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A novel adapter directing the blood from the inflow of a left ventricular assist device (LVAD) back into the left ventricular apex and across the aortic valve allows LVAD implantation solely via the LV apex, but may affect the LVAD flow rate. We quantified the effect of the adapter on LVAD flow rate in vitro. A mock circulation loop consisting of tubing, two reservoirs (representing left atrium and ventricle) and a resistance valve was established, and sensors for flow rate, pressure (proximal and distal to LVAD) and temperature were implemented. An LVAD (HeartMate 3, Abbott) was attached to the left ventricular reservoir, either with adapter (Adapter) or without adapter (Control). A water/glycerol solution was used as blood substitute. The LVAD was set at three different rotational speeds (4,000/5,200/6,400 rpm). Flow rates were measured at three resistance levels (low/medium/high resistance). Compared to Control, the flow rate in the Adapter group was significantly reduced by an overall average of 0.25 l/min (all speeds, all resistant levels). While the highest flow rate reduction occurred at low resistance levels, the lowest flow rate reduction was seen at high resistance levels (Table). The adapter caused a small reduction of LVAD flow rates that was enhanced by decreases in resistance. Future developments in the adapter design may further reduce this effect and allow both, unimpaired LVAD performance and minimally-invasive device implantation. [ABSTRACT FROM AUTHOR]

In the fabrication of fiber-reinforced plastics materials peel plies are commonly used as an additional layer on top of the laminates to sponge up the surplus resin and to create an activated surface for adhesive bonding or coating by peel ply removal. In theory, the peel ply removal results in a new and uncontaminated fracture surface that is activated by polymer chain scission. The peel ply method is often presented as being a good surface treatment for structural bonding. In this study carbon fiber-reinforced plastics (Hexcel® 8552/ IM7) were produced by the use of five different peel plies and a release foil made of polytetrafluorethylene (PTFE). The peel plies themselves and the surfaces on the CFRP created by peeling were examined by scanning electron microscopy (SEM), x-ray photo electron spectroscopy (XPS), energy-dispersive x-ray spectroscopy (EDX), infrared (IR) spectroscopy, atomic force microscopy (AFM), and contact angle measurements to characterize the surfaces produced. Furthermore, the bond strength of lap shear and floating roller peel samples was determined with and without additional plasma treatment. For bonding, a room temperature-curing two-component-epoxy adhesive (Hysol® 9395) was used to prove the applicability of different peel plies for structural adhesive bonding under repair conditions. [ABSTRACT FROM PUBLISHER]

Immunoglobulin E (IgE) blockade with omalizumab has demonstrated clinical benefit in pruritus-associated dermatoses (e.g. atopic dermatitis, bullous pemphigoid, urticaria). In oncology, pruritus-associated cutaneous adverse events (paCAEs) are frequent with immune checkpoint inhibitors (CPIs) and targeted anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we sought to evaluate the efficacy and safety of IgE blockade with omalizumab in cancer patients with refractory paCAEs related to CPIs and anti-HER2 agents. Patients included in this multicenter retrospective analysis received monthly subcutaneous injections of omalizumab for CPI or anti-HER2 therapy-related grade 2/3 pruritus that was refractory to topical corticosteroids plus at least one additional systemic intervention. To assess clinical response to omalizumab, we used the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was defined as reduction in the severity of paCAEs to grade 1/0. A total of 34 patients (50% female, median age 67.5 years) received omalizumab for cancer therapy-related paCAEs (71% CPIs; 29% anti-HER2). All had solid tumors (29% breast, 29% genitourinary, 15% lung, 26% other), and most (n = 18, 64%) presented with an urticarial phenotype. In total 28 of 34 (82%) patients responded to omalizumab. The proportion of patients receiving oral corticosteroids as supportive treatment for management of paCAEs decreased with IgE blockade, from 50% to 9% (P < 0.001). Ten of 32 (31%) patients had interruption of oncologic therapy due to skin toxicity; four of six (67%) were successfully rechallenged following omalizumab. There were no reports of anaphylaxis or hypersensitivity reactions related to omalizumab. IgE blockade with omalizumab demonstrated clinical efficacy and was well tolerated in cancer patients with pruritus related to CPIs and anti-HER2 therapies. • Omalizumab reduced pruritus related to immune checkpoint inhibitors and anti-HER2 targeted therapies. • IgE blockade resulted in a significantly reduced proportion of patients requiring oral corticosteroids for pruritus. • Omalizumab was safe and tolerable, without report of anaphylaxis or hypersensitivity reactions. [ABSTRACT FROM AUTHOR]

Abstract: Contamination-tolerant adhesives are of ever increasing importance in industrial applications. The possible failure mechanisms of adhesive bonds in these adhesives are however still poorly understood. Results of a series of investigations with our pulsed low energy positron beam system (PLEPS) in an epoxy-based contamination-tolerant adhesive are presented. [Copyright &y& Elsevier]

The LRRK2 G2019S variant is the most common cause of monogenic Parkinson's disease (PD); however, questions remain regarding the penetrance, clinical phenotype and natural history of carriers. We performed a 3.5-year prospective longitudinal online study in a large number of 1286 genotyped LRRK2 G2019S carriers and 109 154 controls, with and without PD, recruited from the 23andMe Research Cohort. We collected self-reported motor and non-motor symptoms every 6 months, as well as demographics, family histories and environmental risk factors. Incident cases of PD (phenoconverters) were identified at follow-up. We determined lifetime risk of PD using accelerated failure time modelling and explored the impact of polygenic risk on penetrance. We also computed the genetic ancestry of all LRRK2 G2019S carriers in the 23andMe database and identified regions of the world where carrier frequencies are highest. We observed that despite a 1 year longer disease duration (P = 0.016), LRRK2 G2019S carriers with PD had similar burden of motor symptoms, yet significantly fewer non-motor symptoms including cognitive difficulties, REM sleep behaviour disorder (RBD) and hyposmia (all P-values ≤ 0.0002). The cumulative incidence of PD in G2019S carriers by age 80 was 49%. G2019S carriers had a 10-fold risk of developing PD versus non-carriers. This rose to a 27-fold risk in G2019S carriers with a PD polygenic risk score in the top 25% versus non-carriers in the bottom 25%. In addition to identifying ancient founding events in people of North African and Ashkenazi descent, our genetic ancestry analyses infer that the G2019S variant was later introduced to Spanish colonial territories in the Americas. Our results suggest LRRK2 G2019S PD appears to be a slowly progressive predominantly motor subtype of PD with a lower prevalence of hyposmia, RBD and cognitive impairment. This suggests that the current prodromal criteria, which are based on idiopathic PD, may lack sensitivity to detect the early phases of LRRK2 PD in G2019S carriers. We show that polygenic burden may contribute to the development of PD in the LRRK2 G2019S carrier population. Collectively, the results should help support screening programmes and candidate enrichment strategies for upcoming trials of LRRK2 inhibitors in early-stage disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

A comprehensive analysis and simulation of two memristor-based neuromorphic architectures for nuclear radiation detection is presented. Both scalable architectures retrofit a locally competitive algorithm to solve overcomplete sparse approximation problems by harnessing memristor crossbar execution of vector-matrix multiplications. The proposed systems demonstrate excellent accuracy and throughput while consuming minimal energy for radionuclide detection. To ensure that the simulation results of our proposed hardware are realistic, the memristor parameters are chosen from our own fabricated memristor devices. Based on these results, we conclude that memristor-based computing is the preeminent technology for a radiation detection platform.

The programmed cell death 1 ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis is primarily associated with immunosuppression in cytotoxic T lymphocytes (CTLs). However, mounting evidence is supporting the thesis that PD-L1 not only functions as a ligand but mediates additional cellular functions in tumor cells. Moreover, it has been demonstrated that PD-L1 is not exclusively localized at the cellular membrane. Subcellular fractionation revealed the presence of PD-L1 in various cellular compartments of six well-characterized head and neck cancer (HNC) cell lines, including the nucleus. Via Western blotting, we detected PD-L1 in its well-known glycosylated/deglycosylated state at 40-55 kDa. In addition, we detected previously unknown PD-L1 variants with a molecular weight at approximately 70 and > 150 kDa exclusively in nuclear protein fractions. These in vitro findings were confirmed with primary tumor samples from head and neck squamous cell carcinoma (HNSCC) patients. Furthermore, we demonstrated that nuclear PD-L1 variant expression is cell-cycle-dependent. Immunofluorescence staining of PD-L1 in different cell cycle phases of synchronized HNC cells supported these observations. Mechanisms of nuclear PD-L1 trafficking remain less understood; however, proximity ligation assays showed a cell-cycle-dependent interaction of the cytoskeletal protein vimentin with PD-L1, whereas vimentin could serve as a potential shuttle for nuclear PD-L1 transportation. Mass spectrometry after PD-L1 co-immunoprecipitation, followed by gene ontology analysis, indicated interaction of nuclear PD-L1 with proteins involved in DNA remodeling and messenger RNA (mRNA) splicing. Our results in HNC cells suggest a highly complex regulation of PD-L1 and multiple tumor cell-intrinsic functions, independent of immune regulation. These observations bear significant implications for the therapeutic efficacy of immune checkpoint inhibition., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Statement of Problem: Three-dimensional (3D) implant planning facilitates determining the optimal position and number of implants, in terms of function and esthetics, by taking into account adjacent structures. Template-guided implant placement is an established procedure for implementing this planning, although the accuracy between the planned and the actual implant position is subject to many influences. The influences of the macrodesign of the implants and the sleeve materials used have rarely been investigated clinically., Purpose: The purpose of this prospective clinical study was to investigate the accuracy of template-guided implant placement according to the macrodesign of different implants and the design of the drill sleeve., Material and Methods: Implants were placed in 60 participants within 3 groups (n=20): tapered implant with a metal sleeve (T-MS), tapered implant with a polymeric sleeve (T-PS), and progressive tapered implant with a polymeric sleeve (XT-PS). After overlaying the 3D implant planning image with the postoperative intraoral scan, deviations were 2-dimensionally related to the implant shoulder (S) and the apex (A) in terms of height (2DHS/2DHA), mesiodistal (2DSmd/2DAmd) and buccolingual (2DSbo/2DAbo), as well as 3-dimensionally on the implant shoulder (3DS), on the apex (3DA), and on the axis deviation (Axis). The groups were compared by using the analysis of variance. The Tukey post hoc test was performed for normally distributed data to identify significant differences among groups (α=.05)., Results: The errors for 2DSmd and 2DSbo were 0.26 to 0.40 mm across all groups. The 3DS group varied between 0.67 and 0.87 mm. No significant differences were found in terms of the material of the sleeves or the macrodesign of the implants (P>.05). Significant differences were found for 2DHS (P=.029) and 2DHA (P=.016) between the groups with the different sleeves. Group T-PS showed the least height deviation., Conclusions: In terms of height deviation, significant differences were found among the groups, with deviations depending on the implant type and the sleeve type. Overall, the method showed a high level of accuracy, providing good predictability of the prosthetic rehabilitation., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Rich in renewable resources, extensive acreage, and bioenergy expertise, Brazil, however, has no established strategies for sustainable aviation fuels, particularly e-kerosene. We extend the lens from the often-studied economic feasibility of individual e-kerosene supply chains to a system-wide perspective. Employing energy system analyses, we examine the integration of e-kerosene production into Brazil's national energy supplies. We introduce PyPSA-Brazil, an open-source energy system optimisation model grounded in public data. This model integrates e-kerosene production and offers granular spatial resolution, enabling federal-level informed decisions on infrastructure locations and enhancing transparency in Brazilian energy supply scenarios. Our findings indicate that incorporating e-kerosene production can bolster system efficiency as Brazil targets a carbon-neutral electricity supply by 2050. The share of e-kerosene in meeting kerosene demand fluctuates between 2.7 and 51.1%, with production costs varying from 113.3 to 227.3 €/MWh. These costs are influenced by factors such as biokerosene costs, carbon pricing, and export aspirations. Our findings are relevant for Brazilian policymakers championing aviation sustainability and offer a framework for other countries envisioning carbon-neutral e-kerosene production and export., (© 2023. The Author(s).)

Gene expression is subject to epigenetic regulation and is dependent upon cellular context. Spatial omics tools can provide insight into cellular context; however, development has centered on spatial transcriptomics and proteomics. Deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) was the first spatial epigenomics platform at the cellular level. Here we present a comparison of spatial epigenomic profiling on both 50-channel and 96-channel platforms. The new 96-channel microfluidics chip design greatly improved precision in cell typing and identification of regulatory elements by spatial-ATAC-seq. Spatial mapping reveals complexity of glial cell and neuronal localization within brain structures as well as cis-regulatory elements controlling cellular function. This technology streamlines spatial analysis of the epigenome and contributes a new layer of spatial omics to uncover the context dependent regulatory mechanisms underpinning development, disease, and normal cellular function.

Background: Chance fracture (CFx) with concomitant intra-abdominal injury has variable occurrence rates ranging from 33 to 89%. No single study has compared the incidence of simultaneous abdominal injury between pediatric and adult populations. This study compares the rate of simultaneous intra-abdominal injury and chance fracture in these populations., Methods: A retrospective review of pediatric and adult patients with chance fracture in comparable pediatric and adult trauma centers was performed. Patient demographics, mechanism of injury (MOI), and injury patterns were collected from 2002 to 2019 for pediatric patients and 2015 to 2018 for adults. Student t-test analyses were performed to determine statistical significance between the cohorts., Results: The pediatric group had a similar incidence of abdominal solid organ injuries compared to adults (16 [20.5%] vs. 40 [19.7%], p<0.879), but the pediatric group had a greater number of total intra-abdominal (49 [62.8%] vs. 47 [23.1%], p < 0.001) and hollow organ injuries (40 [51.3%] vs. 17 [8.4%], p < 0.001). Motor vehicle collision was the most common mechanism of injury for both groups (72 pediatric [92.3%] vs. 85 adult [41.7%]) but adults suffered from more falls (3 pediatric vs. 81 adult, p < 0.001). Pediatric patients with CFx caused by MVCs had more intra-abdominal injuries (48 [66.7%] vs. 25[29.8%], p < 0.001) and hollow organ injuries compared to adults (39 [54.2%] vs. 8[9.5%], p < 0.001)., Conclusion: In the setting of Chance fracture after trauma, pediatric patients are more likely to have a concomitant intra-abdominal organ injury (63% vs. 23%), especially hollow viscus injury (51.3% vs. 8.4%) compared with adults regardless of mechanism.

Definition of MHC class I ligands of rhesus macaque killer cell Ig-like receptors (KIRs) is fundamental to NK cell biology in this species as an animal model for infectious diseases, reproductive biology, and transplantation. To provide a more complete foundation for studying NK cell responses, rhesus macaque KIRs representing common allotypes of lineage II KIR genes were tested for interactions with MHC class I molecules representing diverse Macaca mulatta (Mamu)-A, -B, -E, -F, -I, and -AG alleles. KIR-MHC class I interactions were identified by coincubating reporter cell lines bearing chimeric KIR-CD3ζ receptors with target cells expressing individual MHC class I molecules and were corroborated by staining with KIR IgG-Fc fusion proteins. Ligands for 12 KIRs of previously unknown specificity were identified that fell into three general categories: interactions with multiple Mamu-Bw4 molecules, interactions with Mamu-A-related molecules, including allotypes of Mamu-AG and the hybrid Mamu-B*045:03 molecule, or interactions with Mamu-A1*012:01. Whereas most KIRs found to interact with Mamu-Bw4 are inhibitory, most of the KIRs that interact with Mamu-AG are activating. The KIRs that recognize Mamu-A1*012:01 belong to a phylogenetically distinct group of macaque KIRs with a 3-aa deletion in the D0 domain that is also present in human KIR3DL1/S1 and KIR3DL2. This study more than doubles the number of rhesus macaque KIRs with defined MHC class I ligands and identifies interactions with Mamu-AG, -B*045, and -A1*012. These findings support overlapping, but nonredundant, patterns of ligand recognition that reflect extensive functional diversification of these receptors., (Copyright © 2023 by The American Association of Immunologists, Inc.)

To address the opioid epidemic, some states mandate that prescribers review a state-run prescription drug monitoring program (PDMP) database before prescribing opioids. We used Medicare Part D prescriber data from 2013 (baseline) to 2019 to examine the association between state mandatory-access PDMPs, with and without a cancer exemption, and changes in the percent of oncologists' patients with any opioid fill per year, stratified by oncologists' baseline prescribing volume. Among 9746 medical or hematologic oncologists, the proportion of patients prescribed opioids declined after states implemented mandatory-access PDMPs without a cancer exemption overall (-0.49 percentage point, 95% confidence interval = -0.78 to -0.20 percentage point) and among those with above-median baseline prescribing, but not in states with a cancer exemption (-0.16 percentage point, 95% confidence interval = -0.50 to 0.18 percentage point) or with below-median baseline prescribing. Carefully designed mandatory-access PDMPs with cancer exemptions minimize unnecessary reductions in prescription opioid treatments among oncology patients in need of pain management., (© The Author(s) 2023. Published by Oxford University Press.)

In eusocial insects, offspring survival strongly depends on the quality and quantity of non-breeders. In contrast, the influence of social factors on offspring survival is more variable in cooperatively breeding mammals since maternal traits also play an important role. This difference between cooperative insects and mammals is generally attributed to the difference in the level of sociality. Examining offspring survival in eusocial mammals should, therefore, clarify to what extent social organization and taxonomic differences determine the relative contribution of non-breeders and maternal effects to offspring survival. Here, we present the first in-depth and long-term study on the influence of individual, maternal, social and environmental characteristics on early offspring survival in a eusocial breeding mammal, the naked mole-rat ( Heterocephalus glaber ). Similarly to other mammals, pup birth mass and maternal characteristics such as body mass and the number of mammae significantly affected early pup survival. In this eusocial species, the number of non-breeders had a significant influence on early pup survival, but this influence was negative-potentially an artifact of captivity. By contrasting our findings with known determinants of survival in eusocial insects we contribute to a better understanding of the origin and maintenance of eusociality in mammals.

Background: Restricted weight bearing is commonly prescribed in Legg-Calvé-Perthes Disease (LCPD), raising concerns of causing overweight or obesity. This study utilizes prospectively collected data to address the following questions: (1) does body mass index (BMI) Z-score increase over the course of LCPD follow-up; (2) is having a BMI category of normal, overweight, or obese at baseline associated with BMI Z-score changes over the course of follow-up; and (3) is the duration of weight bearing restrictions (no restrictions, <3, 3 to <6, 6 to 9, or >9 mo) associated with BMI Z-score changes., Methods: Data of 130 children aged 5 to 12 years with unilateral early-stage LCPD were extracted from an international database. Nation-specific BMI Z-scores and percentile-based weight categories were determined, and the duration of follow-up and weight bearing restrictions were calculated. Longitudinal changes in BMI Z-scores were evaluated for the 3 study questions using mixed effects linear regression models with surgery as a covariate. Sensitivity analyses were used to determine the influence of socio-cultural background (USA vs. India) for each study question., Results: During the 35.5±15.9 months of follow-up, no statistically significant increase in BMI Z-scores was observed across the entire cohort, or following stratification by baseline weight categories or the duration of the weight bearing restriction. Sensitivity analyses indicated that patients in the USA had no change in their BMI Z-score. When stratified by weight categories, the normal weight of US children had a small increase in their BMI Z-score (0.005 per mo, 95% confidence interval: 0.0002, 0.009), but this was not seen in other BMI categories. The cohort of Indian children had a small but significant decrease in their BMI Z-score (-0.005/mo, 95% CI: -0.009, -0.0002). After stratification by weight categories, a small decrease of the BMI Z-score was observed only in the Indian overweight children (-0.016 per mo, 95% CI: -0.027, -0.005) and no other BMI category., Conclusions: Weightbearing restrictions over the course of follow-up for our cohort of children with early-stage LCPD were not associated with clinically meaningful increases of BMI Z-scores. Weight gain is multi-factorial and probably not caused by weight bearing restrictions alone., Level of Evidence: III Diagnostic Study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Hematopoietic cell transplantation (HCT) is an established cure for sickle cell disease (SCD) supported by long-term survival, but long-term organ function data are lacking. We sought to describe organ function and assess predictors for dysfunction in a retrospective cohort (n = 247) through the Sickle cell Transplant Advocacy and Research alliance. Patients with <1-year follow-up or graft rejection/second HCT were excluded. Organ function data were collected from last follow-up. Primary measures were organ function, comparing pre- and post-HCT. Bivariable and multivariable analyses were performed for predictors of dysfunction. Median age at HCT was 9.4 years; the majority had HbSS (88.2%) and severe clinical phenotype (65.4%). Most received matched related (76.9%) bone marrow (83.3%) with myeloablative conditioning (MAC; 57.1%). Acute and chronic graft-versus-host disease (GVHD) developed in 24.0% and 24.8%. Thirteen patients (5.3%) died ≥1 year after HCT, primarily from GVHD or infection. More post-HCT patients had low ejection or shortening fractions than pre-HCT (0.6% → 6.0%, P = .007 and 0% → 4.6%, P = .003). The proportion with lung disease remained stable. Eight patients (3.2%) had overt stroke; most had normal (28.3%) or stable (50.3%) brain magnetic resonance imaging. On multivariable analysis, cardiac dysfunction was associated with MAC (odds ratio [OR] = 2.71; 95% confidence interval [CI], 1.09-6.77; P = .033) and severe acute GVHD (OR = 2.41; 95% CI, 1.04-5.62; P = .041). Neurologic events were associated with central nervous system indication (OR = 2.88; 95% CI, 2.00-4.12; P < .001). Overall organ dysfunction was associated with age ≥16 years (OR = 2.26; 95% CI, 1.35-3.78; P = .002) and clinically severe disease (OR = 1.64; 95% CI, 1.02-2.63; P = .043). In conclusion, our results support consideration of HCT at younger age and use of less intense conditioning., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of the study were (1) to compare targeted and routine HIV screening in a pediatric emergency department (PED) and (2) to compare provider documented HIV risk assessment with adolescent perception of HIV risk assessment conducted during the PED visit., Methods: This prospective study ran concurrent to a PED routine HIV screening pilot. Adolescents could be tested for HIV by the PED provider per usual care (targeted testing); if not tested, they were approached for the routine screening pilot. A subset of adolescents completed a questionnaire on HIV risk. χ 2 analysis compared adolescents with targeted testing and routine screening. HIV-tested patients were asked if HIV risk was assessed; κ analysis compared this with documentation in the provider note., Results: Over 4 months, 107 adolescents received targeted testing and 344 received routine screening. One 14-year-old patient tested positive by routine screening; this adolescent had 2 PED visits without targeted testing within 60 days. Compared with routine screening, adolescents with targeted testing were more likely female (82% vs 57%, P < 0.001), 16 years or older (71% vs 44%, P < 0.001), or had genitourinary/gynecologic concerns (48% vs 6%, P < 0.001). Adolescents with HIV risk factors were missed by targeted testing but received routine screening. Adolescents with documented HIV risk assessment were more likely to receive targeted testing. There was moderate agreement (κ = 0.61) between provider documentation and adolescent perception of HIV risk assessment., Conclusions: There are gaps in PED HIV risk assessment and testing, which may miss opportunities to diagnose adolescent HIV. Routine HIV screening addresses these gaps and expands adolescent HIV testing in the PED., Competing Interests: Disclosure: A.C.G. has received funding from Theratechnologies, Inc, for consulting. C.R.M. is the inventor or coinventor of several University of California, San Francisco-Benioff Children's Hospital Oakland patents/patent-pending applications that include nutritional supplements and biomarkers of cardiovascular disease, is an inventor of an Emory University School of Medicine patent application for a nutritional supplement, is a consultant for Pfizer, and has received research support from the US Food and Drug Administration and the National Institutes of Health. The other authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To examine the effects of preoperative gabapentin administration on postoperative pain in pediatric patients undergoing tonsillectomy/adenoidectomy (T/A) in a single ambulatory surgery location within a pediatric healthcare organization., Design: This randomized, controlled pilot study enrolled patients age 3-18 years with American Society of Anesthesiologists (ASA) scores of I-II undergoing T/A., Methods: Both gabapentin and placebo groups were given study medication preoperatively and received standard opiate regimens intraoperatively and postoperative pain instructions. Outcome measurements included: time to first analgesic medication in the postanesthesia care unit (PACU), mean acetaminophen, ibuprofen, and opiate doses in mg/kg. Additionally, we examined pain scores, medication use, and side effects reported by daily pain diaries completed by patients/families for 3 days postoperatively., Findings: Forty-nine patients were included in final analysis (gabapentin n = 26, placebo n = 23). Demographic and clinical characteristics of both groups were similar; the majority (46 of 49) were under the age of 13. Both groups received opiates in PACU. Some patients in both groups received hydrocodone/acetaminophen postoperatively. There were no reported differences in side effects between groups. Gabapentin group reported less use of opiates, acetaminophen, and ibuprofen post-discharge. We identified small effect sizes for opiates and acetaminophen, and medium effect size for ibuprofen (80.1% gabapentin versus 100% placebo, RR 0.81 [95% CI 0.67-0.97]). Median pain scores were 4 on a scale of 10 for both groups for all 3 days of follow-up. Overall median satisfaction score was 9, with a mean difference of 0.35 (95% CI -0.78 - 1.37). Analysis of variance revealed no difference in pain scores or satisfaction per pain diaries between the groups in general and no difference in score trajectory., Conclusions: We were able to establish a rigorous process and feasibility to launch a larger, multi-center trial to examine this important issue. There remain few evidence-based options for acute pain relief in pediatric surgical populations besides opiates . Identifying opiate alternatives that are effective, cost efficient and safe are needed for pediatric tonsillectomy patients., (Copyright © 2021 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

New Jersey's COVID-19 Temporary Emergency Reciprocity Licensure program provided temporary licenses to more than 31,000 out-of-state health care practitioners. As one of the first COVID-19 hot spots in the US, New Jersey is uniquely positioned to provide insights on enabling an out-of-state health care workforce through temporary licensure to address critical, ongoing concerns about health care workforce supply. In January 2021 we surveyed New Jersey temporary licensees. We analyzed more than 10,000 survey responses and found that practitioners who used the temporary license originated from every state in the US, provided both COVID-19- and non-COVID-19-related care, served a combination of new and existing patients, conversed with patients in at least thirty-six languages, and primarily used telehealth. Findings suggest that temporary licensure of out-of-state practitioners, along with telehealth waivers, may be a valuable, short-term solution to mitigating health care workforce shortages during public health emergencies.

Different applications of near-infrared fluorescence-guided surgery are very promising, and techniques that help surgeons in intraoperative guidance have been developed, thereby bridging the gap between preoperative imaging and intraoperative visualization and palpation. Thus, these techniques are advantageous in terms of being faster, safer, less invasive, and cheaper. There are a few fluorescent dyes available, but the most commonly used dye is indocyanine green. It can be used in its natural form, but different nanocapsulated and targeted modifications are possible, making this dye more stable and specific. A new active tumor-targeting strategy is the conjugation of indocyanine green nanoparticles with antibodies, making this dye targeted and highly selective to various tumor proteins. In this mini-review, we discuss the application of near-infrared fluorescence-guided techniques in thoracic surgery. During lung surgery, it can help find small, non-palpable, or additional tumor nodules, it is also useful for finding the sentinel lymph node and identifying the proper intersegmental plane for segmentectomies. Furthermore, it can help visualize the thoracic duct, smaller bullae of the lung, phrenic nerve, or pleural nodules. We summarize current applications and provide a framework for future applications and development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Géczi, Simonka, Lantos, Wetzel, Szabó, Lázár and Furak.)

Aim: We aimed to understand the interplay between retirement pathways and healthcare use in the postponed and structurally changing context of retirement., Methods: Based on Swedish register data on income and healthcare use, we applied combined sequence and cluster analysis to identify typical pathways into retirement and analysed their relation to healthcare use developments., Results: We detected five distinct pathways into retirement. Level of healthcare use was significantly higher for the pathway via disability pensions. We saw an overall increase in healthcare use across the retirement process that was related to age rather than to the different pathways., Conclusions: Level of healthcare use at the beginning of the retirement process may be related to selection into different pathways of retirement. We did not find clear evidence across several healthcare measures that different pathways lead to different developments in healthcare use.

Background: Despite its relevance for healthcare expenditures and public health, few studies have examined how secondary healthcare use changes during the retirement transition. We therefore use Swedish register data to examine whether retirement is associated with intensified secondary healthcare use overall and for specific subgroups based on gender and education., Methods: The sample was all individuals registered in Sweden who retired from paid work in 2010. We used Generalised Estimating Equations models to analyse changes in two indicators of secondary healthcare use, namely specialist visits and hospitalisation, from 3 years prior to 5 years after retirement., Results: Retirement is not associated with changes in specialist visits or hospitalisation per se . Three years before retirement, women were more likely to visit a specialist but less likely to be hospitalised than men; these gender differences disappeared approximately 1 year before retirement. Women with high education were more likely to visit a specialist than women with low education across the entire retirement transition, particularly post-retirement. Significant differences with regard to specialist visits between male educational groups only emerged 12 months after retirement. There were no educational differences with regard to hospitalisation., Conclusions: We conclude that secondary healthcare use in Sweden does not generally change with retirement. However, over the course of retirement gender differences in secondary healthcare use tend to decrease and within-gender educational differences tend to increase. We interpret the results as reflecting the role of labour market institutions in contributing to gender differences but repressing educational differences in secondary healthcare use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wetzel, König and Kelfve.)

Knowledge of the MHC class I ligands of rhesus macaque killer-cell Ig-like receptors (KIRs) is fundamental to understanding the role of natural killer (NK) cells in this species as a nonhuman primate model for infectious diseases, transplantation and reproductive biology. We previously identified Mamu-AG as a ligand for KIR3DL05. Mamu-AG is a nonclassical MHC class I molecule that is expressed at the maternal-fetal interface of the placenta in rhesus macaques similar to HLA-G in humans. Although Mamu-AG and HLA-G share similar molecular features, including limited polymorphism and a short cytoplasmic tail, Mamu-AG is considerably more polymorphic. To determine which allotypes of Mamu-AG serve as ligands for KIR3DL05, we tested reporter cell lines expressing five different alleles of KIR3DL05 (KIR3DL05*001, KIR3DL05*004, KIR3DL05*005, KIR3DL05*008 and KIR3DL05*X) for responses to target cells expressing eight different alleles of Mamu-AG. All five allotypes of KIR3DL05 responded to Mamu-AG2*01:01, two exhibited dominant responses to Mamu-AG1*05:01, and three had low but detectable responses to Mamu-AG3*03:01, -AG3*03:02, -AG3*03:03 and -AG3*03:04. Since KIR3DL05*X is the product of recombination between KIR3DL05 and KIR3DS02 , we also tested an allotype of KIR3DS02 (KIR3DS02*004) and found that this activating KIR also recognizes Mamu-AG2*01:01. Additional analysis of Mamu-AG variants with single amino acid substitutions identified residues in the α1-domain essential for recognition by KIR3DL05. These results reveal variation in KIR3DL05 and KIR3DS02 responses to Mamu-AG and define Mamu-AG polymorphisms that differentially affect KIR recognition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nicholas, Sandstrom, Anderson, Smith, Wetzel, Banerjee, Janaka and Evans.)

Competing Interests: Declaration of Competing Interest Dr. Kiesha Fraser Doh discloses an honorarium received to discuss gun violence for a medical education podcast-Hippo Peds Rap-January 2021. The other authors (EKS, MW, YX, CRM, HKS) have indicated they have no financial relationships relevant to this article to disclose.

While corpus studies have shown that discourse connectives that convey the same coherence relation can display subtle differences, research on online discourse processing has only focused on a rather limited set of connectives. Yet, different connectives - for example, rare or polyfunctional ones - might elicit different reading patterns. In order to explore this assumption, we test the robustness of discourse processing for French native speakers by measuring the way they process causal and concessive sentences that are conveyed by either an appropriate or inappropriate connective. Throughout three experiments, we change important characteristics of the connectives: we first test frequently used connectives (Experiment 1), secondly less frequent ones (Experiment 2), and finally less frequent connectives that are polyfunctional and for which different functions clearly compete (Experiment 3). Our results show that the processing for incoherent items was affected for all connectives, however readers showed altered reading fluency when infrequent connectives were used. We conclude that discourse processing is quite robust and that readers are able to insert meaning conveyed by rare connectives while still showing the highest reading ease with frequent connectives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wetzel, Zufferey and Gygax.)

Background: There is wide variability in the timing of heart transplant (HTx) after pediatric VAD implant. While some centers wait months before listing for HTx, others accept donor heart offers within days of VAD surgery. We sought to determine if HTx within 30 days versus ≥ 30 after VAD impacts post-HTx outcomes., Methods: Children on VAD pre-HTx were extracted from the Pediatric Heart Transplant Study database. The primary endpoints were post-HTx length of hospital stay (LOS) and one-year survival. Confounding was addressed by propensity score weighting using inverse probability of treatment. Propensity scores were calculated based on age, blood type, primary cardiac diagnosis, decade, VAD type, and allosensitization status., Results: A total of 1064 children underwent VAD prior to HTx between 2000 to 2018. Most underwent HTx ≥ 30 days post-VAD (70%). Infants made up 22% of both groups. Patients ≥ 12 years old were 42% of the < 30 days group and children 1 to 11 years comprised 47% of the ≥ 30 days group (p < 0.001). There was no difference in the prevalence of congenital heart disease vs. cardiomyopathy (p = 0.8) or high allosensitization status (p = 0.9) between groups. Post-HTx LOS was similar between groups (p = 0.11). One-year survival was lower in the < 30 days group (adjusted mortality HR 1.76, 95% CI 1.11-2.78, p = 0.016)., Conclusions: A longer duration of VAD support prior to HTx is associated with a one-year survival benefit in children, although questions of patient complexity, post-VAD complications and the impact on causality remain. Additional studies using linked databases to understand these factors will be needed to fully assess the optimal timing for post-VAD HTx., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: High-flow nasal cannula (HFNC) is an oxygen delivery device that provides heated humidified air with higher flow rates. The purpose of this survey is to look at institutional practice patterns of HFNC initiation, weaning, and disposition for pediatric patients across the United States., Methods: Survey was sent via electronic listservs to pediatric physicians in emergency medicine, hospital medicine, critical care, and urgent care. The questionnaire was divided into demographics and HFNC practices (initiation, management, and weaning). One response per institution was included in the analysis., Results: Two hundred twenty-four responses were included in the analysis, composed of 40% pediatric emergency medicine physicians, 46% pediatric hospitalists, 13% pediatric intensive care unit (PICU) physicians, and 1% pediatric urgent care physicians. Ninety-eight percent of the participants have HFNC at their institution. Thirty-seven percent of the respondents had a formal guideline for HFNC initiation. Nearly all guideline and nonguideline institutions report HFNC use in bronchiolitis. Guideline cohort is more likely to have exclusion criteria for HFNC (42% in the guideline cohort vs 17% in the nonguideline cohort; P < 0.001) and less frequently mandates PICU admissions once on HFNC (11% in the guideline cohort vs 56% in the nonguideline cohort; P < 0.001). Forty-six percent of guideline cohort had an objective scoring system to help determine the need for HFNC, and 73% had a weaning guideline., Conclusions: Although there is general agreement to use HFNC in bronchiolitis, great practice variation remains in the initiation, management, and weaning of HFNC across the United States. There is also a discordance on PICU use when a patient is using HFNC., Competing Interests: Disclosure: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The expression of PD-L1 by tumor cells is mainly associated with its immunosuppressive effect. In fact, PD-1/PD-L1 immune checkpoint inhibitors demonstrated remarkable effects in advanced cancer patients including HNSCC. In this context, irradiation is currently being investigated as a synergistic treatment modality to immunotherapy. However, the majority of HNSCC patients still show little improvement or even hyperprogression. Interestingly, there is increasing evidence for additional cell-intrinsic functions of PD-L1 in tumor cells. In previous studies, we showed that PD-L1 has a strong influence on proliferation, migration, invasion, and survival after irradiation. We demonstrated that cellular expression and localization of PD-L1 differed depending on sensitivity to irradiation. Here, we show that PD-L1 is also differentially expressed during cell cycle progression of HNSCC. Furthermore, cellular localization of PD-L1 also changes depending on a particular cell cycle phase. Moreover, distinct observations occurred depending on the general differentiation status. Overall, the function of PD-L1 cannot be generalized. Rather, it depends on the differentiation status and microenvironment. PD-L1 expression and localization are variable, depending on different factors. These findings may provide insight into why differential response to PD-1/PD-L1 antibody therapy can occur. Detailed understanding of cell-intrinsic PD-L1 functions will further allow antibody-based immunotherapy to be optimized.