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Summary Objective Singers undergoing tonsillectomy are understandably concerned about possible sequelae to their voice. The surgical risks of laryngeal damage from intubation and upper airway scarring are valid reasons for singers to carefully consider their options for treatment of tonsil-related symptoms. No prior studies have statistically assessed objective voice outcomes in a group of adult singers undergoing tonsillectomy. This study determined the impact of tonsillectomy on the adult singing voice by determining if there were statistically significant changes in preoperative versus postoperative acoustic, aerodynamic, and Voice-Related Quality of Life (VRQOL) measures. Study Design Prospective cohort study. Setting Tertiary Referral Academic Hospital Subjects Thirty singers undergoing tonsillectomy from 2012 to 2019. Methods Acoustic recordings were obtained with Computerized Speech Lab (CSL) (Pentax CSL 4500) and analyzed with the Multidimensional Voice Program (MDVP) (Pentax MDVP) and Pratt Acoustic Analysis Software. Estimates of aerodynamic vocal efficiency were obtained and analyzed using the Phonatory Aerodynamic System (Pentax PAS 6600). Preoperative VRQOL scores were recorded, and singers were instructed to refrain from singing for 3 weeks following tonsillectomy. Repeat acoustic and aerodynamic measures as well as VRQOL scores were obtained at the first postoperative visit. Results Average postoperative acoustic (jitter, shimmer, HNR) and aerodynamic (sound pressure level divided by subglottal pressure) parameters related to laryngeal phonatory function did not differ significantly from preoperative measures. The only statistically significant change in postoperative measures of resonance was a decrease in the 3rd formant (F3) for the /a/ vowel. Average postoperative VRQOL scores (79.8, SD18.7) improved significantly from preoperative VRQOL scores (89, SD12.2) (P = 0.007). Conclusions Tonsillectomy does not appear to alter laryngeal voice production in adult singers as measured by standard acoustic and aerodynamic parameters. The observed decrease in F3 for the /a/ vowel is hypothetically related to increasing the pharyngeal cross-sectional area by removing tonsillar tissue, but this would not be expected to appreciably impact the perceptual characteristics of the vowel. Singers’ self-assessment (VRQOL) improved after tonsillectomy.

Purpose The purpose of this study was to obtain a more comprehensive understanding of the pathophysiology and impact on daily voice use of nonphonotraumatic vocal hyperfunction (NPVH). Method An ambulatory voice monitor collected 1 week of data from 36 patients with NPVH and 36 vocally healthy matched controls. A subset of 11 patients with NPVH were monitored after voice therapy. Daily voice use measures included neck-skin acceleration magnitude, fundamental frequency ( f o ), cepstral peak prominence (CPP), and the difference between the first and second harmonic magnitudes (H1–H2). Additional comparisons included 118 patients with phonotraumatic vocal hyperfunction (PVH) and 89 additional vocally healthy controls. Results The NPVH group, compared to the matched control group, exhibited increased f o (Cohen's d = 0.6), reduced CPP ( d = −0.9), and less positive H1–H2 skewness ( d = −1.1). Classifiers used CPP mean and H1–H2 mode to maximally differentiate the NPVH and matched control groups (area under the receiver operating characteristic curve of 0.78). Classifiers performed well on unseen data: the logit decreased in patients with NPVH after therapy; ≥ 85% of the control and PVH groups were identified as “normal” or “not NPVH,” respectively. Conclusions The NPVH group's daily voice use is less periodic (CPP), is higher pitched ( f o ), and has less abrupt vocal fold closure (H1–H2 skew) compared to the matched control group. The combination of CPP mean and H1–H2 mode appears to reflect a pathophysiological continuum in NPVH patients of inefficient phonation with minimal potential for phonotrauma. Further validation of the classification model is needed to better understand potential clinical uses. Supplemental Material https://doi.org/10.23641/asha.14390771

Objectives Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV‐1 infection (PHI). Four‐drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four‐drug regimens used in the Research in Viral Eradication of HIV‐1 Reservoirs (RIVER) study. Methods At enrolment, ART‐naïve adult participants or those newly commenced on ART were initiated or intensified to four‐drug regimens within 4 weeks of PHI. Rapid start was defined as pre‐confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient‐reported adherence measured by 7‐day recall and regimen switches between enrolment and randomization, respectively. Results Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV‐1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV‐1. Twenty (37%) started a four‐drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load

Plasmodium falciparum merozoite surface protein (PfMSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant PfMSP2 (rPfMSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic PfMSP8 as a carrier to enhance production and/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of rPfMSP8 as a carrier to optimize a rPfMSP2-based subunit vaccine. rPfMSP2 and chimeric rPfMSP2/8 vaccines produced in Escherichia coli were evaluated in comparative immunogenicity studies in inbred (CB6F1/J) and outbred (CD1) mice, varying the dose and adjuvant. Immunization of mice with both rPfMSP2-based vaccines elicited high-titer anti-PfMSP2 Abs that recognized the major allelic variants of PfMSP2. Vaccine-induced T cells recognized epitopes present in both PfMSP2 and the PfMSP8 carrier. Competition assays revealed differences in Ab specificities induced by the two rPfMSP2-based vaccines, with evidence of epitope masking by rPfMSP2-associated fibrils. In contrast to aluminum hydroxide (Alum) as adjuvant, formulation of rPfMSP2 vaccines with glucopyranosyl lipid adjuvant–stable emulsion, a synthetic TLR4 agonist, elicited Th1-associated cytokines, shifting production of Abs to cytophilic IgG subclasses. The rPfMSP2/8 + glucopyranosyl lipid adjuvant–stable emulsion formulation induced significantly higher Ab titers with superior durability and capacity to opsonize P. falciparum merozoites for phagocytosis. Immunization with a trivalent vaccine including PfMSP2/8, PfMSP1/8, and the P. falciparum 25 kDa sexual stage antigen fused to PfMSP8 (Pfs25/8) induced high levels of Abs specific for epitopes in each targeted domain, with no evidence of antigenic competition. These results are highly encouraging for the addition of rPfMSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine.

ObjectivesThis study aimed to report the pre- and post-operative laryngeal endoscopic findings in patients referred by non-otolaryngologists who are undergoing thyroid and/or parathyroid surgery, and to determine the number and nature of referrals before and after the release of the clinical practice guideline for improving voice outcomes after thyroid surgery.MethodsThis retrospective cohort study, conducted at a tertiary care academic hospital, comprised adult patients referred by the endocrine surgery service for laryngoscopy from 2007 to 2018 (n = 166). Data regarding patient demographics, reason for referral and endoscopic findings were recorded.ResultsThe number of referrals increased significantly after the release of the practice guideline. The most common indication for referral pre- and post-operatively was voice change. The most common finding during laryngoscopy was normal examination findings (pre-operatively) and unilateral vocal fold immobility (post-operatively).ConclusionPeri-operative thyroid and/or parathyroid patients have laryngoscopic findings other than vocal fold immobility. Laryngoscopy to detect structural and functional pathology is warranted.

Purpose Previous ambulatory voice monitoring studies have included many singers and have combined speech and singing in the analyses. This study applied a singing classifier to the ambulatory recordings of singers with phonotrauma and healthy controls to determine if analyzing speech and singing separately would reveal voice use differences that could provide new insights into the etiology and pathophysiology of phonotrauma in this at-risk population. Method Forty-two female singers with phonotrauma (vocal fold nodules or polyps) and 42 healthy matched controls were monitored using an ambulatory voice monitor. Weeklong statistics (average, standard deviation, skewness, kurtosis) for sound pressure level (SPL), fundamental frequency, cepstral peak prominence, the magnitude ratio of the first two harmonics ( H 1 –H 2 ), and three vocal dose measures were computed from the neck surface acceleration signal and separated into singing and speech using a singing classifier. Results Mixed analysis of variance models found expected differences between singing and speech in each voice parameter, except SPL kurtosis. SPL skewness, SPL kurtosis, and all H 1 –H 2 distributional parameters differentiated patients and controls when singing and speech were combined. Interaction effects were found in H 1 –H 2 kurtosis and all vocal dose measures. Patients had significantly higher vocal doses in speech compared to controls. Conclusions Consistent with prior work, the pathophysiology of phonotrauma in singers is characterized by more abrupt/complete glottal closure (decreased mean and variation for H 1 –H 2 ) and increased laryngeal forces (negatively skewed SPL distribution) during phonation. Application of a singing classifier to weeklong data revealed that singers with phonotrauma spent more time speaking on a weekly basis, but not more time singing, compared to controls. Results are used as a basis for hypothesizing about the role of speaking voice in the etiology of phonotraumatic vocal hyperfunction in singers.

Background: A significant number of patients who undergo spinal fusion surgery are managed in chronic pain clinics for low back pain or what is commonly described as failed back surgery syndrome (FBSS). There are a multitude of reasons for chronic long standing back pain after surgery, and the etiology is often multifactorial involving both preoperative and postoperative risk factors. In patients with scoliosis, it has been shown that fusion with Harrington rods extending into the lumbar region is associated with increases in postoperative back pain, especially with fusions to the L4-L5 region. Spinal cord stimulation (SCS) is a recognized treatment for this condition after repeat surgery or when conservative treatments have failed. Case Report: This case report describes the use of SCS with combination therapy in the management of severe low back pain after thoracolumbar fusion with Harrington rods in a patient with congenital scoliosis. After a failed trial of conservative medical management, a spinal cord stimulator capable of delivering combination traditional paresthesia with subperception and burst stimulation was placed. Regarding the choice of SCS therapy, there is a vast array of choices including traditional paresthesia, paresthesia-free, subperception, microburst, or combination treatment. The latter is capable of delivering multiple therapies over time designed to provide more thorough and longer-lasting relief. Conclusion: Simultaneous traditional paresthesia and subperception waveform therapy might offer superior pain relief in comparison to therapies utilizing a sing=le waveform. Further studies are needed to evaluate the use of combination over traditional SCS therapy for the treatment of axial back pain secondary to FBSS. Key words: Chronic pain, combination therapy, congenital scoliosis, neuromodulation, spinal cord stimulator, spinal fusion

Purpose This study attempts to gain insights into the role of daily voice use in the etiology and pathophysiology of phonotraumatic vocal hyperfunction (PVH) by applying a logistic regression-based daily phonotrauma index (DPI) to predict group-based improvements in patients with PVH after laryngeal surgery and/or postsurgical voice therapy. Method A custom-designed ambulatory voice monitor was used to collect 1 week of pre- and postsurgery data from 27 female patients with PVH; 13 of these patients were also monitored after postsurgical voice therapy. Normative weeklong data were obtained from 27 matched controls. Each week was represented by the DPI, standard deviation of the difference between the first and second harmonic amplitudes (H1–H2). Results Compared to pretreatment, the DPI significantly decreased in the patient group after surgery (Cohen's d effect size = −0.86) and voice therapy ( d = −1.06). The patient group DPI only normalized after voice therapy. Conclusions The DPI produced the expected pattern of improved ambulatory voice use across laryngeal surgery and postsurgical voice therapy in a group of patients with PVH. The results were interpreted as providing new objective information about the role of daily voice use in the etiology and pathophysiology of PVH. The DPI is viewed as an estimate of potential vocal fold trauma that relies on combining the long-term distributional characteristics of two parameters representing the magnitude of phonatory forces (neck-surface acceleration magnitude) and vocal fold closure dynamics (H1–H2). Further validation of the DPI is needed to better understand its potential clinical use.

Summary Objectives A major limitation of comparing the efficacy of videostroboscopy (VS) and high-speed videoendoscopy (HSV) is the lack of an objective reference by which to compare the functional assessment ratings of the two techniques. For patients with vocal fold mass lesions, intraoperative measures of lesion size and depth may serve as this objective reference. This study compared the relationships between the pre- to postoperative change in VS and HSV visual-perceptual ratings to intraoperative measures of lesion size and depth. Design Prospective visual-perceptual study with intraoperative measures of lesion size and depth. Methods VS and HSV samples were obtained preoperatively and postoperatively from 28 patients with vocal fold lesions and from 17 vocally healthy controls. Two experienced clinicians rated amplitude, mucosal wave, vertical phase difference, left-right phase asymmetry, and vocal fold edge on a visual-analog scale using both imaging techniques. The change in perioperative ratings from VS and HSV was compared between groups and correlated to intraoperative measures of lesion size and depth. Results HSV was as reliable as VS for ratings of amplitude and edge, and substantially more reliable for ratings of mucosal wave and left-right phase asymmetry. Both VS and HSV had mild-moderate correlations between change in perioperative ratings and intraoperative measures of lesion area. Change in function could be obtained in more patients and for more parameters using HSV than VS. Group differences were noted for postoperative ratings of amplitude and edge; however, these differences were within one level of the visual-perceptual rating scale. The presence of asynchronicity in VS recordings renders vibratory features either uninterpretable or potentially distorted and thus should not be rated. Conclusions Amplitude and edge are robust vibratory measures for perioperative functional assessment, regardless of imaging modality. HSV is indicated for evaluation of subepithelial lesions or if asynchronicity is present in the VS image sequence.

Purpose Given the established linear relationship between neck surface vibration magnitude and mean subglottal pressure (Ps) in vocally healthy speakers, the purpose of this study was to better understand the impact of the presence of a voice disorder on this baseline relationship. Method Data were obtained from participants with voice disorders representing a variety of glottal conditions, including phonotraumatic vocal hyperfunction, nonphonotraumatic vocal hyperfunction, and unilateral vocal fold paralysis. Participants were asked to repeat /p/-vowel syllable strings from loud-to-soft loudness levels in multiple vowel contexts (/pa/, /pi/, /pu/) and pitch levels (comfortable, higher than comfortable, lower than comfortable). Three statistical metrics were computed to analyze the regression line between neck surface accelerometer (ACC) signal magnitude and Ps within and across pitch, vowel, and voice disorder category: coefficient of determination ( r 2 ), slope, and intercept. Three linear mixed-effects models were used to evaluate the impact of voice disorder category, pitch level, and vowel context on the relationship between ACC signal magnitude and Ps. Results The relationship between ACC signal magnitude and Ps was statistically different in patients with voice disorders than in vocally healthy controls; patients exhibited higher levels of Ps given similar values of ACC signal magnitude. Negligible effects were found for pitch condition within each voice disorder category, and negligible-to-small effects were found for vowel context. The mean of patient-specific r 2 values was .63, ranging from .13 to .92. Conclusions The baseline, linear relationship between ACC signal magnitude and Ps is affected by the presence of a voice disorder, with the relationship being participant-specific. Further work is needed to improve ACC-based prediction of Ps, across treatment, and during naturalistic speech production.

BackgroundThe epidemiology of congenital infections is ever changing, with a recent resurgence in syphilis infection rates seen in the UK. Identification of congenital infection is often delayed; early recognition and management of congenital infections is important. Testing modalities and investigations are often limited, leading to missed diagnostic opportunities.MethodsThe SCORTCH (syphilis, cytomegalovirus (CMV), ‘other’, rubella, toxoplasmosis, chickenpox, herpes simplex virus (HSV) and blood-borne viruses) acronym increases the awareness of clinicians to the increased risk of congenital syphilis, while considering other infectious aetiologies including: zika, malaria, chagas disease, parvovirus, enterovirus, HIV, hepatitis B and C, and human T-lymphotropic virus 1, in addition to the classic congenital infections recognised in the ‘TORCH screen’ (toxoplasmosis, ‘other’, rubella, CMV, HSV). The SCORTCH diagnostic approach describes common signs present in infants with congenital infection, details serological testing for mother and infant and important direct diagnostics of the infant. Direct diagnostic investigations include: radiology, ophthalmology, audiology, microbiological and PCR testing for both the infant and placental tissue, the latter also warrants histopathology.ConclusionThe traditional ‘TORCH screen’ focuses on serology-specific investigations, often omits important direct diagnostic testing of the infant, and fails to consider emerging and re-emerging congenital infections. In recognition of syphilis as a re-emerging pathogen and the overlapping clinical presentations of various infectious aetiologies, we advocate for a broader outlook using the SCORTCH diagnostic approach.

Irritability is a substrate of more than one dozen clinical syndromes. Thus, identifying when it is atypical and interfering with functioning is crucial to the prevention of mental disorder in the earliest phase of the clinical sequence. Advances in developmentally based measurement of irritability have enabled differentiation of normative irritable mood and tantrums from indicators of concern, beginning in infancy. However, developmentally sensitive assessments of irritability-related impairment are lacking. We introduce the Early Childhood Irritability-Related Impairment Interview (E-CRI), which assesses impairment associated with irritable mood and tantrums across contexts. Reliability and validity are established across two independent samples varied by developmental period: the Emotional Growth preschool sample (EmoGrow; N = 151, M = 4.82 years) and the When to Worry infant/toddler sample (W2W; N = 330, M = 14 months). We generated a well-fitting two-factor E-CRI model, with tantrum- and irritable mood-related impairment factors. The E-CRI exhibited good interrater, test–retest, and longitudinal reliability. Construct and clinical validity were also demonstrated. In both samples, E-CRI factors showed association to internalizing and externalizing problems, and to caregiver-reported concern in W2W. Tantrum-related impairment demonstrated stronger and more consistent explanatory value across outcomes, while mood-related impairment added explanatory utility for internalizing problems. The E-CRI also showed incremental utility beyond variance explained by the Family Life Impairment Scale (FLIS) survey indicator of developmental impairment. The E-CRI holds promise as an indicator of impairment to inform identification of typical versus atypical patterns reflecting early emerging irritability-related syndromes in the initial phase of the clinical sequence.

Purpose Adductor spasmodic dysphonia (ADSD), the most common form of spasmodic dysphonia, is a debilitating voice disorder characterized by hyperactivity and muscle spasms in the vocal folds during speech. Prior neuroimaging studies have noted excessive brain activity during speech in participants with ADSD compared to controls. Speech involves an auditory feedback control mechanism that generates motor commands aimed at eliminating disparities between desired and actual auditory signals. Thus, excessive neural activity in ADSD during speech may reflect, at least in part, increased engagement of the auditory feedback control mechanism as it attempts to correct vocal production errors detected through audition. Method To test this possibility, functional magnetic resonance imaging was used to identify differences between participants with ADSD ( n = 12) and age-matched controls ( n = 12) in (a) brain activity when producing speech under different auditory feedback conditions and (b) resting-state functional connectivity within the cortical network responsible for vocalization. Results As seen in prior studies, the ADSD group had significantly higher activity than the control group during speech with normal auditory feedback (compared to a silent baseline task) in three left-hemisphere cortical regions: ventral Rolandic (sensorimotor) cortex, anterior planum temporale, and posterior superior temporal gyrus/planum temporale. Importantly, this same pattern of hyperactivity was also found when auditory feedback control of speech was eliminated through masking noise. Furthermore, the ADSD group had significantly higher resting-state functional connectivity between sensorimotor and auditory cortical regions within the left hemisphere as well as between the left and right hemispheres. Conclusions Together, our results indicate that hyperactivation in the cortical speech network of individuals with ADSD does not result from hyperactive auditory feedback control mechanisms and rather is likely related to impairments in somatosensory feedback control and/or feedforward control mechanisms.

Excessive weight gain has been reported with integrase strand transfer inhibitors (INSTIs). We evaluated weight changes in virologically suppressed adults with HIV who switched from non-INSTI regimens to raltegravir (RAL)-containing or dolutegravir (DTG)-containing antiretroviral therapy.Retrospective single-centre cohort.Adults who switched to RAL or DTG before or between January 2015 and October 2017 were identified. Virologically suppressed, treatment-experienced (≥2 years) individuals, at least 6 months on INSTI, with weight measurements 2 years or less pre and postswitch were included. Our analysis used a random effects model with linear slope pre and post-INSTI with adjustment for age, sex, ethnicity, preswitch-regimen (protease inhibitor vs. nonprotease inhibitor), and RAL vs. DTG use.A total of 378 individuals, 81.2% male, 70.1% white ethnicity, median age of 49 years, median of four weight measurements per participant, and median weight and BMI at switch of 76.6 kg and 25.3 kg/m, respectively, were included. Weight increased by an average of 0.63 kg/year (95% confidence interval 0.17-1.09) preswitch with no overall change in rate of weight gain postswitch [+0.05 kg/year (-0.61-0.71, P = 0.88)]. In our adjusted model, a transition from minimal weight change to weight gain postswitch was isolated to older individuals though this lacked statistical significance [e.g., +1.59 kg/year (-0.26-3.45) if aged 65 years]. Our findings did not differ by sex, ethnicity, preswitch regimen, or RAL vs. DTG. Similar results were seen for BMI and after adjusting for fixed nucleoside/nucleotide reverse transcriptase inhibitor backbone.We found no clear evidence of an overall increase in rate of weight gain following switch to INSTI in virologically suppressed individuals.

The integration of neurodevelopmental perspectives into clinical science has identified irritability as an early dimensional marker of lifespan mental health risk. Elucidating the developmental patterning of irritable behavior is key to differentiating normative variation from risk markers. Accounting for dysregulation and contextual features of irritability is useful for differentiation at preschool age, laying the groundwork for even earlier characterization. We provide initial evidence for the validity of the Multidimensional Assessment Profile of Disruptive Behavior Temper Loss Scale, Infant-Toddler version in two independent samples of 12-18-month-olds from the US. We calibrated the measure using item response theory in a large representative sample, then validated within an independent sample. We characterized the developmental patterning of irritable behaviors and their dimensional spectrum, and demonstrated test-retest reliability, and convergent validity. The MAP-DB-IT is a standardized, dimensional survey assessing irritability that serves as a tool for characterizing the developmental expression of early mental health risk.

OBJECTIVES Integrase strand transfer inhibitors (INSTIs) are commonplace in modern antiretroviral therapy (ART). Increased weight gain with their use is increasingly scrutinized. We evaluated weight changes in treatment-naive adults with HIV-1 attending a UK centre who started regimens including raltegravir or dolutegravir. METHODS A retrospective cohort study of adults prescribed an INSTI between January 2015 and March 2020 were categorized as having started an ART regimen containing raltegravir, dolutegravir, a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Individuals with one or more weight measurement ≤ 5 years both pre- and post-ART initiation, who started a three-drug regimen with ≥ 6 months duration and achieved virological suppression (

Purpose The aim of this study was to use the Daily Phonotrauma Index (DPI) to quantify group-based changes in the daily voice use of patients with phonotraumatic vocal hyperfunction (PVH) after receiving voice therapy as the sole treatment. This is part of an ongoing effort to validate an updated theoretical framework for PVH. Method A custom-designed ambulatory voice monitor was used to collect 1 week of pre- and posttreatment data from 52 female patients with PVH. Normative weeklong data were also obtained from 52 matched controls. Each week was represented by the DPI, which is a combination of neck-surface acceleration magnitude skewness and the standard deviation of the difference between the first and second harmonic magnitudes. Results Compared to pretreatment, the DPI statistically decreased towards normal in the patient group after treatment (Cohen's d = −0.25). The posttreatment patient group's DPI was still significantly higher than the control group ( d = 0.68). Conclusions The DPI showed the pattern of improved ambulatory voice use in a group of patients with PVH following voice therapy that was predicted by the updated theoretical framework. Per the prediction, voice therapy was associated with a decreased potential for phonotrauma in daily voice use, but the posttreatment patient group data were still significantly different from the normative control group data. This posttreatment difference is interpreted as reflecting the impact on voice use of the persistence of phonotrauma-induced structural changes to the vocal folds. Further validation of the DPI is needed to better understand its potential clinical use.

Facilitated attention toward angry stimuli (attention bias) may contribute to anger proneness and temper outbursts exhibited by children with high irritability. However, most studies linking attention bias and irritability rely on behavioral measures with limited precision and no studies have explored these associations in young children. The present study explores irritability-related attention biases toward anger in young children (N = 128; ages 4-7 years) engaged in a dot-probe task with emotional faces, as assessed with event-related brain potential (ERP) indices of early selective attention and multi-method assessment of irritability. Irritability assessed via semi-structured clinical interview predicted larger anterior N1 amplitudes to all faces. In contrast, irritability assessed via a laboratory observation paradigm predicted reduced P1 amplitudes to angry relative to neutral faces. These findings suggest that altered early attentional processing occurs in young children with high irritability; however, the nature of these patterns may vary with methodological features of the irritability assessments. Future investigations using different assessment tools may provide greater clarity regarding the underlying neurocognitive correlates of irritability. Such studies may also contribute to the ongoing debates about how to best define and measure irritability across the developmental spectrum in a manner that is most informative for linkage to neural processes.

Vaccine trials and cohort studies in Plasmodium falciparum endemic areas indicate that naturally-acquired and vaccine-induced antibodies to merozoite surface protein 2 (MSP2) are associated with resistance to malaria. These data indicate that PfMSP2 has significant potential as a component of a multi-antigen malaria vaccine. To overcome challenges encountered with subunit malaria vaccines, we established that the use of highly immunogenic rPfMSP8 as a carrier protein for leading vaccine candidates rPfMSP119 and rPfs25 facilitated antigen production, minimized antigenic competition and enhanced induction of functional antibodies. We applied this strategy to optimize a rPfMSP2 (3D7)-based subunit vaccine by producing unfused rPfMSP2 or chimeric rPfMSP2/8 in Escherichia coli. rPfMSP2 formed fibrils, which induced splenocyte proliferation in an antigen receptor-independent, TLR2-dependent manner. However, fusion to rPfMSP8 prevented rPfMSP2 amyloid-like fibril formation. Immunization of rabbits elicited high-titer anti-PfMSP2 antibodies that recognized rPfMSP2 of the 3D7 and FC27 alleles, as well as native PfMSP2. Competition assays revealed a difference in the specificity of antibodies induced by the two rPfMSP2-based vaccines, with evidence of epitope masking by rPfMSP2-associated fibrils. Rabbit anti-PfMSP2/8 was superior to rPfMSP2-elicited antibody at opsonizing P. falciparum merozoites for phagocytosis. These data establish rPfMSP8 as an effective carrier for a PfMSP2-based subunit malaria vaccine.

BACKGROUND: There are limited data examining the risk of prostate cancer (PCa) in patients with inflammatory bowel disease (IBD). OBJECTIVE: To compare the incidence of PCa between men with and those without IBD. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, matched-cohort study involving a single academic medical center and conducted from 1996 to 2017. Male patients with IBD (cases = 1033) were randomly matched 1:9 by age and race to men without IBD (controls = 9306). All patients had undergone at least one prostate-specific antigen (PSA) screening test. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier and multivariable Cox proportional hazard models, stratified by age and race, evaluated the relationship between IBD and the incidence of any PCa and clinically significant PCa (Gleason grade group ≥2). A mixed-effect regression model assessed the association of IBD with PSA level. RESULTS AND LIMITATIONS: PCa incidence at 10 yr was 4.4% among men with IBD and 0.65% among controls (hazard ratio [HR] 4.84 [3.34–7.02] [3.19–6.69], p < 0.001). Clinically significant PCa incidence at 10 yr was 2.4% for men with IBD and 0.42% for controls (HR4.04 [2.52–6.48], p < 0.001). After approximately age 60, PSA values were higher among patients with IBD (fixed-effect interaction of age and patient group: p = 0.004). Results are limited by the retrospective nature of the analysis and lack of external validity. Conclusions: Men with IBD had higher rates of clinically significant PCa when compared with age- and race-matched controls. PATIENT SUMMARY: This study of over 10 000 men treated at a large medical center suggests that men with inflammatory bowel disease may be at a higher risk of prostate cancer than the general population.

OBJECTIVES/HYPOTHESIS Photoangiolytic precision afforded by the 532-nm potassium-titanyl-phosphate (KTP) laser relies on predictable energy delivery. Inadequate energy output can cause vessel rupture, and excessive energy can cause thermal damage. The quality of the cleaved surface and carbon deposits from ablated tissue are two factors that could negatively impact fiber performance. The effects of these on energy output and blood vessel coagulation were assessed using a chorioallantoic membrane (CAM) model. STUDY DESIGN Comparative analysis. METHODS Laser fibers with carbon debris, optimal fiber cleaving, and suboptimal cleaving were inspected at three times magnification, and the light dispersion pattern of each fiber was rated. The average energy output from consecutive pulses through each fiber configuration was recorded. The effect of these fiber conditions on clinical efficacy was estimated by measuring vessel coagulation versus rupture in the CAM model. Repeated measures analysis of variance compared results. RESULTS Carbon debris and suboptimal cleaving resulted in decreased energy output in comparison to optimal cleaving ([-Δ244 mJ, d = 4.31, P

OBJECTIVES While it is acknowledged that otolaryngologists performing microlaryngeal surgery can develop musculoskeletal symptoms due to suboptimal body positioning relative to the patient, flexible laryngoscopy and awake laryngeal surgeries (ALSs) can also pose ergonomic risk. This prospective study measured the effects of posture during ergonomically good and bad positions during laryngoscopy using ergonomic analysis, skin-surface electromyography (EMG), and self-reported pain ratings. STUDY DESIGN Prospective cohort study. METHODS Eight participants trained in laryngoscopy assumed four ergonomically distinct standing positions (side/near, side/far, front/near, front/far) at three different heights (neutral-top of patient's head in line with examiner's shoulder, high-6 inches above neutral, and low-6 inches below neutral) in relation to a simulated patient. Participants' postures were analyzed using the validated Rapid Upper Limb Assessment (RULA, 1 [best] to 7 [worst]) tool for the 12 positions. Participants then simulated ALS for 10 minutes in a bad position (low-side-far) and a good position (neutral-front-near) with 12 EMG sensors positioned on the limbs and torso. RESULTS The position with the worst RULA score was the side/near/high (7.0), and the best was the front/near/neutral (4.5). EMG measurements revealed significant differences between simulated surgery in the bad and good positions, with bad position eliciting an average of 206% greater EMG root-mean-squared magnitude across all sampled muscles compared to the good posture (paired t-test, df = 7, P

Objective: To investigate the indications, efficacy, safety, and outcomes of potassium-titanyl-phosphate (KTP) laser procedures for treatment of laryngeal disease. Methods: PubMed, Cochrane Library, and Scopus were searched for studies providing information about the indications, efficacy, and safety of both in-office and operative suspension microlaryngoscopy KTP laser procedure in treatment of laryngeal disease. Diagnostic criteria and clinical outcome evaluation of included studies were analyzed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Results: Of the initial screened 140 papers, 17 met our inclusion criteria. Six papers involved KTP laser procedures for benign and malignant vocal fold lesions in suspension microlaryngoscopy only, 10 papers focused on only in-office KTP laser procedures for benign vocal fold lesions, and 1 paper included both in-office and suspension microlaryngoscopy procedures. The following lesions may be considered as indications for KTP laser procedures: Reinke’s edema, sulcus vocalis, vocal fold hemorrhage, polyp, granuloma, cyst, scar, papillomatosis, dysplasia, leukoplakia, and early vocal fold malignancies. Irrespective of the types of procedure (in-office vs suspension microlaryngoscopy), the KTP laser is associated with a low complication rate and overall good vocal fold vibration recovery. There is an important heterogeneity among studies concerning laser settings, indications, and outcomes used for the assessment of treatment effectiveness. There are no controlled studies directly comparing KTP laser with other lasers (ie, carbon dioxide laser). Conclusion: The use of KTP laser procedures for treatment of laryngeal disease has increased over the past decade, especially for office-based management of vocal fold lesions. Future controlled studies are needed to compare the safety and outcomes of the KTP laser to other techniques.

Purpose: Young adults with cancer often experience stress, depression, and anxiety. Mindfulness meditation is an effective intervention for these outcomes, and maintenance support may be needed for long-term improvements. eHealth technologies provide a promising delivery strategy for maintenance interventions. Methods: Following an 8-week mindfulness-based stress reduction (MBSR) course, 62 young adult cancer survivors were randomized to 8 weeks of instructor-framed messages, peer-framed messages, or no messages. On average, participants were 33.6 years old. The majority of participants were college-educated Caucasian females. We examined attrition rates between participants who received messages and those who did not, and compared response rates from different perceived sources. In addition, we evaluated the preliminary effects of eHealth support on mindfulness and associated outcomes. Results: No significant differences in attrition or message response rates across groups were observed. Repeated measures models revealed significant group by time interactions on perceived stress, anxiety, and depression. There were no differences between the groups that received eHealth messages and the group that did not. There was a significant difference in anxiety symptoms from post-MBSR to post-messaging between messaging groups. Individuals who received instructor-framed messages reported increased symptoms of anxiety over time. Conclusion: Attrition and response rates did not differ across groups, suggesting that eHealth may be a feasible strategy for providing maintenance support. However, further evaluation of feasibility, acceptability, and optimal content and dose of such an intervention is needed. Additionally, young adult cancer survivors may be more likely to benefit from eHealth interventions that are not delivered by authority figures.

Covid-19 (SARS-CoV-2) is a new coronavirus. Since the declaration of a global pandemic, a lot has been learnt about its spread, disease pattern, diagnosis and management. The lungs remain the prime organs to incur serious insult and when lung complications embark, significant morbidity and mortality is observed. Predominantly, patchy and peripheral lung distribution in the Covid-19 pneumonia has been described in the radiology experience and literature. There are a range of imaging modes useable in diagnosis, prognosis, monitoring, and therapy of Covid-19. However, when it comes to the appropriateness and the potential benefits of imaging, resource utilization and infectious risk must be considered. The use of ultrasound during this pandemic has provided us with an alternate imaging modality that is easily performed at the bedside, with real time images available to the clinician. This case highlights the role played by the thoracic ultrasound in the diagnosis and progression of Covid-19 pneumonia.

AimTo capture the direct and indirect cost estimates of dry eye disease (DED), stratified by disease severity, in patients from Canada and to understand the impact of DED on quality of life (QoL) in this group.MethodsA prospective, multi-centre, observational, cross-sectional study was conducted at six optometry and ophthalmology sites across Canada. Eligible patients completed a 20-minute survey on demography, general health, disease severity, QoL, and direct and indirect costs.ResultsA total of 151 patients participated in the study and 146 were included in the analysis. Mean (standard deviation [SD]) age was 49.8 (11.4) years and most patients were female (89.7%). DED was considered moderate or severe by 19.2% and 69.2% of patients, respectively. Sjögren’s syndrome was reported by 8.2% of patients. Total mean annual costs of DED were $24,331 (Canadian dollars [CAD]) per patient and increased with disease severity. Mean (SD) indirect costs for mild, moderate, and severe disease were $5,961 ($6,275), $16,525 ($11,607), and $25,485 ($22,879), respectively. Mean (SD) direct costs were $958 ($1,216), $1,303 ($1,574), and $2,766 ($7,161), respectively. QoL scores were lowest in patients with Sjögren’s syndrome and those with severe DED.ConclusionsThis study provides important insights into the negative impact of DED in a Canadian setting. Patients with severe DED reported higher direct and indirect costs and lower QoL compared with those with mild or moderate disease. Increased costs and poorer QoL were also evident for patients with DED plus Sjögren’s syndrome versus DED alone.

Objectives: Prevention, diagnosis, and treatment of hyperfunctional voice disorders would be improved by better understanding their etiological contributing factors. Therefore, this study estimated the prevalence of etiological factors using self-reported data about disorder onset from a large cohort of patients with Phonotraumatic Vocal Hyperfunction (PVH) and Non-Phonotraumatic Vocal Hyperfunction (NPVH). Methods: Retrospective chart review extracted the self-reported rate (gradual, sudden) and events associated (voice use, anxiety/stress, upper respiratory infection [URI]) with disorder onset from 1,577 patients with PVH and 979 patients with NPVH. Results: Both patient groups reported a gradual onset more than a sudden onset. Voice use was the most frequently reported event for PVH and the NPVH group self-reported all three events at equal frequency. The largest PVH subgroups were associated with voice use while the NPVH subgroups were associated with only voice use, only URI, or only anxiety/stress. Conclusion: The results support the general clinical view that PVH is most strongly related to the gradual accumulated effects of phonotrauma, while NPVH has a more heterogeneous etiology. The identified PVH and NPVH subgroups may have clinical relevance and future work could investigate differences in treatment and outcomes among these subgroups.

Low birth weight (LBW) is associated with significant mortality and morbidity and remains a significant preventable problem. Risk factors include socioeconomic, demographics, and characteristics of the environment. Spatial analysis can uncover unusual frequencies of health problems in neighborhoods, eventually leading to insights for targeted interventions. This study's goals were to 1. Evaluate the geographic distribution of spatial clusters of LBW births and maternal risk factors. 2. Determine the spatial relationship between risk factors and LBW. This study obtained data on LBW newborns and risk factors from 19,013 births over 5 years (2012–2016) for Escambia County Census Tracts, extracted from FloridaCharts.com. Software was used to detect significant spatial clusters; these clusters were then plotted on a map. Poisson regression determined the statistical relationship between Census Tract risk factors and LBW. A separate analysis of the LBW cluster controlling for risk factors was also performed. All risk factor clusters resided in similar locations as the LBW cluster. The multiple Poisson regression model containing all risk factors fully explained the LBW cluster. On bivariate Poisson regression all risk factors in the Census Tract were significantly related to LBW whereas in multivariable Poisson regression, the proportion of births to African American women in the Census Tract remained significant after adjusting for other risk factors (p

The pharmacogenomic network responsible for the rapid antidepressant action of ketamine and concomitant adverse events in patients has been poorly defined. Integrative, multi-scale biological data analytics helps explain ketamine’s action. Using a validated computational pipeline, candidate ketamine-response genes and regulatory RNAs from published literature, binding affinity studies, and single nucleotide polymorphisms (SNPs) from genomewide association studies (GWAS), we identified 108 SNPs associated with 110 genes and regulatory RNAs. All of these SNPs are classified as enhancers, and additional chromatin interaction mapping in human neural cell lines and tissue shows enhancer-promoter interactions involving other network members. Pathway analysis and gene set optimization identified three composite sub-networks within the broader ketamine pharmacogenomic network. Expression patterns of ketamine network genes within the postmortem human brain are concordant with ketamine neurocircuitry based on the results of 24 published functional neuroimaging studies. The ketamine pharmacogenomic network is enriched in forebrain regions known to be rapidly activated by ketamine, including cingulate cortex and frontal cortex, and is significantly regulated by ketamine (p=6.26E-33; Fisher’s exact test). The ketamine pharmacogenomic network can be partitioned into distinct enhancer sub-networks associated with: (1) glutamate neurotransmission, chromatin remodeling, smoking behavior, schizophrenia, pain, nausea, vomiting, and post-operative delirium; (2) neuroplasticity, depression, and alcohol consumption; and (3) pharmacokinetics. The component sub-networks explain the diverse action mechanisms of ketamine and its analogs. These results may be useful for optimizing pharmacotherapy in patients diagnosed with depression, pain or related stress disorders.One Sentence SummaryThe ketamine network in the human brain consists of sub-networks associated with glutamate neurotransmission, neuroplasticity, and pharmacokinetics.

Purpose Previous work using ambulatory voice recordings has shown no differences in average vocal behavior between patients with phonotraumatic vocal hyperfunction and matched controls. This study used larger groups to replicate these results and expanded the analysis to include distributional characteristics of ambulatory voice use and measures indicative of glottal closure. Method Subjects included 180 adult women: 90 diagnosed with vocal fold nodules or polyps and 90 age-, sex-, and occupation-matched controls with no history of voice disorders. Weeklong summary statistics (average, variability, skewness, kurtosis) of voice use were computed from neck-surface acceleration recorded using an ambulatory voice monitor. Voice measures included estimates of sound pressure level (SPL), fundamental frequency ( f o ), cepstral peak prominence, and the difference between the first and second harmonic magnitudes (H1–H2). Results Statistical comparisons resulted in medium–large differences (Cohen's d ≥ 0.5) between groups for SPL skewness, f o variability, and H1–H2 variability. Two logistic regressions (theory-based and stepwise) found SPL skewness and H1–H2 variability to classify patients and controls based on their weekly voice data, with an area under the receiver operating characteristic curve of 0.85 and 0.82 on training and test sets, respectively. Conclusion Compared to controls, the weekly voice use of patients with phonotraumatic vocal hyperfunction reflected higher SPL tendencies (negatively skewed SPL) with more abrupt glottal closure (reduced H1–H2 variability, especially toward higher values). Further work could examine posttreatment data (e.g., after surgery and/or therapy) to determine the extent to which these differences are associated with the etiology and pathophysiology of phonotraumatic vocal fold lesions.

Background Congenital cytomegalovirus (CCMV) accounts for high rates of infant morbidity and mortality. Neutropenia is a common finding in CCMV infection, of which the age of presentation overlaps with autoimmune neutropenia (AIN). AIN represents one of the most common forms of chronic neutropenia in childhood. Methods A literature search exploring biologic associations between CCMV and AIN was conducted: PubMed (MEDLINE), Ovid and Web of Science. We further describe 2 cases of concurrent CCMV and AIN. Both cases were confirmed with the indirect granulocyte immunofluorescence test and alternative etiologies for neutropenia excluded. Results Our 2 patients represent confirmed cases of AIN in infants with CCMV. One patient demonstrated neutropenia while undergoing treatment with Valganciclovir, while the other was never treated. With interruption of Valganciclovir in infant A, neutrophil counts (ANC) did not improve and upon resumption of treatment ANC remained static. Conclusions Further studies examining a possible biologic link between CCMV and AIN are advocated for. We encourage clinicians to actively consider AIN in the differential diagnosis of all infants with CCMV presenting with neutropenia.

Objectives: Prognostic information about the return of vocal fold mobility in patients with iatrogenic unilateral vocal fold immobility (UVFI) can help with informed decisions about temporary and permanent treatment options. Although many variables can influence the likelihood of recovery, clinical experience suggests that cervical versus thoracic injury is a determining factor. The purpose of this study was to compare recovery rates from UVFI between cervical and thoracic injuries. Methods: A retrospective review of the medical record was performed on all adult patients diagnosed with complete iatrogenic UVFI from 2005 to 2015 (n = 923). Patients with incomplete data and etiologies of idiopathic, malignancy, or stenosis were excluded, leaving a study cohort of 502 patients who were categorized as having UVFI after cervical (n = 329) or thoracic (n = 173) injury. Data regarding site of iatrogenic injury (cervical vs thoracic), mobility status, and time interval to recovery or surgical intervention were recorded and compared using χ2 analyses. Results: Overall, 15% of patients recovered vocal fold mobility at a median of 4.1 months. Patients with cervical injury (65 of 329 [20%]) were significantly more likely to recover mobility than patients with thoracic injury (11 of 173 [6.4%]) (odds ratio, 3.63). The cervical cohort contained more women (68% vs 31%) and was younger (mean age, 60.4 ± 13.8 vs 64.1 ± 16.1 years; Cohen’s D = 0.25). Conclusions: Patients with cervical injuries resulting in UVFI are 4 times more likely to recover mobility than patients with thoracic injuries. This information can be valuable in counseling patients with UVFI and may affect clinical decision making.

Irritability is a prominent feature of chronic mental disorders and a developmental marker of their early emergence. The most salient feature of irritability in early childhood is temper tantrums. While temper tantrums are normative in young children, they can be clinically concerning when they are dysregulated, very frequent, and/or occur in unexpected contexts. The present study uses behavioral and event-related brain potential (ERP) measures to characterize the relationship between irritability and neural markers of response inhibition in very young children. Forty-six children (ages 4–7 years) completed a go/no-go task under nonfrustrating and frustrating conditions. ERPs elicited by go and no-go stimuli were examined as a function of frustration condition and irritability, operationalized via the well-validated Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB). Higher Temper Loss scores were associated with larger N2(no-go) amplitudes and reduced no-go accuracy during frustration. This suggests that higher levels of irritability corresponded with increased conflict monitoring and poorer task performance during frustration. These findings add to a developing literature identifying the neurocognitive markers of varying levels of irritability in young children.

Disruptive behavior in childhood is common. It spans from normative child misbehaviors to clinically-significant and impairing problems. While there are many rating scales evaluating such behaviors, historically, measurement has emphasized counting the number of symptoms present rather than assessing the normal-abnormal spectrum of behavioral expression. This study uses data from 644 early school age children aggregated from two data sources to statistically link a commonly used symptom count measure, the Child Behavior Checklist (CBCL), to a more developmentally-sensitive measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB). Two links between conceptually similar scales on each measure were developed: CBCL Conduct Problems and MAP-DB Aggression; and CBCL Oppositional Defiant Problems and MAP-DB Temper Loss. We compared two innovative methods-Item Response Theory (IRT) and Deming regression-to determine the optimal linking relationship. Results suggest IRT methods were superior in reducing linking error compared to Deming regression. While Deming regression accurately modeled the mean scores (thus minimizing linking bias), this method could not adequately address the floor effect for scores on the CBCL. For practical purposes, this study provides a crosswalk of score conversions between the CBCL and MAP-DB, such that data aggregation and group comparisons can be made across the two measures; this enables longitudinal analyses with historically-collected CBCL data to transition to the more innovative dimensional scales of the MAP-DB without undo loss of extant data. This study furthers efforts to shift from historical symptom counts to more developmentally-sensitive measurement across the disruptive behaviors spectrum.

OBJECTIVES/HYPOTHESIS Wound healing after transoral angiolytic laser surgery for early glottic carcinoma was analyzed to identify factors influencing healing and clinical significance of persistent granulation tissue. STUDY DESIGN Retrospective review. METHODS A retrospective review of 100 consecutive patients undergoing endoscopic angiolytic laser surgery for T1 and T2 glottic carcinoma was performed. Patients with prior radiation or incomplete data were excluded. Postoperative endoscopic images were analyzed for time to healing, size and location of wound, and presence of granulation tissue. Three blinded, independent raters graded wound appearance and presence of granulation tissue. RESULTS Seventy-nine patients healed without need for intervention at a median of 3.5 months. Two patients had office-based ablation of granulation without biopsy and healed. The remaining 19 patients had biopsy for granulation tissue. Wounds that underwent biopsy at >3 months were more likely to contain carcinoma (5/6 patients, 83%) than wounds that were biopsied 75%vocal fold length (P = .006), and depth into muscle (P = .001). Delayed healing (>3 months) correlated with T2b tumors (P = .02), depth into ligament (P = .002) and anterior commissure involvement (P = .04). T1a carcinomas more commonly healed in 3 months warrants biopsy due to increased risk of malignancy. LEVEL OF EVIDENCE 4 Laryngoscope, 129:435-440, 2019.

To compare the physical characteristics of 3 laser-protected endotracheal tubes (LPETs) commonly used in endoscopic laser surgery. To report potential intraoperative problems related to LPET use and suggest practical solutions.Comparative analysis.Academic laboratory.Physical characteristics of the Mallinckrodt Laser-Flex (MTL), Medtronic Laser-Shield II (ML-II), and Rusch LaserTubus (RL) were compared. The effect of bending LPETs on airflow resistance was estimated with a pressure transducer. The force required to pull each tube through the glottis and the pressure exerted during this maneuver were measured in a fresh cadaveric human larynx.The design features and physical characteristics of LPETs differ, including varying balloon-tip lengths. Bending LPETs to acute angles caused significant pressure increase within the RL tube (Δ 3.42 cm HThe ML-II tube had the most favorable characteristics, with minimal pressure during extubation and resistance to kinking. The RL tube kinks readily with a resultant increase in resistance to airflow. The MTL tube extends farther into the trachea due to a relatively elongated balloon-tip configuration. Future LPET designs should incorporate features that avoid intraoperative difficulties related to airway protection and ventilation.

This study applies data science approaches (random forest and logistic regression) to determine the extent to which macro-scale corrosion damage features govern the crack formation behavior in AA7050-T7451. Each corrosion morphology has a set of corresponding predictor variables (pit depth, volume, area, diameter, pit density, total fissure length, surface roughness metrics, etc.) describing the shape of the corrosion damage. The values of the predictor variables are obtained from white light interferometry, x-ray tomography, and scanning electron microscope imaging of the corrosion damage. A permutation test is employed to assess the significance of the logistic and random forest model predictions. Results indicate minimal relationship between the macro-scale corrosion feature predictor variables and fatigue crack initiation. These findings suggest that the macro-scale corrosion features and their interactions do not solely govern the crack formation behavior. While these results do not imply that the macro-features have no impact, they do suggest that additional parameters must be considered to rigorously inform the crack formation location.

OBJECTIVE Limited studies have examined the association between diabetes and HbA1c with postoperative outcomes. We investigated the association of diabetes, defined categorically, and the association of HbA1c as a continuous measure, with postoperative outcomes. RESEARCH DESIGN AND METHODS In this prospective, observational study, we measured the HbA1c of surgical inpatients age ≥54 years at a tertiary hospital between May 2013 and January 2016. Patients were diagnosed with diabetes if they had preexisting diabetes or an HbA1c ≥6.5% (48 mmol/mol) or with prediabetes if they had an HbA1c between 5.7 and 6.4% (39 and 48 mmol/mol). Patients with an HbA1c RESULTS Of 7,565 inpatients, 30% had diabetes, and 37% had prediabetes. After adjusting for age, Charlson comorbidity index (excluding diabetes and age), estimated glomerular filtration rate, and length of surgery, diabetes was associated with increased 6-month mortality (adjusted odds ratio [aOR] 1.29 [95% CI 1.05–1.58]; P = 0.014), major complications (1.32 [1.14–1.52]; P < 0.001), intensive care unit (ICU) admission (1.50 [1.28–1.75]; P < 0.001), mechanical ventilation (1.67 [1.32–2.10]; P < 0.001), and hospital length of stay (LOS) (adjusted incidence rate ratio [aIRR] 1.08 [95% CI 1.04–1.12]; P < 0.001). Each percentage increase in HbA1c was associated with increased major complications (aOR 1.07 [1.01–1.14]; P = 0.030), ICU admission (aOR 1.14 [1.07–1.21]; P < 0.001), and hospital LOS (aIRR 1.05 [1.03–1.06]; P < 0.001). CART analysis confirmed a higher risk of 6-month mortality with diabetes in conjunction with other risk factors. CONCLUSIONS Almost one-third of surgical inpatients age ≥54 years had diabetes. Diabetes and higher HbA1c were independently associated with a higher risk of adverse outcomes after surgery.

The remaining fatigue life for aluminum aerospace alloys is greatly reduced by the presence of corrosion damage; prediction of this deleterious influence via standard fracture mechanics methods is non-trivial. Several corrosion morphologies can develop depending on the local chemistry, pH and electrochemical potential along the geometry of the structure. Previous studies demonstrate that such variations in corrosion morphology can affect the fatigue behavior. This study aims to quantify the effect of corrosion morphologies relevant to a fastener-hole geometry of AA7050-T7451 on the initiation life, propagation life and total fatigue life. Four corrosion morphologies are considered: shallow and deep discrete pits widely distributed on the corroded surface, deep fissure-like features, and general corrosion with surface recession. Corrosion morphologies are carefully characterized using optical microscope, white light interferometer and X-ray computed tomography. The samples are subjected to fatigue using loading protocols that create identifiable marks on the fracture surface at known cycle count. These marker bands are used to determine the small scale crack growth rate (da/dN) of the samples, as well as the cycles to initiate a 10 μm crack. Results showed that initiation life plateaus to near constant values for varied corrosion morphologies, and crack growth rates converge to comparable values. The macro-scale corrosion metrics are considered and correlated to the location of the fatigue initiation. Severe macro-scale metrics such as pit or fissure depth, pit mouth surface area, pit volume, pit density, root mean square, peak density, maximum valley depth, do not uniquely correlate with the location of fatigue crack initiation. This suggests a strong role of micro-scale corrosion features and underlying microstructural features on the location of the fatigue crack initiation.

There is growing support from the Accreditation Council for Graduate Medical Education and the Joint Commission of Accreditation of Health Care Organizations for a competency-based evaluation of medical and surgical performance. This is part of the quality movement in health care whereby the Centers for Medicare and Medicaid Services and third-party insurance companies have begun to link reimbursement incentives to positive surgical outcomes. Laryngeal and airway surgery require precise technique and significant mastered skill that can be difficult to obtain during otolaryngology residency training. Simulators are useful for developing laryngeal and airway surgery skills ultimately evaluated in a competency-based manner.

Background We previously demonstrated a gene-by-prenatal-environment interaction whereby the monoamine oxidase A gene (MAOA) modified the impact of prenatal tobacco exposure (PTE) on adolescent disruptive behavior (DB), with the MAOA risk genotype varying by sex. We extend this work by examining whether this mechanism is evident with another common adversity, prenatal stress exposure (PSE), and whether sex differences are present earlier in development in closer proximity to exposure. Methods Participants were 281 mothers and their 285 children derived from a prenatal cohort with in-depth prospective measures of PSE and PTE. We assessed DB at age 5 via dimensional developmentally-sensitive measurement. Analyses were stratified by sex based on prior evidence for sex differences. Results Concurrent stress exposure predicted DB in children (β = 0.310, p = 0.001), while main effects of prenatal exposures were seen only in boys. We found a three-way interaction of MAOA × PSE × sex on DB (β = 0.813, p = 0.022). Boys with MAOA-H had more DB as a function of PSE, controlling for PTE (β = 0.774, p = 0.015), and as a function of PTE, controlling for PSE (β = 0.362, p = 0.037). Boys with MAOA-L did not show this susceptibility. MAOA did not interact with PSE (β = − 0.133, p = 0.561) nor PTE (β = − 0.144; p = 0.505) in predicting DB in girls. Examination of gene-environment correlation (rGE) showed a correlation between paternal MAOA-L and daughters' concurrent stress exposure (r = − 0.240, p = 0.013). Discussion Findings underscore complex mechanisms linking genetic susceptibility and early adverse exposures. Replication in larger cohorts followed from the pregnancy through adolescence is suggested to elucidate mechanisms that appear to have varying developmental expression.