Effects of cochlear implantation on binaural hearing in adults with unilateral hearing loss

A FDA clinical trial was carried out to evaluate the potential benefit of cochlear implant (CI) use for adults with unilateral moderate-to-profound sensorineural hearing loss. Subjects were 20 adults with moderate-to-profound unilateral sensorineural hearing loss and normal or near-normal hearing on the other side. A MED-EL standard electrode was implanted in the impaired ear. Outcome measures included: (a) sound localization on the horizontal plane (11 positions, −90° to 90°), (b) word recognition in quiet with the CI alone, and (c) masked sentence recognition with the target at 0° and the masker at −90°, 0°, or 90°. This battery was completed preoperatively and at 1, 3, 6, 9, and 12 months after CI activation. Normative data were also collected for 20 age-matched control subjects with normal or near-normal hearing bilaterally. The CI improved localization accuracy and reduced side bias. Word recognition with the CI alone was similar to performance of traditional CI recipients. The CI improved masked sentence recognition when the masker was presented from the front or from the side of normal or near-normal hearing. The binaural benefits observed with the CI increased between the 1- and 3-month intervals but appeared stable thereafter. In contrast to previous reports on localization and speech perception in patients with unilateral sensorineural hearing loss, CI benefits were consistently observed across individual subjects, and performance was at asymptote by the 3-month test interval. Cochlear implant settings, consistent CI use, and short duration of deafness could play a role in this result

Comparison of two cochlear implant coding strategies on speech perception

OBJECTIVE: Assess whether differences in speech perception are observed after exclusive listening experience with high-definition continuous interleaved sampling (HDCIS) versus fine structure processing (FSP) coding strategies. METHODS: Subjects were randomly assigned at initial activation of the external speech processor to receive the HDCIS or FSP coding strategy. Frequency filter assignments were consistent across subjects. The speech perception test battery included CNC words in quiet, HINT sentences in quiet and steady noise (+10 dB SNR), AzBio sentences in quiet and a 10-talker babble (+10 dB SNR), and BKB-SIN. Assessment intervals included 1, 3, and 6 months post-activation. RESULTS: Data from 22 subjects (11 with HDCIS and 11 with FSP) were assessed over time. Speech perception performance was not significantly different between groups. DISCUSSION: Speech perception performance was not significantly different after 6 months of listening experience with the HDCIS or FSP coding strategy

Induction of effective and antigen-specific antitumour immunity by a liposomal ErbB2/HER2 peptide-based vaccination construct

Efficient delivery of tumour-associated antigens to appropriate cellular compartments of antigen-presenting cells is of prime importance for the induction of potent, cell-mediated antitumour immune responses. We have designed novel multivalent liposomal constructs that co-deliver the p63–71 cytotoxic T Lymphocyte epitope derived from human ErbB2 (HER2), and HA307–319, a T-helper (Th) epitope derived from influenza haemagglutinin. Both peptides were conjugated to the surface of liposomes via a Pam3CSS anchor, a synthetic lipopeptide with potent adjuvant activity. In a murine model system, vaccination with these constructs completely protected BALB/c mice from subsequent s.c. challenge with ErbB2-expressing, but not ErbB2-negative, murine renal carcinoma (Renca) cells, indicating the induction of potent, antigen-specific immune responses. I.v. re-challenge of tumour-free animals 2 months after the first tumour cell inoculation did not result in the formation of lung tumour nodules, suggesting that long-lasting, systemic immunity had been induced. While still protecting the majority of vaccinated mice, a liposomal construct lacking the Th epitope was less effective than the diepitope construct, also correlating with a lower number of CD8+ IFN-γ+ T-cells identified upon ex vivo peptide restimulation of splenocytes from vaccinated animals. Importantly, in a therapeutic setting treatment with the liposomal vaccines resulted in cures in the majority of tumour-bearing mice and delayed tumour growth in the remaining ones. Our results demonstrate that liposomal constructs which combine Tc and Th peptide antigens and lipopeptide adjuvants can induce efficient, antigen-specific antitumour immunity, and represent promising synthetic delivery systems for the design of specific antitumour vaccines

MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape

Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove. The common escape mutant TSNLQEQIGW bound HLA-B*57:01 canonically, adopting a dramatically different conformation than the TW10 peptide. This affected recognition by killer cell immunoglobulin-like receptor (KIR) 3DL1 expressed on NK cells. We thus define a previously uncharacterized feature of the human leukocyte antigen class I (HLA-I) immunopeptidome that has implications for viral immune escape. We further suggest that recognition of the HLA-B*57:01-TW10 epitope is governed by a 'molecular tension' between the adaptive and innate immune systems

Nonverbal synchrony as a marker of alliance ruptures

Findings from the past 5 decades of empirical research on the working alliance suggest its importance in psychotherapy. Recent studies have sought to identify markers of the alliance, of which one of the most promising candidates is nonverbal synchrony. Delving into processes that constitute the alliance, such as alliance ruptures, may shed light on underlying mechanisms of the association between nonverbal synchrony and the therapeutic relationship. The present study examines whether nonverbal synchrony can serve as a marker of alliance ruptures. To achieve this aim, 418 sessions of 75 therapeutic dyads were coded for ruptures, using the Rupture Resolution Rating System, and for nonverbal synchrony, using motion energy analysis. A mixed-method analysis, integrating multilevel nested models with a case study analysis, was implemented. The results of the multilevel nested models suggest that nonverbal synchrony is significantly associated with confrontational ruptures, whereas withdrawal ruptures showed no such association. The findings of the case analysis suggest that moments of especially high nonverbal synchrony during a rupture are those in which the therapist made great efforts to be attentive to the patient when the patient acted in a confrontational manner. The findings of the present study demonstrate the potential of nonverbal synchrony to serve as a marker of confrontational ruptures. The findings support the social glue assumption, according to which therapists may seek higher levels of nonverbal synchrony with patients to maintain a strong alliance in the face of difficulties

Shedding light on the effects of supportive techniques on nonverbal synchrony and their moderators in psychotherapy for depression

Objective: Accumulating research demonstrates the importance of utilizing supportive techniques in psychotherapy; however, little is known about therapeutic processes that are set in motion following the use of supportive techniques. The present study examined the effects of supportive techniques on nonverbal synchrony, both at the sample level and at the individual differences level. Method: The sample consisted of 86 patients from a randomized controlled trial for treatment of depression. Supportive techniques were rated by patients and therapists after every session, and nonverbal synchrony was quantified by motion energy analysis (MEA) for each session. The ability of supportive techniques to predict subsequent nonverbal synchrony was examined using polynomial regression and response surface analysis. Results: The findings suggest that, at the sample level, greater use of supportive techniques was a significant predictor of subsequent higher levels of nonverbal synchrony. At the individual differences level, this effect was significant for patients with low levels of depression severity and personality disorders, yet not significant for patients with high levels. Conclusion: The present study demonstrates that greater use of supportive techniques in treatment may facilitate a process that manifests as higher levels of synchrony, especially for patients with lower levels of personality disorders and depression