Citations

Fronto-temporal lobar degeneration (FTLD) is a form of dementia which may manifest through symptoms similar to Alzheimer’s, including language-specific impairment. Linguistic manifestations of the disorder are often described in subjective assessments of the disorder, but not always easily quantifiable using objective tests. This paper investigates a speech characteristic not yet assessed in FTLD patients, that of “temporal cycles” [Henderson et al. (1966); Butterworth and Goldman-Eisler (1979)]. Temporal cycles in the speech of healthy adults consist of alternating and roughly equal periods of fluent and hesitant speech [Roberts and Kirsner (2000)]. A time series analysis of temporal cycles was conducted using spontaneous speech from 45 adults diagnosed with FTLD. Patients’ cognitive functioning was assessed using the language-specific clinical dementia rating (CDR) scale by board-certified neurologists. Periodicity of temporal cycles was quantified using the proportion of the energy in the highest peak to the total energy in the power spectrum. It was found that this measure was correlated with independent CDR assessments. The results of this study indicate that temporal cycles may be used to characterize the effects of neurodegenerative disorders on speech communication. [Work supported by US NIA Grants Nos. R01-AG023195, P50-AG16574, P30-AG19610, and NIH NIA-1R01AG026390, and Univ. of MN Academic Health Center.]

Rapid calculations of the intensity are required for models of the radiation force generated by linear ultrasound phased arrays. To determine the computation times and numerical errors produced by two medical ultrasound simulation packages, namely, FIELD II and FOCUS, comparisons of the calculated pressures and intensities are performed using a simulated Vermon L5 phased array probe with 128 active elements. In these simulations, the array generates a fixed focus 25 mm from the array for a 5-MHz excitation, and the pressure field is computed on a 133 × 133 × 261 rectilinear grid that is centered at the focus. Half wavelength sampling is employed in all three directions. In FIELD II, this calculation takes approximately 4 h on a 64-bit laptop running Linux, and in FOCUS, the same calculation takes less than 4 min on the same computer. The numerical errors are also much smaller with FOCUS. Details of the simulation approaches employed for this transducer model will be presented, including selection of FIELD II and FOCUS simulation parameters and calculations of the reference pressure field for error evaluations. The impact of numerical errors on shear wave calculations will also be discussed.

Vibro-acoustography is an ultrasound-based imaging modality that maps the acoustic response of an object induced by acoustic radiation force. The method employs two ultrasound beams with frequencies separated by a small difference, typically in the kilohertz range. Using a 1.75D array transducer, which has multiple rows of elements, offers an advantage over linear array transducers because it allows for focusing in the elevation direction. We have performed simulations of different arrangements for the apertures assigned to the two ultrasound frequencies and evaluated resolution and sidelobe levels for different arrangements. However, the large size of the elements produces grating lobes in the transmitted fields. We will describe metrics for evaluating grating lobe levels compared to the main lobe of the transmitted field as a quantitative approach to optimize aperture design. We present experimental measurements of the transmitted field and compare with simulation results. Finally, we present imaging results from phantom experiments. This beamforming study is directed toward improving vibro-acoustography image formation using a General Electric Vivid 7 scanner for breast and thyroid imaging. [Mayo Clinic and two of the authors have potential financial interest related to devices or technology referenced above. Work supported by NIH Grant No. R21CA121579 and AIUM Award No. AIUM-EER#1.]

Multiple methods have been proposed to characterize the viscoelastic material properties of soft tissues to differentiate normal from pathological tissue. Shearwave dispersion ultrasound vibrometry is a method that uses the dispersion of the shear wave velocity to characterize tissue shear elasticity and viscosity. It has recently been shown [M. W. Urban and J. F. Greenleaf, Phys. Med. Biol. 54, 5919–5933 (2009)] that the Kramers–Kronig relationships can be applied to shear wave measurements in ex vivo skeletal muscle over a frequency bandwidth of 100–600 Hz. We will describe this process where shear wave attenuation is modeled using a power law, and the shear wave velocity dispersion is predicted by applying the Kramers–Kronig relationships. In this study, we apply this method to shear wave propagation measurements made in different soft tissues such as ex vivo porcine skeletal muscle and kidney and in vivo porcine liver. The shear wave velocity predictions using the Kramers–Kronig relationships agree with the velocity measurements. The mean square error for these tissues ranged from 0.0024–0.0625 m2/s2. The Kramers–Kronig relationships can be used in shear wave propagation measurements in different types of soft tissues. [This work was supported in part by NIH Grants Nos. EB002167 and DK082408.]

Dynamic radiation force has been used in several types of applications, and is performed by modulating ultrasound with different methods. By modulating ultrasound, energy can be transmitted to tissue, in this case a dynamic force to elicit a low frequency cyclic displacement to inspect the material properties of the tissue. In this paper, different types of modulation are explored including amplitude modulation (AM), double sideband suppressed carrier amplitude modulation AM, linear frequency modulation, and frequency-shift keying. Generalized theory is presented for computing the radiation force through the short-term time average of the energy density for these various types of modulation. Examples of modulation with different types of signals including sine waves, square waves, and triangle waves are shown. Using different modulating signals, multifrequency radiation force with different numbers of frequency components can be created, and can be used to characterize tissue mimicking materials and soft tissue. Results for characterization of gelatin phantoms using a method of vibrating an embedded sphere are presented. Different degrees of accuracy were achieved using different modulation techniques and modulating signals. Modulating ultrasound is a very flexible technique to produce radiation force with multiple frequency components that can be used for various applications.

The high prevalence of no-shows in residents’ primary care clinic acts as a barrier to continuity of care, results in loss of outpatient learning opportunities, and may result in more emergency department (ED) visits. The authors seek to identify if high rates of no-shows correlate with more ED visits. In a selected primary care internal medicine (PCIM) continuity clinic, 650 patients were randomly selected, with 325 patients each from the faculty and resident practices. The number of ED visits between January 1, 2006, and December 30, 2008, was recorded. Demographic characteristics of the population were obtained, and comparisons between the faculty and resident groups were performed using Student t test. Linear multiple regression analysis was performed to compare frequency of ED visits between the faculty and the resident groups, controlling for age, interpreter requirement, number of ED visits, proportion of no-shows, and insurance type. A P value <.05 was considered statistically significant. During 2006-2008, the average number of ED visits per patient in the faculty’s practice was 2.1 compared with 4.1 in the resident’s practice ( P < .001). A multiple linear regression model showed that patients who had more ED visits were likely to be younger ( P = .004), had shorter duration of care in the PCIM clinic ( P < .001), and had a higher proportion of no-shows to the PCIM clinic ( P < .001). There was no statistical difference between faculty and resident practice after adjusting for the above-mentioned variables. Shorter duration in the PCIM clinic and higher proportion of missed appointments were associated with more ED visits, but the use of interpreters and Medicaid insurance did not result in more ED visits. Future interventions are necessary to reduce the no-show rate in the clinic as this may result in a reduction of ED visits.

A collaborative care model (CCM) has been implemented for management of depression. This paper studies the impact that the CCM had on cost measures for the period of six months after initial diagnosis of depression compared to patients receiving usual care (UC). There was a significant increase in the CPT costs for the six months following diagnosis in the CCM group ($451.35 vs. $323.50, P < 0.001). The average CPT cost rank and CPT cost differential were also significantly increased in the CCM group. The adjusted means of the CPT costs were (when controlling for prior utilization) $452.11 for the CCM group and $322.09 for UC (P < 0.001). In the CCM group; there were 161 patients (73.5%) that achieved a clinical response for their depression compared to the UC group, which had a 15.1% (18/119) response rate (P < 0.001). There also was a significant difference between the groups in those who were symptoms free of their depression (PHQ-9 score < 5), with the CCM having 59.4% of the patients symptom-free compared to 10.9% of the UC group (P < 0.001). In this group of patients, CCM is associated with markedly improved clinical outcomes for depression, however with a modest short-term increase in CPT costs.

ABSTRACTStaphylococcal enterotoxin B (SEB), a shock-inducing exotoxin synthesized byStaphylococcus aureus, is an important cause of food poisoning and is a class B bioterrorism agent. SEB mediates antigen-independent activation of a major subset of the T-cell population by cross-linking T-cell receptors (TCRs) with class II major histocompatibility complex (MHC-II) molecules of antigen-presenting cells, resulting in the induction of antigen independent proliferation and cytokine secretion by a significant fraction of the T-cell population. Neutralizing antibodies inhibit SEB-mediated T-cell activation by blocking the toxin's interaction with the TCR or MHC-II and provide protection against the debilitating effects of this superantigen. We derived and searched a set of monoclonal mouse anti-SEB antibodies to identify neutralizing anti-SEB antibodies that bind to different sites on the toxin. A pair of non-cross-reactive, neutralizing anti-SEB monoclonal antibodies (MAbs) was found, and a combination of these antibodies inhibited SEB-induced T-cell proliferation in a synergistic rather than merely additive manner. In order to engineer antibodies more suitable than mouse MAbs for use in humans, the genes encoding the VL and VH gene segments of a synergistically acting pair of mouse MAbs were grafted, respectively, onto genes encoding the constant regions of human Igκ and human IgG1, transfected into mammalian cells, and used to generate chimeric versions of these antibodies that had affinity and neutralization profiles essentially identical to their mouse counterparts. When tested in cultures of human peripheral blood mononuclear cells or splenocytes derived from HLA-DR3 transgenic mice, the chimeric human-mouse antibodies synergistically neutralized SEB-induced T-cell activation and cytokine production.

Background— Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that occurs in previously healthy women. We identified prolactin, mainly its 16-kDa angiostatic and proapoptotic form, as a key factor in PPCM pathophysiology. Previous reports suggest that bromocriptine may have beneficial effects in women with acute onset of PPCM. Methods and Results— A prospective, single-center, randomized, open-label, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard care (PPCM-Std; n=10) versus standard care plus bromocriptine for 8 weeks (PPCM-Br, n=10) was conducted. Because mothers receiving bromocriptine could not breast-feed, the 6-month outcome of their children (n=21) was studied as a secondary end point. Blinded clinical, hemodynamic, and echocardiographic assessments were performed at baseline and 6 months after diagnosis. Cardiac magnetic resonance imaging was performed 4 to 6 weeks after diagnosis in PPCM-Br patients. There were no significant differences in baseline characteristics, including serum 16-kDa prolactin levels and cathepsin D activity, between the 2 study groups. PPCM-Br patients displayed greater recovery of left ventricular ejection fraction (27% to 58%; P =0.012) compared with PPCM-Std patients (27% to 36%) at 6 months. One patient in the PPCM-Br group died compared with 4 patients in the PPCM-Std group. Significantly fewer PPCM-Br patients (n=1, 10%) experienced the composite end point of poor outcome defined as death, New York Heart Association functional class III/IV, or left ventricular ejection fraction <35% at 6 months compared with the PPCM-Std patients (n=8, 80%; P =0.006). Cardiac magnetic resonance imaging revealed no intracavitary thrombi. Infants of mothers in both groups showed normal growth and survival. Conclusions— In this trial, the addition of bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM, although the number of patients studied was small and the results cannot be considered definitive. Larger-scale multicenter and blinded studies are in progress to test this strategy more robustly.