Neoadjuvant Use of Photodynamic Therapy in Basal Cell and Squamous Cell Carcinomas of the Face

Background. This preliminary study sought to determine the success of photodynamic therapy (PDT) in reducing lesion size in an effort to assess the potential application of this treatment approach in a neoadjuvant role. Objectives. To quantify the effects of PDT on lesion area (mm2) for basal cell and squamous cell carcinomas of the face. Results. Eighteen participants (10 BCC lesions and 8 SCC lesions of the face) were assessed. Four lesions (all from the BCC group) showed a complete response to PDT. Of the remaining 14 lesions, 85.7% (n = 12) showed reductions in lesion area, while two lesions showed increase in lesion area. Proportional reductions for the 12 lesions that did not demonstrate complete response or an increase in area following-PDT were found to range from 13.2% to 85.1% (BCC) and 6.7% to 89.7% (SCC). Conclusions. PDT as a neoadjuvant treatment may provide a simple, efficient, and viable approach to reducing the area of malignant lesions of the face with the advantage of reduced cosmetic and aesthetic morbidities

An auditory-perceptual and pupillometric study of vocal strain and listening effort in adductor spasmodic dysphonia

© 2020 by the authors. This study evaluated ratings of vocal strain and perceived listening effort by normal hearing participants while listening to speech samples produced by talkers with adductor spasmodic dysphonia (AdSD). In addition, objective listening effort was measured through concurrent pupillometry to determine whether listening to disordered voices changed arousal as a result of emotional state or cognitive load. Recordings of the second sentence of the Rainbow Passage produced by talkers with varying degrees of AdSD served as speech stimuli. Twenty naïve young adult listeners perceptually evaluated these stimuli on the dimensions of vocal strain and listening effort using two separate visual analogue scales. While making the auditory-perceptual judgments, listeners\u27 pupil characteristics were objectively measured in synchrony with the presentation of each voice stimulus. Data analyses revealed moderate-to-high inter- and intra-rater reliability. A significant positive correlation was found between the ratings of vocal strain and listening effort. In addition, listeners displayed greater peak pupil dilation (PPD) when listening to more strained and effortful voice samples. Findings from this study suggest that when combined with an auditory-perceptual task, non-volitional physiologic changes in pupil response may serve as an indicator of listening and cognitive effort or arousal

Characteristics of velopharyngeal dysfunction in 22q11.2 deletion syndrome: A retrospective case-control study

Objective: To identify and describe the dynamic features of velopharyngeal dysfunction (VPD) in patients with 22q11.2 deletion syndrome relative to patients with non-syndromic cleft palates. Study design: Retrospective case-control study. Setting: Pediatric tertiary care center. Subjects and methods: A total of 30 children (aged 9-16 years) with VPD were included in this study. Fifteen children with a definitive diagnosis of 22q11.2 deletion syndrome requiring surgical VPD repair were included in the 22q11.2 deletion syndrome group. Fifteen age-and sex-matched children with non-syndromic cleft palate requiring surgical VPD repair were included in the non-syndromic cleft palate group for comparison. Velar displacement, lateral pharyngeal wall displacement, and lateral pharyngeal wall motion pattern data were extracted from preoperative Multiview Videofluoroscopy imaging studies of all children and compared across groups. Results: Lateral pharyngeal wall displacement was found to be reduced in the 22q11.2 deletion syndrome group (U = 29.50, p =.001, r =.63). However, measures of velar displacement were not observed to differ between groups. Similarly, lateral pharyngeal wall motion pattern distributions were not found to differ across these two groups. Conclusions: Velopharyngeal dysfunction in patients with 22q11.2 deletion syndrome showed differences in dynamic velopharyngeal function when compared to non-syndromic cleft palate patients. The current findings provide initial insights into the unique aspects of velopharyngeal dysfunction for patients with 22q11.2 deletion syndrome. These findings may guide further efforts directed toward understanding the dynamic velopharyngeal characteristics of this population and potentially optimize surgical management and functional outcomes

How Consistent Is Competent? Examining Variance in Psychomotor Skills Assessment

Purpose Direct assessment of trainee performance across time is a core tenet of competency-based medical education. Unlike variability of psychomotor skills across levels of expertise, performance variability exhibited by a particular trainee across time remains unexplored. The goal of this study was to document the consistency of individual surgeons\u27 technical skill performance. Method A secondary analysis of assessment data (collected in 2010-2012, originally published in 2015) generated by a prospective cohort of participants at Montreal Children\u27s Hospital with differing levels of expertise was conducted in 2017. Trained raters scored blinded recordings of a myringotomy and tube insertion performed 4 times by junior and senior residents and attending surgeons over a 6-month period using a previously reported assessment tool. Descriptive exploratory analyses and univariate comparison of standard deviations (SDs) were conducted to document variability within individuals across time and across training levels. Results Thirty-six assessments from 9 participants were analyzed. The SD of scores for junior residents was highly variable (5.8 out of a scale of 30 compared with 1.8 for both senior residents and attendings [F(2,19) = 5.68, P \u3c 0.05]). For a given individual, the range of scores was twice as large for junior residents than for senior residents and attendings. Conclusions Surgical residents may display highly variable performances across time, and individual variability appears to decrease with increasing expertise. Operative skill variability could be underrepresented in direct observation assessment; emphasis on an adequate amount of repetitive evaluations for junior residents may be needed to support judgments of competence or entrustment

Reflective practice in speech-language pathology: relevance for practice and education = La pratique réflexive en orthophonie : pertinence pour la pratique et l’enseignement

As a profession, speech-language pathology appears to have become interested in reflection and reflective practice as important components of clinical practice and education. However, little systematic consideration of the potential value of reflective practice within the field has been undertaken. The purpose of this paper seeks to consider how reflective practice is relevant to contemporary speech-language pathology practice. Drawing on comprehensive and diverse theoretical literature, we suggest that reflective practice is a framework worthy of consideration because of its potential to: (1) foster the generation of knowledge from practice, (2) balance and contextualize science with patient care, (3) facilitate the integration of theory and practice, (4) link evidence-based practice with clinical expertise, and finally, (5) contribute to the cultivation of ethical practice. © 2016, Canadian Association of Speech-Language Pathologists and Audiologists. All Rights Reserved

A novel protamine variant reversal of heparin anticoagulation in human blood in vitro

AbstractPurpose: Protamine reversal of heparin anticoagulation during cardiovascular surgery may cause severe hypotension and pulmonary hypertension. A novel protamine variant, [+18RGD], has been developed that effectively reverses heparin anticoagulation without toxicity in canine experiments. Heretofore, human studies have not been undertaken. This investigation hypothesized that [+18RGD] would effectively reverse heparin anticoagulation of human blood in vitro. Methods: Fifty patients who underwent anticoagulation therapy during vascular surgery had blood sampled at baseline and 30 minutes after receiving heparin (150 IU/kg). Activated clotting times were used to define specific quantities of [+18RGD] or protamine necessary to completely reverse heparin anticoagulation in the blood sample of each patient. These defined amounts of [+18RGD] or protamine were then administered to the heparinized blood samples, and percent reversals of activated partial thromboplastin time, thrombin clotting time, and antifactor Xa/IIa levels were determined. In addition, platelet aggregation assays, as well as platelet and white blood cell counts were performed. Results: [+18RGD] and protamine were equivalent in reversing heparin as assessed by thrombin clotting time, antifactor Xa, antifactor IIa levels, and white blood cell changes. [+18RGD], when compared with protamine, was superior in this regard, as assessed by activated partial thromboplastin time (94.5 ± 1.0 vs 86.5 ± 1.3%δ, respectively; p < 0.001) and platelet declines (–3.9 ± 2.9 vs –12.8 ± 3.4 per mm3, respectively; p = 0.048). Platelet aggregation was also decreased for [+18RGD] compared with protamine (23.6 ± 1.5 vs 28.5 ± 1.9%, respectively; p = 0.048). Conclusions: [+18RGD] was as effective as protamine for in vitro reversal of heparin anticoagulation by most coagulation assays, was statistically more effective at reversal than protamine by aPTT assay, and was associated with lesser platelet reductions than protamine. [+18RGD], if less toxic than protamine in human beings, would allow for effective clinical reversal of heparin anticoagulation. (J Vasc Surg 1997;26:1043-8.

Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheumatoid arthritis: results of an analysis of the literature over the past 16 years

Objective To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNF alpha) inhibitors in rheumatoid arthritis (RA) patients. Methods A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNF alpha inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifiable enrolment start date. Results 44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identified as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no significant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a significant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modified Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, significant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modified Sharp score. Conclusion Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNF alpha inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials.Pathophysiology and treatment of rheumatic disease

Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data

New transiting planet candidates are identified in sixteen months (May 2009 - September 2010) of data from the Kepler spacecraft. Nearly five thousand periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1,091 viable new planet candidates, bringing the total count up to over 2,300. Improved vetting metrics are employed, contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multi-quarter photo-center offsets derived from difference image analysis which identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the new candidates. Ephemerides (transit epoch, T_0, and orbital period, P) are tabulated as well as the products of light curve modeling: reduced radius (Rp/R*), reduced semi-major axis (d/R*), and impact parameter (b). The largest fractional increases are seen for the smallest planet candidates (197% for candidates smaller than 2Re compared to 52% for candidates larger than 2Re) and those at longer orbital periods (123% for candidates outside of 50-day orbits versus 85% for candidates inside of 50-day orbits). The gains are larger than expected from increasing the observing window from thirteen months (Quarter 1-- Quarter 5) to sixteen months (Quarter 1 -- Quarter 6). This demonstrates the benefit of continued development of pipeline analysis software. The fraction of all host stars with multiple candidates has grown from 17% to 20%, and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the Habitable Zone are forthcoming if, indeed, such planets are abundant.Comment: Submitted to ApJS. Machine-readable tables are available at http://kepler.nasa.gov, http://archive.stsci.edu/kepler/results.html, and the NASA Exoplanet Archiv

MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically

Dissociation of virtual photons in events with a leading proton at HERA

The ZEUS detector has been used to study dissociation of virtual photons in events with a leading proton, gamma^* p -> X p, in e^+p collisions at HERA. The data cover photon virtualities in two ranges, 0.03<Q^2<0.60 GeV^2 and 2<Q^2<100 GeV^2, with M_X>1.5 GeV, where M_X is the mass of the hadronic final state, X. Events were required to have a leading proton, detected in the ZEUS leading proton spectrometer, carrying at least 90% of the incoming proton energy. The cross section is presented as a function of t, the squared four-momentum transfer at the proton vertex, Phi, the azimuthal angle between the positron scattering plane and the proton scattering plane, and Q^2. The data are presented in terms of the diffractive structure function, F_2^D(3). A next-to-leading-order QCD fit to the higher-Q^2 data set and to previously published diffractive charm production data is presented