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Purpose The impact of clear speech, increased vocal intensity, and rate reduction on acoustic characteristics of vowels was compared in speakers with Parkinson’s disease (PD), speakers with multiple sclerosis (MS), and healthy controls. Method Speakers read sentences in habitual, clear, loud, and slow conditions. Variations in clarity, intensity, and rate were stimulated using magnitude production. Formant frequency values for peripheral and nonperipheral vowels were obtained at 20%, 50%, and 80% of vowel duration to derive static and dynamic acoustic measures. Intensity and duration measures were obtained. Results Rate was maximally reduced in the slow condition, and vocal intensity was maximized in the loud condition. The clear condition also yielded a reduced articulatory rate and increased intensity, although less than for the slow or loud conditions. Overall, the clear condition had the most consistent impact on vowel spectral characteristics. Spectral and temporal distinctiveness for peripheral–nonperipheral vowel pairs was largely similar across conditions. Conclusions Clear speech maximized peripheral and nonperipheral vowel space areas for speakers with PD and MS while also reducing rate and increasing vocal intensity. These results suggest that a speech style focused on increasing articulatory amplitude yields the most robust changes in vowel segmental articulation.

Purpose This study investigated how different instructions for eliciting clear speech affected selected acoustic measures of speech. Method Twelve speakers were audio-recorded reading 18 different sentences from the Assessment of Intelligibility of Dysarthric Speech (Yorkston & Beukelman, 1984). Sentences were produced in habitual, clear, hearing impaired, and overenunciate conditions. A variety of acoustic measures were obtained. Results Relative to habitual, the clear, hearing impaired, and overenunciate conditions were associated with different magnitudes of acoustic change for measures of vowel production, speech timing, and vocal intensity. The overenunciate condition tended to yield the greatest magnitude of change in vowel spectral measures and speech timing, followed by the hearing impaired and clear conditions. SPL tended to be the greatest in the hearing impaired condition for half of the speakers studied. Conclusions Different instructions for eliciting clear speech yielded acoustic adjustments of varying magnitude. Results have implications for direct comparison of studies using different instructions for eliciting clear speech. Results also have implications for optimizing clear speech training programs.

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers’ discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

The development of vaccines against specific types of cancers will offer new modalities for therapeutic intervention. Here we describe the synthesis of a novel vaccine construction prepared from spherical gold nanoparticles of 3–5 nm core diameters. The particles were coated with both the tumor-associated glycopeptides antigens containing the cell-surface mucin MUC4 with Thomsen Friedenreich (TF) antigen attached at different sites and a 28-residue peptide from the complement derived protein C3d to act as a B-cell activating “molecular adjuvant”. The synthesis entailed solid phase glycopeptide synthesis, design of appropriate linkers and attachment chemistry of the various molecules to the particles. Attachment to the gold surface was mediated by a novel thiol-containing 33 atom linker which was further modified to be included as a third “spacer” component in the synthesis of several three-component vaccine platforms. Groups of mice were vaccinated either with one of the nanoplatform constructs or with control particles without antigen coating. Evaluation of sera from the immunized animals in enzyme immunoassays (EIA) against each glycopeptide antigen showed a small but statistically significant immune response with production of both IgM and IgG isotypes. Vaccines with one carbohydrate antigen (B, C and E) gave more robust responses than the one with two contiguous disaccharides (D), and vaccine E with a TF antigen attached to threonine at the 10th position of the peptide was selected for IgG over IgM suggesting isotype switching. The data suggested that this platform may be a viable delivery system for tumor-associated glycopeptide antigens.

Summary Lenalidomide has demonstrated impressive antileukaemic effects in patients with chronic lymphocytic leukaemia (CLL). The mechanism(s) by which it mediates these effects remain unclear. Clinically, CLL patients treated with lenalidomide demonstrate an acute inflammatory reaction, the tumour flare reaction that is suggestive of an immune activation phenomenon. Samples from CLL patients treated with lenalidomide were used to evaluate its effect on the tumour cell and components of its microenvironment (immune cellular and cytokine). Lenalidomide was unable to directly induce apoptosis in CLL cells in vitro, however it modulated costimulatory (CD80, CD83, CD86) surface molecules on CLL cells in vitro and in vivo. Concurrently, we demonstrated that NK cell proliferation was induced by lenalidomide treatment in patients and correlated with clinical response. Cytokine analysis showed increase in levels of TNF-α post-lenalidomide treatment, consistent with acute inflammatory reaction. Furthermore, the basal cytokine profile (high IL-8, MIG, IP-10 and IL-4 levels and low IL-5, MIP1a, MIP1b, IL12/p70) was predictive of clinical response to lenalidomide. Collectively, our correlative studies provide further evidence that the antileukaemic effect of lenalidomide in CLL is mediated not only through modulation of the leukaemic clone but also through elements of the tumour microenvironment.

Positive surgical margin rates at robot assisted radical cystectomy for advanced bladder cancer were similar to those in open cystectomy series in a large, multi-institutional, prospective cohort. Sequential case number, a surrogate for the learning curve and institutional volume were not significantly associated with positive margins at robot assisted radical cystectomy.

Objectives:To develop and test the effectiveness of an Internet-based self management program by multidisciplinary health care professionals for patients with heart failure (HF).Methods:The comprehensive educational material for HF was created and posted on a website. A computer with Internet connection and computer training were provided first. A secure and simple web-based recording system of vital signs and health behaviors and a mechanism for feedback regarding each participant’s record were developed. A randomized controlled trial with a one-year intervention was conducted using a total of 40 patients who were assessed three times in their homes. An intention-to-treat analysis used multivariate statistics.Results:The treatment group had a high (85%) adherence to the intervention. Only the treatment group showed a significant improvement in the knowledge level (p < 0.001), amount of exercise (p = 0.001), and quality of life (p = 0.001), and reduction in HF related symptoms (dyspnea, p = 0.001; fatigue, p = 0.003; functional emotion, p < 0.001), blood pressure (systolic, p = 0.002; diastolic, p < 0.001), frequency of emergency room visit, and length of hospital stay (both p = 0.001).Conclusions:An effective program to change one’s behaviors in managing HF takes a multidisciplinary approach to create and provide feedback regarding a patient’s daily record, which can be accomplished through Internet use.