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Environment-assisted cracking (EAC) is a pertinent failure mode for many applications and industries, but the design of robust EAC mitigation strategies can be challenging due to the number of material and environmental factors that affect EAC behavior. In this study, a coupled experimental-modeling approach for designing EAC mitigation strategies in a standard panel-and-fastener geometry is presented. Fracture mechanics-based testing is executed on a high-performance steel (Pyrowear 675) immersed in 0.6 M NaCl to assess the effect of electrode potential and loading rate on EAC susceptibility. Finite element modeling (FEM) is then used to calculate the electrode potential distribution across the panel for four realistic EAC mitigation strategies (anodized fastener, fully coated panel, selectively coated panel, and bare panel/fastener). The FEM and EAC susceptibility data are synthesized to inform the efficacy of each proposed mitigation strategy. Results demonstrate that the anodized fastener and fully coated panel approaches are likely to promote EAC, while the selectively coated panel and all-bare strategies mitigate EAC. The benefits and limitations of this coupled approach for mitigating EAC are then discussed.

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.

In this paper, the authors create, justify, and document a system dynamics model of the oil and gas production within the Permian Basin of Texas. Then the researchers show how to fit the model to historical time series data (big data). The authors use the model to better understand the process structure, the production dynamics, and to explore the deleterious consequences of limited pipeline capacity in the Permian Basin. The model is also employed to better understand how to increase revenues derived from the basin. From this model, numerous suggestions are made as to how to improve the overall revenue and profitability coming from the Permian Basin. The model's ultimate purposes and its associated big data are to foster a basic appreciation of the causality inherent in the ‘system' and how basic model parameters affect and influence measures of model performance.

As a high-strength corrosion-resistant alloy, stress corrosion cracking (SCC) behavior is a key consideration for the conventional, wrought form of 17-4PH stainless steel. With the increasing popularity of the additively manufactured (AM) form of 17-4PH, understanding the SCC behavior of AM 17-4PH will be similarly critical for its presumed, future applications. The current study quantifies and compares the SCC behavior of both the wrought form, as a baseline, and AM form of 17-4PH at peak-aged (∼1,200 MPa) and overaged (∼1,050 MPa) strength levels. The laser powder bed fusion technique followed by post-process hot isostatic press (HIP), solution annealing, and aging heat treatments is used to produce AM 17-4PH with similar microstructures and strength levels to wrought 17-4PH and facilitate the comparison. SCC behavior is quantified using fracture mechanics-based rising (dK/dt = 2 MPa√m/h) and constant (dK/dt = 0 MPa√m/h) stress intensity tests in neutral 0.6 M NaCl at various applied potentials. Limited SCC susceptibility was observed at open-circuit and anodic potentials for both forms of 17-4PH. At cathodic applied potentials, AM consistently underperforms wrought with up to 5-fold faster crack growth rates and 200 mV to 400 mV wider SCC susceptibility ranges. These results are interrogated through microstructural and fractographic analysis and interpreted through a decohesion-based hydrogen-assisted crack model. Initial analyses show that (1) increased oxygen content, (2) porosity induced by argon processing, and (3) slow cooling (310°C/h) during conventional HIP processing might contribute to degraded SCC performance in AM 17-4PH.

Introduction: Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse. Methods: We conducted a cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of 2, chronic dialysis, or having received a kidney transplant). The secondary outcomes included renal impairment (eGFR 2), albuminuria (albumin-to-creatinine ratio [ACR] >30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes. Results: A total of 2864 participants (mean age 48.1 [SD 10.3], 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio [OR] 10.58, 95% CI 6.22–17.99), renal impairment (OR 5.50, 95% CI 3.81–7.95), albuminuria (OR 3.34, 95% CI 2.00–5.56), and HIVAN (OR 30.16, 95% CI 12.48–72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes. Conclusion: APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort.

Aluminum components used in aerospace structures are commonly coupled with stainless steel fasteners. These through-hole geometries on the aluminum substrate cause a concentrated stress field. The high-stresses at the fastener sites can preferentially initiate coating damage allowing for moisture ingress, which can lead to the formation of a galvanic couple between the aluminum alloy and the stainless steel fastener. Corrosion damage is known to cause early initiation of fatigue cracks, thus severely reducing the total life of the component. This work aims to understand the relative impact and interaction of fastener hole geometry-induced stress concentrations and corrosion damage on the fatigue crack initiation behavior and total fatigue life. Specifically, by imparting various levels of corrosion severities at different locations within the macro-scale stress field, the relative impact of each on the fatigue process can be determined. This work demonstrated a dominant role of the macro-scale stress field on the ability of corrosion morphologies to initiate fatigue cracks. Specifically, crack formation was found to preferentially occur at high-stress regions in lieu of forming at lower-stress regions, regardless of corrosion severity, and corrosion severity in the through-hole had a significant, but nonpredictive, correlation with the total fatigue life. Critically, the findings of this work will inform the means by which coatings are evaluated and will serve as a controlled validation of experiments for fracture mechanics modeling.

The Bering Land Bridge connecting North America and Eurasia was periodically exposed and inundated by oscillating sea levels during the Pleistocene glacial cycles. This land connection allowed the intermittent dispersal of animals, including humans, between Western Beringia (far north-east Asia) and Eastern Beringia (north-west North America), changing the faunal community composition of both continents. The Pleistocene glacial cycles also had profound impacts on temperature, precipitation, and vegetation, impacting faunal community structure and demography. While these palaeoenvironmental impacts have been studied in many large herbivores from Beringia (e.g., bison, mammoths, horses), the Pleistocene population dynamics of the diverse guild of carnivorans present in the region are less well understood, due to their lower abundances. In this study, we analyse mitochondrial genome data from ancient brown bears (Ursus arctos; n = 103) and lions (Panthera spp.; n = 39), two megafaunal carnivorans that dispersed into North America during the Pleistocene. Our results reveal striking synchronicity in the population dynamics of Beringian lions and brown bears, with multiple waves of dispersal across the Bering Land Bridge coinciding with glacial periods of low sea levels, as well as synchronous local extinctions in Eastern Beringia during Marine Isotope Stage 3. The evolutionary histories of these two taxa underscore the crucial biogeographic role of the Bering Land Bridge in the distribution, turnover, and maintenance of megafaunal populations in North America.

This research, conducted at a midsize university, focused on the virtue of tolerance as it relates to an often-neglected area of diversity—diversity of conscience—defined as ‘legitimate differences...

Presbyters served as individual pastors for rural congregations or at a regional church in the city of Carthage or another city, such as Sufetula, that had multiple churches and congregations. Twenty such presbyters can be identified by name or location. A presbyter or group of presbyters also might serve as a substitute for a bishop who was travelling, disabled, or between the death of one bishop and consecration of a successor. One such presbyter (Heraclius of Hippo) can be identified as long-term administrator for Augustine. Augustine’s correspondence and the legislation of the African bishops—usually on disciplinary issues—provides most of the information about presbyters serving as pastors. The legislation of the African church restricted the authority of these presbyters to baptize and to perform other actions that changed the status of a member of the congregation: admit penitents to communion apart from emergencies, to consecrate virgins. Although the legislation referred to the presbyter as praepositus, the person placed in charge, presbyteral pastors acted under the supervision of the bishop.

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.

Uniaxial tensile experiments on hydrogen-charged and non-charged polycrystalline nickel deformed to a true plastic strain of ~0.1 at room temperature and 77 K reveal that hydrogen has no measurable effect on texture evolution. Texture measurements were completed on samples of each condition, as well as an as-received reference specimen, using electron backscatter diffraction data collected from >20,000 individual grains. Crystal plasticity simulations support the conclusion that the similarity is attributable to the insensitivity of small-strain deformation texture evolution to potential hydrogen-induced modifications in deformation mechanisms.