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Purpose: To identify trends in female pediatric ophthalmologist authorship and representation at the American Academy of Ophthalmology (AAO) Annual Meeting from 2018 to 2022. Methods: Participant data from 2018 to 2022 were collected from the AAO website, organized by conference activity (papers, posters, instruction courses, videos, symposia, subspecialty day, and awards), and analyzed by sex using an online tool. Chi-squared and odds ratio analyses were performed to determine trends in authorship sex and associations between the sex of paper and poster authors in each category. Results: Of 923 pediatric ophthalmology presentations from 2018 to 2022, 46.2% (426 of 923) of presenters and 46.6% (281 of 603) of unique individual participants were women. Overall, 48% (174 of 362) of first and senior authors of papers and posters were women. No significant difference or association between female first and female senior authors was observed (52% vs 44%, P = .14; odds ratio 1.59, P = .13). There was no significant change in the proportion of total female presenters from 2018 to 2019 (−3.09%, P = .53), 2019 to 2020 (0.76%, P = .88), 2020 to 2021 (9.09%, P = .09), 2021 to 2022 (−5.68%, P = .30), or 2018 to 2022 (1.08%, P = .84). Conclusions: Since 2018, female representation at the AAO Annual Meeting has remained consistent and nears 50%. The lack of a significant difference between the proportion of female first and senior authors suggests that junior female pediatric ophthalmologists are climbing the ranks and more broadly engaging in mentorship roles. Considering the increasing proportion of female pediatric ophthalmologists, the absence of corollary, statistically significant increases in female participation may be of concern. [ J Pediatr Ophthalmol Strabismus . 20XX;X(X):XX–XX.]

Purpose: To understand patients' strabismus surgery experience, including its impact on patients' appearance and psychosocial factors such as anxiety and depression, via trends on popular social media platforms. Methods: TikTok and Instagram were searched for the following post hashtags: “#strabismus,” “#strabismussurgery,” “#crosseyed,” and “#lazyeye.” Data regarding date of post, username, gender, city, state, United States or international location, surgical status (preoperative, perioperative, or postoperative), tone (positive or negative), place of treatment, type of post (photo or video), number of likes/views, and number of followers were recorded for statistical analysis. Results: A total of 790 posts (400 TikTok, 390 Instagram) were included. The majority (87.8%) had a positive tone, particularly for Instagram (Instagram = 97.7%, TikTok = 78.3%, P < .01). TikTok had significantly more likes/follower ( P < .01), as did negative posts ( P < .01). #Lazyeye gained significantly more traction than other hashtags (range: P < .001 to .006). There were no differences in likes/follower for treatment phase (preoperative/perioperative/postoperative), gender, or relative age of poster (adult/parent/child). Conclusions: These findings demonstrated that TikTok and Instagram users tend to share positive strabismus surgical experiences; however, negative posts were associated with more interactive responses from viewers. Colloquial hashtags (eg, #lazyeye) were more likely to gain traction than medical terms. TikTok posts were associated with more engagement than Instagram, which suggests TikTok may be a better platform going forward for patient outreach. [ J Pediatr Ophthalmol Strabismus . 20XX;X(X):XX–XX.]

Although originally conceived of as a marriage of direct behavioral observation and indirect behavior rating scales, recent research has indicated that Direct Behavior Ratings (DBRs) are affected by rater idiosyncrasies (rater effects) similar to other indirect forms of behavioral assessment. Most of this research has been conducted using generalizability theory (GT), yet another approach, many-facet Rasch measurement (MFRM), has recently been utilized to illuminate the previously opaque nature of these rater idiosyncrasies. The purpose of this study was to utilize both approaches (GT and MFRM) to consider rater effects with 126 second- through fifth-grade students who were rated on two DBR-Multi-Item Scales by four raters (22 of these ratings were fully crossed). Results indicated the presence of rater effects and revealed nuances about their nature, including showing differences across construct domains, identifying items that are potentially more susceptible to rater effects than others, and isolating specific raters who appear to have been more susceptible to rater effects than other raters. These findings further indicate the indirect nature of DBRs and offer potential avenues for addressing and ameliorating rater effects in research and practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

In pediatric cancer care, medication non-adherence is a significant driver of avoidable suffering and death. There is a lack of interventions designed for families of young children, where patient medication refusal/avoidance is a common barrier to adherence. We developed the

OBJECTIVE To compare the pharmacokinetics between repeated doses and to characterize changes in the fecal microbiome after oral and rectal multidose misoprostol administration. ANIMALS 6 healthy university-owned geldings. PROCEDURES In a randomized, crossover study, misoprostol (5 μg/kg) was administered orally or rectally every 8 hours for 10 doses, or not administered (control), with a 21-day washout between treatments. Concentration-versus-time data for dose 1 and dose 10 were subject to noncompartmental analysis. For microbiota analysis using 16S rRNA amplicon sequencing, manure was collected 7 days before study onset, immediately before dose 1, and 6 hours, 7 days, and 14 days after dose 10, with time-matched points in controls. RESULTS Repeated dosing-related differences in pharmacokinetic parameters were not detected for either administration route. The area under the concentration-versus-time curve was greater (P < .04) after oral versus rectal administration. The relative bioavailability of rectal administration was 4 to 86% of that of oral administration. Microbial composition, richness, and β-diversity differed among subjects (P < .001 all) while only composition differed between treatments (P ≤ .01). Richness was decreased 6 hours after dose 10 and at the control-matched time point (P = .0109) in all subjects. No other differences for time points, treatments, or their interactions were observed. CLINICAL RELEVANCE Differences in systemic exposure were associated with the route of administration but were not detected after repeated administration of misoprostol. Differences in microbiota parameters were primarily associated with interindividual variation and management rather than misoprostol administration.

Background Studies in several fields of medicine have found that women published less during the COVID-19 pandemic, potentially due to an increase in domestic responsibilities. This study examines whether a similar pattern exists for female authorship in ophthalmology. Purpose To compare the proportions of female authorship published in high-impact ophthalmology journals before and during the COVID-19 pandemic. Methods A cross-sectional study analyzing authorship gender of articles published during the COVID-19 pandemic (between July and September 2020) compared with matched articles published in the same journals before the COVID-19 pandemic (between July and September 2019). Gender of the first and last authors was analyzed using an online gender determination tool. Results A total of 577 articles and 1,113 authors were analyzed. There was no significant difference in the average number of publications by male and female authors before and during the COVID-19 pandemic. There was a significant increase in the percentage of female first authorship from the prepandemic period (32%) to during the COVID-19 pandemic (40%; p = 0.01), but no significant increase in the last authorship (p > 0.05). When analyzing only research articles, a similar increase in female first authorship was noted when comparing the publications before (31%) and during the COVID-19 pandemic (43%; p = 0.02). No significant differences were noted when analyzing the editorials (p > 0.05). Conclusion While disparities continue to exist between male and female authorship, an increase in female first authorship was noted during the COVID-19 pandemic for overall articles as well as research articles. Precis During the COVID-19 pandemic, female authorship as first and last authors of peer-reviewed articles in high-impact ophthalmology journals was below 50%. However, while the overall rates of female authorship were unchanged, female first authorship significantly increased during the pandemic. These results differ from studies published in other medical fields that demonstrated a decrease in female authorship during the COVID-19 pandemic.

Cardiovascular disease (CVD) progression occurs across the lifespan. However, available measures of CVD risk in young children are limited. Carotid-femoral pulse wave velocity (cfPWV) is a gold-standard, noninvasive measure of CVD risk that has been studied in children ages 6-18 years. Yet, cfPWV has been measured to a lesser extent in younger children, a population whose temperament or attention span may pose unique challenges. Brachial-femoral PWV (bfPWV) may be feasible, more acceptable, and could provide similar CVD risk assessment to cfPWV in younger children. This study aimed to determine the feasibility of bfPWV measurement in children ages 2-4 years including assessment of comparability of bfPWV to cfPWV normative data.In 10 children (mean 2.9 ± 0.5 years), oscillometric cuffs were placed on the upper thigh and upper arm. Following a 5-min rest, cuffs were inflated to a subdiastolic pressure three times, and waveforms were captured. Procedures were repeated after a 15-min rest. Measured values were compared to age-predicted cfPWV extrapolated from published normative data in children 6-18 years of age.We successfully obtained at least one acceptable quality bfPWV scan in all participants. Among the subset with a repeated measurement ( n = 5), mean (SD) difference between measurements was 0.013 (0.28) m/s. Mean bfPWV was slightly higher than age-predicted cfPWV (observed: 4.55 m/s; predicted: 3.99 m/s; P = 0.012) with larger residuals among younger children and those not reclined in a chair during measurement.bfPWV appears to be feasible tool for noninvasive CVD risk assessment in children ages 2-4 years.

Somatic mutations are a major source of cancer development, and many driver mutations have been identified in protein coding regions. However, the function of mutations located in miRNA and their target binding sites throughout the human genome remains largely unknown. Here, we built detailed cancer-specific miRNA regulatory networks across 30 cancer types to systematically analyze the effect of mutations in miRNAs and their target sites in 3′ untranslated region (3′ UTR), coding sequence (CDS), and 5′ UTR regions. A total of 3,518,261 mutations from 9,819 samples were mapped to miRNA–gene interactions (mGI). Mutations in miRNAs showed a mutually exclusive pattern with mutations in their target genes in almost all cancer types. A linear regression method identified 148 candidate driver mutations that can significantly perturb miRNA regulatory networks. Driver mutations in 3′UTRs played their roles by altering RNA binding energy and the expression of target genes. Finally, mutated driver gene targets in 3′ UTRs were significantly downregulated in cancer and functioned as tumor suppressors during cancer progression, suggesting potential miRNA candidates with significant clinical implications. A user-friendly, open-access web portal (mGI-map) was developed to facilitate further use of this data resource. Together, these results will facilitate novel noncoding biomarker identification and therapeutic drug design targeting the miRNA regulatory networks. Significance: A detailed miRNA–gene interaction map reveals extensive miRNA-mediated gene regulatory networks with mutation-induced perturbations across multiple cancers, serving as a resource for noncoding biomarker discovery and drug development.

Background: Oral chemotherapy nonadherence is a challenge in clinical oncology. During therapy for acute lymphoblastic leukemia (ALL), poor adherence to 6-mercaptopurine (6MP) increases relapse risk. Clinically significant nonadherence is reported in 30% of children treated for ALL on Children's Oncology Group (COG) trials. Whether nonadherence rates vary across regimens with different treatment schedules and modes of administration is unknown. Methods: We conducted an exploratory, cross-sectional survey study on parents of children (1–18 years) receiving continuation therapy on, or as per Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 11-001. Treatment required weekly visits to the clinic and 14 days of oral 6MP every 3 weeks. Survey assessed self-reported sociodemographics, medication-taking, chemotherapy comprehension, and 6MP adherence; adherence survey items were developed from published surveys. Patients were grouped as nonadherent if they endorsed missing one 6MP dose during the last cycle, or more than one dose during prior cycles, for nonmedical reasons. Results: Sixty-two families completed the surveys, all of whom had evaluable adherence data. In total, 25% of patients met the study definition of nonadherence. Twenty-three percent reported that it was “not easy” to follow administration guidelines around the dairy intake and 57% requested more teaching and educational resources. Conclusion: Self-reported nonadherence to oral 6MP in the DFCI ALL Consortium is high, with rates similar to those observed in the COG. This suggests that the additional contact during weekly infusions on the DFCI is insufficient to address barriers affecting oral chemotherapy adherence.

The number of pregnant women with opioid use disorder (OUD) has quadrupled from 1999 to 2014. Current first line treatment for OUD in pregnancy is methadone with increasing support for buprenorphine. Limited data exist on use of buprenorphine/naloxone for OUD in pregnancy despite it being standard therapy in the non-pregnant individuals. The aim of this study was to compare neonatal opioid withdrawal syndrome (NOWS) prevalence and characteristics among neonates born to women prescribed methadone and buprenorphine/naloxone.This is a retrospective cohort analysis of mother-neonate dyads treated with either methadone or buprenorphine/naloxone for OUD in pregnancy who received prenatal care in the substance abuse, treatment, education, and prevention program (STEPP) clinic and delivered at OSU. Primary neonatal outcomes included: neonates diagnosed and treated for NOWS, peak scores on Modified Finnegan Neonatal Abstinence Score (FNAS), number of scores ≥9 on FNAS, and duration of treatment for NOWS. Secondary outcomes included: fetal growth restriction, preterm birth (37 weeks), neonatal head circumference, birth weight, NICU admission, five-minute Apgar score, and length of hospitalization.From 2013 to 2017, we identified 588 mother-neonate dyads: 149 treated with methadone and 439 treated with buprenorphine/naloxone. Ninety-eight neonates (65.8%) in the methadone group were diagnosed with NOWS requiring pharmacological interventions compared with 170 (38.7%) in the buprenorphine/naloxone group (aOR 3.46, 95% confidence interval (CI) 2.31-5.20,Buprenorphine/naloxone treatment for OUD in pregnancy appears safe and has decreased NOWS and pharmacologic intervention for the neonate.

Children’s Oncology Group (COG) trial AHOD0431 reduced systemic therapy and used response-adapted involved-field radiotherapy (IFRT) in early-stage pediatric classic Hodgkin lymphoma. We investigated the impact of positron emission tomographic response after 1 cycle (PET1) and on IFRT outcomes and pattern of relapse. Patients in AHOD0431 underwent PET1 response assessment after AVPC (doxorubicin, vincristine, prednisone, and cyclophosphamide). “Rapid early responders” (RERs) had a negative PET1 (PET1−); “slow early responders” (SERs) had a positive PET1 (PET1+). Patients with a partial response by computed tomographic and functional imaging after 3 chemotherapy cycles received 21-Gy IFRT, whereas complete responders had no IFRT. Progression-free survival (PFS) was evaluated for RERs and SERs treated with or without IFRT. Recurrence sites were initial, new, or both. Relapses involving initial sites were characterized as “within the PET1+ site” or “initially involved but outside the PET1+ site.” Median follow-up was 118 months. The 10-year PFS rate among RERs was 96.6% with IFRT and 84.1% without IFRT (P = .10), whereas SERs were 80.9% with IFRT and 64.0% without IFRT (P = .03). Among 90 RERs who did not receive IFRT, all 14 relapses included an initial site. Among 45 SERs receiving no IFRT, 14 of 16 relapses were in the initial site (9 PET1+ site only). Among 58 patients receiving IFRT, 5 of 10 relapses were in the PET1+ site. After 3 cycles of AVPC alone, RERs showed favorable results. Conversely, SERs had unfavorable outcomes with AVPC alone, although they improved with 21-Gy IFRT. RT remains an important component of treatment for SERs. This trial was registered at www.clinicaltrials.gov as #NCT00302003.

Rabbit hemorrhagic disease virus 2 (RHDV2), a virulent and contagious viral pathogen that affects wild and domestic lagomorph populations, was identified in Wyoming, USA in December 2020. A surveillance program was developed involving full-carcass submission and liver analysis, although carcass quality as a result of predation and decomposition impeded analysis. To increase the number of submissions and provide flexibility to field staff, we evaluated 2 sample types: 77 dried blood on filter paper samples, 66 ear punch samples. At initial sampling, test specificity and sensitivity of the RT-rtPCR utilizing dried blood on filter paper and ear punch samples were both 100% compared to liver. Filter paper results were consistent over time; sensitivity stayed >96% through weeks 2, 4, and 6, with a maximum mean difference of 6.0 Ct from baseline liver Ct values (95% CI: 5.0–7.3) at 6 wk. Test sensitivity of the ear punch sample at 1, 3, 5, and 7 wk post-sampling remained at 100%, with a maximum mean difference of 5.6 Ct from baseline liver Ct values (95% CI: 4.3–6.9) at 5 wk. Filter paper and ear punch samples were suitable alternatives to liver for RHDV2 surveillance in wild lagomorph populations. Alternative sampling options provide more flexibility to surveillance programs, increase testable submissions, and decrease exposure of field personnel to zoonotic disease agents.

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from Multiply-Interacting Massive Particles (MIMPs). Their unique track signature allows a targeted analysis with only 0.05 expected background events from muons. Following unblinding, we observe no signal candidate events. This work places strong constraints on spin-independent interactions of dark matter particles with a mass between 1$\times$10$^{12}\,$GeV/c$^2$ and 2$\times$10$^{17}\,$GeV/c$^2$. In addition, we present the first exclusion limits on spin-dependent MIMP-neutron and MIMP-proton cross-sections for dark matter particles with masses close to the Planck scale., Comment: 7 pages, 6 figures

Xenon dual-phase time projections chambers (TPCs) have proven to be a successful technology in studying physical phenomena that require low-background conditions. With 40t of liquid xenon (LXe) in the TPC baseline design, DARWIN will have a high sensitivity for the detection of particle dark matter, neutrinoless double beta decay ($0\nu\beta\beta$), and axion-like particles (ALPs). Although cosmic muons are a source of background that cannot be entirely eliminated, they may be greatly diminished by placing the detector deep underground. In this study, we used Monte Carlo simulations to model the cosmogenic background expected for the DARWIN observatory at four underground laboratories: Laboratori Nazionali del Gran Sasso (LNGS), Sanford Underground Research Facility (SURF), Laboratoire Souterrain de Modane (LSM) and SNOLAB. We determine the production rates of unstable xenon isotopes and tritium due to muon-included neutron fluxes and muon-induced spallation. These are expected to represent the dominant contributions to cosmogenic backgrounds and thus the most relevant for site selection.

A low-energy electronic recoil calibration of XENON1T, a dual-phase xenon time projection chamber, with an internal $${}^{37}$$ 37 Ar source was performed. This calibration source features a 35-day half-life and provides two mono-energetic lines at 2.82 keV and 0.27 keV. The photon yield and electron yield at 2.82 keV are measured to be ( $$32.3\,\pm \,0.3$$ 32.3 ± 0.3 ) photons/keV and ( $$40.6\,\pm \,0.5$$ 40.6 ± 0.5 ) electrons/keV, respectively, in agreement with other measurements and with NEST predictions. The electron yield at 0.27 keV is also measured and it is ( $$68.0^{+6.3}_{-3.7}$$ 68 . 0 - 3.7 + 6.3 ) electrons/keV. The $${}^{37}$$ 37 Ar calibration confirms that the detector is well-understood in the energy region close to the detection threshold, with the 2.82 keV line reconstructed at ( $$2.83\,\pm \,0.02$$ 2.83 ± 0.02 ) keV, which further validates the model used to interpret the low-energy electronic recoil excess previously reported by XENON1T. The ability to efficiently remove argon with cryogenic distillation after the calibration proves that $${}^{37}$$ 37 Ar can be considered as a regular calibration source for multi-tonne xenon detectors.

We perform a blind search for particle signals in the XENON1T dark matter detector that occur close in time to gravitational wave signals in the LIGO and Virgo observatories. No particle signal is observed in the nuclear recoil, electronic recoil, CE$\nu$NS, and S2-only channels within $\pm$ 500 seconds of observations of the gravitational wave signals GW170104, GW170729, GW170817, GW170818, and GW170823. We use this null result to constrain mono-energetic neutrinos and Beyond Standard Model particles emitted in the closest coalescence GW170817, a binary neutron star merger. We set new upper limits on the fluence (time-integrated flux) of coincident neutrinos down to 17 keV at 90% confidence level. Furthermore, we constrain the product of coincident fluence and cross section of Beyond Standard Model particles to be less than $10^{-29}$ cm$^2$/cm$^2$ in the [5.5-210] keV energy range at 90% confidence level.

Advances in therapies of pediatric acute myeloid leukemia (AML) have been minimal in recent decades. Although 82% of patients will have an initial remission after intensive therapy, approximately 40% will relapse. KMT2A is the most common chromosomal translocation in AML and has a poor prognosis resulting in high relapse rates and low chemotherapy efficacy. Novel targeted approaches are needed to increase sensitivity to chemotherapy. Recent studies have shown how interactions within the bone marrow (BM) microenvironment help AML cells evade chemotherapy and contribute to relapse by promoting leukemic blast survival. This study investigates how DNA hypomethylating agent azacitidine and histone deacetylase inhibitor panobinostat synergistically overcome BM niche-induced chemoprotection modulated by stromal, endothelial, and mesenchymal stem cells and the extracellular matrix (ECM). We show that direct contact between AML cells and BM components mediates chemoprotection. We demonstrate that azacitidine and panobinostat synergistically sensitize MV4;11 cells and KMT2A rearranged pediatric patient-derived xenograft lines to cytarabine in multicell coculture. Treatment with the epigenetic drug combination reduced leukemic cell association with multicell monolayer and ECM in vitro and increased mobilization of leukemic cells from the BM in vivo. Finally, we show that pretreatment with the epigenetic drug combination improves the efficacy of chemotherapy in vivo.

Colonization by Helicobacter pylori is associated with gastric diseases, ranging from superficial gastritis to more severe pathologies, including intestinal metaplasia and adenocarcinoma. The interplay of the host response and the pathogen affect the outcome of disease. One major component of the mucosal response to H. pylori is the activation of a strong but inefficient immune response that fails to control the infection and frequently causes tissue damage. We have shown that polyamines can regulate H. pylori–induced inflammation. Chemical inhibition of ornithine decarboxylase (ODC), which generates the polyamine putrescine from l-ornithine, reduces gastritis in mice and adenocarcinoma incidence in gerbils infected with H. pylori. However, we have also demonstrated that Odc deletion in myeloid cells enhances M1 macrophage activation and gastritis. Here we used a genetic approach to assess the specific role of gastric epithelial ODC during H. pylori infection. Specific deletion of the gene encoding for ODC in gastric epithelial cells reduces gastritis, attenuates epithelial proliferation, alters the metabolome, and downregulates the expression of immune mediators induced by H. pylori. Inhibition of ODC activity or ODC knockdown in human gastric epithelial cells dampens H. pylori–induced NF-κB activation, CXCL8 mRNA expression, and IL-8 production. Chronic inflammation is a major risk factor for the progression to more severe pathologies associated with H. pylori infection, and we now show that epithelial ODC plays an important role in mediating this inflammatory response.

Both human immunodeficiency virus (HIV) infection and alcohol use predispose to autonomic/sensory neuropathy, imbalance symptoms, and cognitive impairment-conditions associated with a greater risk of falls-yet it is unclear how to identify people with HIV (PWH) whose drinking is associated with falls. Research on alcohol and falls using the same instruments in different countries could help to specify the level of alcohol use associated with fall risk. We examined whether a consumption-based measure (the Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]) and/or a symptom-based measure (DSM-5 criteria for alcohol use disorder [AUD]) are associated with sustaining a fall among PWH in St Petersburg, Russia and Boston, Massachusetts in the United States.Separate multivariate logistic regressions were used for each cohort to examine cross-sectional associations for each alcohol measure predicting fall. Potential confounders included physical functioning, depressive symptoms, and other substance use (measured with the Addiction Severity Index).A fall was reported by 35% (87/251) of the sample in Boston and 12% (46/400) in St Petersburg. Each additional AUD criterion-but not higher AUDIT-C score-was significantly associated with a fall in both Boston (odds ratio [OR] = 1.10; 95% confidence interval [CI] 1.02, 1.18) and St Petersburg (adjusted OR AOR = 1.10; 95% CI 1.02, 1.18). Heavy alcohol use (6 drinks/occasion, any vs. none) was associated with more than twice the odds of a fall (AOR = 2.24; 95% CI 1.21, 4.13) in Boston.These findings suggest that while fall risk may vary by setting and population, heavy alcohol use and AUD symptom severity are potential targets for interventions to prevent falls. Studies in diverse global settings advance our understanding of the relationship between alcohol and falls in PWH.

This research monetizes the access benefits of making shared autonomous vehicles (SAVs) available to residents of Texas’ Dallas-Fort Worth metroplex in the U.S. Residents’ willingness to pay for SAV access under different fares and modes was estimated and compared across the region’s 5,386 traffic zones, with emphasis on those housing the regions’ most vulnerable or access-limited travelers. Assuming a $0.50/mi SAV fare, the average per-person-trip benefit is estimated to be $0.64 per trip. With $0.50/mi SAV fare, HV mode share will be reduced from 92.4% to 40.3%, while SAV will take 55.8% of the share. However, if HVs are then disallowed (removed from everyone s mode choice set) after $0.50/mile SAVs have been added, the average net impact is estimated to be −$0.31 per trip, across the metroplex. If HVs were to be replaced by access to SAVs, the impacts are positive, with region-wide average access benefits ranging from $0.16 to $0.33 per trip, depending on the SAV fare, and urban zones have a greater access benefit than rural zones with low SAV fare. Vulnerable populations and their neighborhoods were identified based on the share of persons living below the poverty level, income per capita, share of persons aged 65 years or older, those with disabilities, those owning no vehicle, and share of persons from a racial minority group. Results suggest that the access benefits of SAVs will be higher in locations/neighborhoods housing more vulnerable populations, but some vulnerabilities (e.g., those over age 65) results in lower levels of access improvement. Across those zones with highest shares of vulnerable persons, the range of differences in welfare impacts, from adding SAVs to travelers mode choice sets, widened as fares rose. As is true with many innovations, careful attention to disadvantaged groups and thoughtful policy (via smart contracting and SAV-user subsidies by public agencies, for example) can better ensure valuable access improvements for those with limited mobility and resources.

Mycobacterium abscessusis a nontuberculous mycobacterium emerging as a significant pathogen for individuals with chronic lung disease, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. New strategies of bacterial control based on host defenses are appealing, but anti-mycobacterial immune mechanisms are poorly understood and are complicated by the appearance of smooth and rough morphotypes with distinct host responses. We explored the role of the complement system in the clearance ofM. abscessusmorphotypes by neutrophils, an abundant cell in these infections.M. abscessusopsonized with plasma from healthy individuals promoted greater killing by neutrophils compared to opsonization in heat-inactivated plasma. Rough clinical isolates were more resistant to complement but were still efficiently killed. Complement C3 associated strongly with the smooth morphotype while mannose-binding lectin 2 was associated with the rough morphotype. M. abscessus killing was dependent on C3, but not on C1q or Factor B; furthermore, competition of mannose-binding lectin 2 binding with mannan or N-acetyl-glucosamine during opsonization did not inhibit killing. These data suggest thatM. abscessusdoes not canonically activate complement through the classical, alternative, or lectin pathways. Complement-mediated killing was dependent on IgG and IgM for smooth and on IgG for roughM. abscessus. Both morphotypes were recognized by Complement Receptor 3 (CD11b), but not CR1 (CD35), and in a carbohydrate- and calcium-dependent manner. These data suggest the smooth-to-rough adaptation changes complement recognition ofM. abscessusand that complement is an important factor forM. abscessusinfection.

Tardigrades, commonly known as waterbears, are eight-legged microscopic invertebrates renowned for their ability to withstand extreme stressors, including high osmotic pressure, freezing temperatures, and complete desiccation. Limb retraction and expelling their internal water stores results in the tun state, greatly increasing their ability to survive. Emergence from the tun state and/or activity regain follows stress removal, where resumption of life cycle occurs as if stasis never occurred. However, the mechanism(s) through which tardigrades initiate tun formation is yet to be uncovered. Herein, we use chemobiosis to demonstrate that tardigrade tun formation is mediated by reactive oxygen species (ROS). We further reveal that tuns are dependent on reversible cysteine oxidation, and that this reversible cysteine oxidation is facilitated by the release of intracellular reactive oxygen species (ROS). We provide the first empirical evidence of chemobiosis and map the initiation and survival of tardigrades via osmobiosis, chemobiosis, and cryobiosis. In vivo electron paramagnetic spectrometry suggests an intracellular release of reactive oxygen species following stress induction; when this release is quenched through the application of exogenous antioxidants, the tardigrades can no longer survive osmotic stress. Together, this work suggests a conserved dependence of reversible cysteine oxidation across distinct tardigrade cryptobioses.

Aims: Aerobic exercise typically enhances endurance across vertebrates so that chronically high energy demands can be met. Some known mechanisms of doing this include increases in red blood cell numbers, angiogenesis, muscle fiber adaptions, mitochondria biogenesis, and changes to cellular metabolism and oxidative phosphorylation. We used green anole lizards (Anolis carolinensis) to test for an effect of aerobic exercise on metabolism, mitochondria densities, and mitochondrial function.Methods: We first tested the response of green anoles to endurance training and pyrroloquinoline quinone (PQQ) supplementation, which has been shown to increase mitochondria biogenesis. We also conducted a mitochondrial stress test to determine how training affected mitochondrial function in skeletal muscle fibers. Results: Aerobic exercise led to increased endurance and decreased standard metabolic rate (SMR), while PQQ did not affect endurance and increased SMR. In a second experiment, aerobic exercise increased endurance and decreased resting metabolic rate (RMR) in both male and female green anoles. Higher counts of mitochondrial gene copies in trained lizards suggested additional mitochondria adaptations to achieve increased endurance and decreased metabolism. A mitochondrial stress test revealed no effect on baseline oxygen consumption rates of muscle fibers, but untrained lizards had higher maximal oxygen consumption rates with the addition of metabolic fuel.Conclusion: It is likely that trained lizards exhibited lower maximal oxygen consumption rates by developing higher mitochondria efficiency. This adaptation allows for high ATP demand to be met by making more ATP per oxygen molecule consumed. On the other hand, it is possible that untrained lizards prioritized limiting reactive oxygen species (ROS) production at rest, while sacrificing higher levels of proton leak and higher oxygen consumption rates when working to meet high ATP demand.

Background There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions. Methods Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications. Results Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection. Conclusions Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes. Trial registration clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1.

The penetration of biofilms by antimicrobials is a potential limiting factor in biofilm control. This is relevant to oral health, where compounds used to control microbial growth and activities could also affect the permeability of dental plaque biofilm with secondary effects on biofilm tolerance. We have investigated the effects of zinc salts on the permeability of Streptococcus mutans biofilms. Biofilms were grown with low concentrations of zinc acetate-(ZA) and a transwell transportation assay was applied to test biofilm permeability in an apical-basolateral direction. Crystal violet assays and total viable counts were used to quantify biofilm formation and viability, respectively, and short timeframe diffusion rates within microcolonies were determined using spatial Intensity Distribution Analysis (SpIDA). Whilst diffusion rates within biofilm microcolonies were not significantly altered, exposure to ZA significantly increased the overall permeability of S. mutans biofilms (p

BackgroundCognitive dysfunction and communication impairment are common and disabling symptoms in Parkinson’s Disease (PD). Action verb deficits occur in PD, but it remains unclear if these impairments are related to motor system dysfunction and/or cognitive decline. The objective of our study was to evaluate relative contributions of cognitive and motor dysfunction to action verb production in naturalistic speech of patients with PD. We proposed that pausing before action-related language is associated with cognitive dysfunction and may serve as a marker of mild cognitive impairment in PD.MethodParticipants with PD (n = 92) were asked to describe the Cookie Theft picture. Speech files were transcribed, segmented into utterances, and verbs classified as action or non-action (auxiliary). We measured silent pauses before verbs and before utterances containing verbs of different classes. Cognitive assessment included Montreal Cognitive Assessment (MoCA) and neuropsychological tests to categorize PD participants as normal cognition (PD-NC) or mild cognitive impairment (PD-MCI) based on Movement Disorders Society (MDS) Task Force Tier II criteria. Motor symptoms were assessed using MDS-UPDRS. We performed Wilcoxon rank sum tests to identify differences in pausing between PD-NC and PD-MCI. Logistic regression models using PD-MCI as dependent variables were used to evaluate the association between pause variables and cognitive status.ResultsParticipants with PD-MCI demonstrated more pausing before and within utterances compared to PD-NC, and the duration of these pauses were correlated with MoCA but not motor severity (MDS-UPDRS). Logistic regression models demonstrated that pauses before action utterances were associated with PD-MCI status, whereas pauses before non-action utterances were not significantly associated with cognitive diagnosis.ConclusionWe characterized pausing patterns in spontaneous speech in PD-MCI, including analysis of pause location with respect to verb class. We identified associations between cognitive status and pausing before utterances containing action verbs. Evaluation of verb-related pauses may be developed into a potentially powerful speech marker tool to detect early cognitive decline in PD and better understand linguistic dysfunction in PD.

We developed a detector signal characterization model based on a Bayesian network trained on the waveform attributes generated by a dual-phase xenon time projection chamber. By performing inference on the model, we produced a quantitative metric of signal characterization and demonstrate that this metric can be used to determine whether a detector signal is sourced from a scintillation or an ionization process. We describe the method and its performance on electronic-recoil (ER) data taken during the first science run of the XENONnT dark matter experiment. We demonstrate the first use of a Bayesian network in a waveform-based analysis of detector signals. This method resulted in a 3% increase in ER event selection efficiency with a simultaneously effective rejection of events outside of the region of interest. The findings of this analysis are consistent with the previous analysis from XENONnT, namely a background-only fit of the ER data., 10 pages, 6 figures