeability contrast, use of the van Genuchten versus Brooks-Corey capillary pressure-saturation curve, and a weighting scheme to account for greater measurement error with larger saturation values. A limitation in determining PCE saturations through one-dimensional GPR modeling is non-uniqueness when multiple GPR parameters are unknown (i.e., permittivity, depth, and gain function). Site knowledge, fixing the gain function, and multiphase flow simulations assisted in evaluating non-unique conceptual models of PCE saturation, where depth and layering were reinterpreted to provide alternate conceptual models. Remaining bias in the residuals is attributed to the violation of assumptions in the one-dimensional GPR interpretation (which assumes flat, infinite, horizontal layering) resulting from multidimensional influences that were not included in the conceptual model. While the limitations and errors in using GPR data as observations for inverse multiphase flow simulations are frustrating and difficult to quantify, simulation results indicate that the error and bias in the PCE saturation values are small enough to still provide reasonable optimal permeability values. The effort to improve model fit and reduce residual bias decreases simulation error even for an inversion based on biased observations and provides insight into alternate GPR data interpretations. Thus, this effort is warranted and provides information on bias in the observation data when this bias is otherwise difficult to assess.
A new adiabatic pulse for population inversion and the principles of its design are presented. The pulse shape is characterized by the combination of two constraints. (i) Adiabatic following of the central isochromat of the spectral region of interest occurs with constant, possibly small adiabaticity parameter; thereby, the center isochromat gets most efficiently inverted. (ii) Frequency and amplitude modulations obey the principle of offset-independent adiabaticity; thus, the inversion dynamics of the center isochromat is extended over the desired bandwidth. Selective population inversion can be achieved rather independently of spatial radio frequency field inhomogeneities and with significantly reduced peak RF amplitude in comparison with the well-known sech/tanh adiabatic pulse.
We present a new approach to the preprocessing of the electroencephalographic time series for EEG inverse solutions. As the first step, EEG recordings are decomposed by multichannel matching pursuit algorithm--in this study we introduce a computationally efficient, suboptimal solution. Then, based upon the parameters of the waveforms fitted to the EEG (frequency, amplitude and duration), we choose those corresponding to the the phenomena of interest, like e.g. sleep spindles. For each structure, the corresponding weights of each channel define a topographic signature, which can be subject to an inverse solution procedure, like e.g. Loreta, used in this work. As an example, we present an automatic detection and parameterization of sleep spindles, appearing in overnight polysomnographic recordings. Inverse solutions obtained for single sleep spindles are coherent with the averages obtained for 20 overnight EEG recordings analyzed in this study, as well as with the results reported previously in literature as inter-subject averages of solutions for spectral integrals, computed on visually selected spindles.
The allele-specific inverse polymerase chain reaction (PCR) technique, which has been explored to detect two linked polymorphic regions simultaneously, was applied to genotype the Se system. The major alleles of the Se system in Japanese are Se, sej defined by a single nucleotide substitution in the Se allele, and se(fus) generated by recombination between the Sec1 and FUT2 genes. The first PCR products using gene-specific primers were self-ligated, and each allele was detected by the second inverse-PCR using allele-specific primers. The 340, 331 and 353-bp products were finally amplified from Se, sej and se(fus) templates, respectively. The first PCR products without mung bean nuclease treatment were not self-ligated and non-specific fragments were amplified in the second PCR, suggesting that non-templated adenylation occurred at the termini during the first PCR. Nuclease digestion of the first PCR products that blunts their termini was found to reduce interference of non-templated adenylation with the intramolecular ligation and to improve the genotyping markedly. This modified allele-specific inverse-PCR method is applicable to analyze haplotypes consisting of separated single nucleotide polymorphisms and recombinant genes.
The purpose of this study is to compare 3 intensity-modulated radiation therapy (IMRT) inverse treatment planning techniques as applied to locally-advanced lung cancer. This study evaluates whether sufficient radiotherapy (RT) dose is given for durable control of tumors while sparing a portion of the esophagus, and whether large number of segments and monitor units are required. We selected 5 cases of locally-advanced lung cancer with large central tumor, abutting the esophagus. To ensure that no more than half of the esophagus circumference at any level received the specified dose limit, it was divided into disk-like sections and dose limits were imposed on each. Two sets of dose objectives were specified for tumor and other critical structures for standard dose RT and for dose escalation RT. Plans were generated using an aperture-based inverse planning (ABIP) technique with the Cimmino algorithm for optimization. Beamlet-based inverse treatment planning was carried out with a commercial simulated annealing package (CORVUS) and with an in-house system that used the Cimmino projection algorithm (CIMM). For 3 of the 5 cases, results met all of the constraints from the 3 techniques for the 2 sets of dose objectives. The CORVUS system without delivery efficiency consideration required the most segments and monitor units. The CIMM system reduced the number while the ABIP techniques showed a further reduction, although for one of the cases, a solution was not readily obtained using the ABIP technique for dose escalation objectives.
The nuclear receptor CAR is a xenobiotic responsive transcription factor that plays a central role in the clearance of drugs and bilirubin while promoting cocaine and acetaminophen toxicity. In addition, CAR has established a "reverse" paradigm of nuclear receptor action where the receptor is active in the absence of ligand and inactive when bound to inverse agonists. We now report the crystal structure of murine CAR bound to the inverse agonist androstenol. Androstenol binds within the ligand binding pocket, but unlike many nuclear receptor ligands, it makes no contacts with helix H12/AF2. The transition from constitutive to basal activity (androstenol bound) appears to be associated with a ligand-induced kink between helices H10 and H11. This disrupts the previously predicted salt bridge that locks H12 in the transcriptionally active conformation. This mechanism of inverse agonism is distinct from traditional nuclear receptor antagonists thereby offering a new approach to receptor modulation.
Source current estimation from MEG measurement is an ill-posed problem that requires prior assumptions about brain activity and an efficient estimation algorithm. In this article, we propose a new hierarchical Bayesian method introducing a hierarchical prior that can effectively incorporate both structural and functional MRI data. In our method, the variance of the source current at each source location is considered an unknown parameter and estimated from the observed MEG data and prior information by using the Variational Bayesian method. The fMRI information can be imposed as prior information on the variance distribution rather than the variance itself so that it gives a soft constraint on the variance. A spatial smoothness constraint, that the neural activity within a few millimeter radius tends to be similar due to the neural connections, can also be implemented as a hierarchical prior. The proposed method provides a unified theory to deal with the following three situations: (1) MEG with no other data, (2) MEG with structural MRI data on cortical surfaces, and (3) MEG with both structural MRI and fMRI data. We investigated the performance of our method and conventional linear inverse methods under these three conditions. Simulation results indicate that our method has better accuracy and spatial resolution than the conventional linear inverse methods under all three conditions. It is also shown that accuracy of our method improves as MRI and fMRI information becomes available. Simulation results demonstrate that our method appropriately resolves the inverse problem even if fMRI data convey inaccurate information, while the Wiener filter method is seriously deteriorated by inaccurate fMRI information.
Spatially characterizing and quantifying the brain electromagnetic response using MEG/EEG data still remains a critical issue since it requires solving an ill-posed inverse problem that does not admit a unique solution. To overcome this lack of uniqueness, inverse methods have to introduce prior information about the solution. Most existing approaches are directly based upon extrinsic anatomical and functional priors and usually attempt at simultaneously localizing and quantifying brain activity. By contrast, this paper deals with a preprocessing tool which aims at better conditioning the source reconstruction process, by relying only upon intrinsic knowledge (a forward model and the MEG/EEG data itself) and focusing on the key issue of localization. Based on a discrete and realistic anatomical description of the cortex, we first define functionally Informed Basis Functions (fIBF) that are subject specific. We then propose a multivariate method which exploits these fIBF to calculate a probability-like coefficient of activation associated with each dipolar source of the model. This estimated distribution of activation coefficients may then be used as an intrinsic functional prior, either by taking these quantities into account in a subsequent inverse method, or by thresholding the set of probabilities in order to reduce the dimension of the solution space. These two ways of constraining the source reconstruction process may naturally be coupled. We successively describe the proposed Multivariate Source Prelocalization (MSP) approach and illustrate its performance on both simulated and real MEG data. Finally, the better conditioning induced by the MSP process in a classical regularization scheme is extensively and quantitatively evaluated.