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The snow crab (Chionoecetes opilio) fishery off the east coast of Newfoundland and Labrador, Canada, has been impacted by annual seismic oil and gas surveying in recent decades, and commercial crab harvesters are concerned that it could potentially affect this resource. A laboratory study was performed to investigate the effects of chronic noise exposure on the transcriptomes of snow crab hemocytes and hepatopancreas, which are important in immunity, metabolism and response to environmental stress. Snow crab were held in replicate control or experimental tanks; on alternating days, the experimental tanks were exposed to noise from an underwater speaker which played a recording of a seismic airgun firing every 10 sec in a continuous loop for ~ 22 weeks (chronic noise). RNA sequencing was used to identify candidate noise-responsive molecular biomarkers in both hemocytes and hepatopancreas. The quantified transcripts of individuals (i.e. n=10 from each of the four groups) were compared using DESeq2, identifying over 300 noise-responsive transcripts in each cell/tissue type. Real-time quantitative polymerase chain reaction (qPCR) assays were designed and run for 61 of these transcripts with significant BLASTx hits. One transcript (rgs2) was significantly (p < 0.05) higher expressed in both hemocytes and hepatopancreas in response to noise; five and seven other transcripts were either significant or showed a non-significant trend of differential expression (0.05 < p ≤ 0.1) in hemocytes (e.g. cfb upregulated, sacs and myof downregulated) and hepatopancreas (e.g. gpx3 and atf3 upregulated, sult1c4 downregulated), respectively. To further investigate the performance and utility of these candidate biomarkers in the field, expression levels of 25 selected transcripts were then examined in the hepatopancreas of snow crab that had been subjected to 2D and 3D seismic surveying using both qPCR and multivariate statistical analyses. Overall, few of these biomarkers showed consistent results in field-collected snow crab, highlighting the need to combine lab and field-based studies to fully evaluate the utility of biomarkers. Nonetheless, our study still identified noise-responsive biomarkers in both settings (including stress and immune relevant genes), providing valuable information for understanding the impact of ocean noise on snow crab physiology and health.

Summary: Synaptic plasticity is hypothesized to underlie “replay” of salient experience during hippocampal sharp-wave/ripple (SWR)-based ensemble activity and to facilitate systems-level memory consolidation coordinated by SWRs and cortical sleep spindles. It remains unclear how molecular changes at synapses contribute to experience-induced modification of network function. The synaptic protein KIBRA regulates plasticity and memory. To determine the impact of KIBRA-regulated plasticity on circuit dynamics, we recorded in vivo neural activity from wild-type (WT) mice and littermates lacking KIBRA and examined circuit function before, during, and after novel experience. In WT mice, experience altered population activity and oscillatory dynamics in a manner consistent with incorporation of new information content in replay and enhanced hippocampal-cortical communication. While baseline SWR features were normal in KIBRA conditional knockout (cKO) mice, experience-dependent alterations in SWRs were absent. Furthermore, intra-hippocampal and hippocampal-cortical communication during SWRs was disrupted following KIBRA deletion. These results indicate molecular mechanisms that underlie network-level adaptations to experience.

Ulnar collateral ligament (UCL) reconstruction of the medial elbow is considered to be the gold standard for treating valgus instability seen in overhead throwing athletes. The first UCL construction was performed by Frank Jobe in 1974, and this procedure has evolved over time to include multiple techniques that improved the biomechanical strength of the graft fixation and maximize the rate of return to athletic competition for these patients. The most common UCL-reconstruction technique used today is the docking technique. The purpose of this Technical Note is to describe our technique, including pearls and pitfalls, which combines the many advantages of the docking technique with a proximal single-tunnel suspensory fixation technique. This method allows for optimal tensioning of the graft, allowing for secure fixation that relies on metal implants as opposed to tying sutures over a proximal bone bridge.

Introduction: Despite progress in whole-organ decellularization and recellularization, maintaining long-term perfusion in vivo remains a hurdle to realizing clinical translation of bioengineered kidney grafts. The objectives for the present study were to define a threshold glucose consumption rate (GCR) that could be used to predict in vivo graft hemocompatibility and utilize this threshold to assess the in vivo performance of clinically relevant decellularized porcine kidney grafts recellularized with human umbilical vein endothelial cells (HUVECs).Materials and methods: Twenty-two porcine kidneys were decellularized and 19 were re-endothelialized using HUVECs. Functional revascularization of control decellularized (n = 3) and re-endothelialized porcine kidneys (n = 16) was tested using an ex vivo porcine blood flow model to define an appropriate metabolic glucose consumption rate (GCR) threshold above which would sustain patent blood flow. Re-endothelialized grafts (n = 9) were then transplanted into immunosuppressed pigs with perfusion measured using angiography post-implant and on days 3 and 7 with 3 native kidneys used as controls. Patent recellularized kidney grafts underwent histological analysis following explant.Results: The glucose consumption rate of recellularized kidney grafts reached a peak of 39.9 ± 9.7 mg/h at 21 ± 5 days, at which point the grafts were determined to have sufficient histological vascular coverage with endothelial cells. Based on these results, a minimum glucose consumption rate threshold of 20 mg/h was set. The revascularized kidneys had a mean perfusion percentage of 87.7% ± 10.3%, 80.9% ± 33.1%, and 68.5% ± 38.6% post-reperfusion on Days 0, 3 and 7, respectively. The 3 native kidneys had a mean post-perfusion percentage of 98.4% ± 1.6%. These results were not statistically significant.Conclusion: This study is the first to demonstrate that human-scale bioengineered porcine kidney grafts developed via perfusion decellularization and subsequent re-endothelialization using HUVEC can maintain patency with consistent blood flow for up to 7 days in vivo. These results lay the foundation for future research to produce human-scale recellularized kidney grafts for transplantation.

BackgroundPregnancy is known to induce extensive biological changes in the healthy mother. Little is known, however, about what these changes are at the molecular level. We have examined systemic expression changes in protein-coding genes and long non-coding (lnc) RNAs during and after pregnancy, compared to before pregnancy, among healthy women with term pregnancies.MethodsBlood samples were collected from 14 healthy women enrolled in our prospective pregnancy cohort at 7 time-points (before, during and after pregnancy). Total RNA from frozen whole blood was used for RNA sequencing. Following raw read alignment and assembly, gene-level counts were obtained for protein-coding genes and long non-coding RNAs. At each time-point, cell type proportions were estimated using deconvolution. To examine associations between pregnancy status and gene expression over time, Generalized Estimating Equation (GEE) models were fitted, adjusting for age at conception, and with and without adjusting for changes in cell type proportions. Fold-changes in expression at each trimester were examined relative to the pre-pregnancy baseline.ResultsNumerous immune-related genes demonstrated pregnancy-associated expression, in a time-dependent manner. The genes that demonstrated the largest changes in expression included several that were neutrophil-related (over-expressed) and numerous immunoglobulin genes (under-expressed). Estimated cell proportions revealed a marked increase in neutrophils, and less so of activated CD4 memory T cells, during pregnancy, while most other cell type proportions decreased or remained unchanged. Adjusting for cell type proportions in our model revealed that although most of the expression changes were due to changes in cell type proportions in the bloodstream, transcriptional regulation was also involved, especially in down-regulating expression of type I interferon inducible genes.ConclusionCompared to a pre-pregnancy baseline, there were extensive systemic changes in cell type proportions, gene expression and biological pathways associated with different stages of pregnancy and postpartum among healthy women. Some were due to changes in cell type proportions and some due to gene regulation. In addition to providing insight into term pregnancy among healthy women, these findings also provide a “normal” reference for abnormal pregnancies and for autoimmune diseases that improve or worsen during pregnancy, to assess deviations from normal.

Background: Previous research has demonstrated disparities in surgical management of diverticulitis based on various patient characteristics, including race. Recent investigation suggests environmental factors may also play a prominent role in patient outcomes. The Center for Disease Control and Prevention's Social Vulnerability Index (SVI) is emerging as a useful tool for studying this effect and may better characterize social determinants of health among colorectal pathology. Methods: This was a retrospective review of patients in the Healthcare Cost and Utilization Project Florida State Inpatient Database (2006–2014), matched by ZIP code to their corresponding SVI. Patients admitted through the emergency department with a primary diagnosis of diverticulitis were included. The rate of stoma creation amongst patients undergoing non-elective surgery for uncomplicated diverticulitis was compared by SVI. Results: Of the 4,212 patients in this study who underwent colectomy, 2,310 (54.8%) received a stoma. Compared to those with low vulnerability, highly vulnerable patients were more likely to receive a stoma (p = 0.014). In multivariable logistic analysis, increasing vulnerability was independently associated with increased odds of stoma creation (OR 1.08, p

Ecoacoustic monitoring has proliferated as autonomous recording units (ARU) have become more accessible. ARUs provide a non-invasive, passive method to assess ecosystem dynamics related to vocalizing animal behavior and human activity. With the ever-increasing volume of acoustic data, the field has grappled with summarizing ecologically meaningful patterns in recordings. Almost 70 acoustic indices have been developed that offer summarized measurements of bioacoustic activity and ecosystem conditions. However, their systematic relationships to ecologically meaningful patterns in varying sonic conditions are inconsistent and lead to non-trivial interpretations. We used an acoustic dataset of over 725,000 min of recordings across 1,195 sites in Sonoma County, California, to evaluate the relationship between 15 established acoustic indices and sonic conditions summarized using five soundscape components classified using a convolutional neural network: anthropophony (anthropogenic sounds), biophony (biotic sounds), geophony (wind and rain), quiet (lack of emergent sound), and interference (ARU feedback). We used generalized additive models to assess acoustic indices and biophony as ecoacoustic indicators of avian diversity. Models that included soundscape components explained acoustic indices with varying degrees of performance (avg. adj-R2 = 0.61 ± 0.16; n = 1,195). For example, we found the normalized difference soundscape index was the most sensitive index to biophony while being less influenced by ambient sound. However, all indices were affected by non-biotic sound sources to varying degrees. We found that biophony and acoustic indices combined were highly predictive in modeling bird species richness (deviance = 65.8%; RMSE = 3.9 species; n = 1,185 sites) for targeted, morning-only recording periods. Our analyses demonstrate the confounding effects of non-biotic soundscape components on acoustic indices, and we recommend that applications be based on anticipated sonic environments. For instance, in the presence of extensive rain and wind, we suggest using an index minimally affected by geophony. Furthermore, we provide evidence that a measure of biodiversity (bird species richness) is related to the aggregate biotic acoustic activity (biophony). This established relationship adds to recent work that identifies biophony as a reliable and generalizable ecoacoustic measure of biodiversity.

Cell migration plays an essential role in physiological and pathological states, such as immune response, tissue generation and tumor development. This phenomenon can occur spontaneously or it can be triggered by an external stimuli, including biochemical, mechanical, or electrical cues that induce or direct cells to migrate. The migratory response to these cues is foundational to several fields including neuroscience, cancer and regenerative medicine. Various platforms are available to qualitatively and quantitatively measure cell migration, making the measurements of cell motility straight-forward. Migratory behavior must be analyzed by multiple metrics and then models to connect the measurements to physiological meaning. This review will focus on describing and quantifying cell movement for individual cell migration.

Burns and their subsequent contracture result in devastating functional and aesthetic consequences which disproportionally affect the upper extremity. By focusing on reconstruction with analogous tissue and utilizing the reconstructive elevator, function can be restored concomitantly with form and aesthetic appearance. General concepts for soft-tissue reconstruction after burn contracture are presented for different sub-units and joints.

Background:. The purpose of this study was to evaluate opioid demand after open reduction and internal fixation of distal radius fractures in patients with and without a diagnosis of cannabis use. Methods:. The PearlDiver database was queried for all patients who underwent open reduction and internal fixation of distal radius fractures between 2010 and 2020. Patients were categorized into two groups: (1) those with an active diagnosis of cannabis use (case) and (2) those without (control). The primary outcome measure was morphine milligram equivalents per prescription filled within 30 days after surgery. A logistic regression was used to determine potential risk factors associated with increased opioid filling patterns. Results:. The rates of prescription refills before and after surgery were congruent in both the case and control populations and did not show significant differences (P > 0.05). The average morphine milligram equivalents of patients’ first opioid prescription was significantly reduced in the case population compared with the control (352.26 versus 480.61 morphine milligram equivalents/prescription, P = 0.005). A history of chronic opioid use was the strongest predictor of prolonged opioid prescription refills after surgery. Conclusions:. This study found a significant reduction in opioid volume in patients with a diagnosis of cannabis use who filled an opioid prescription after open reduction and internal fixation of distal radius fractures. Mental health diagnoses, specifically depression, showed an increased risk of multiple opioid prescription refills in patients without a diagnosis of cannabis use.

The clinical usefulness MRI biomarkers for aging and dementia studies relies on precise brain morphological measurements; however, scanner and/or protocol variations may introduce noise or bias. One approach to address this is post-acquisition scan harmonization. In this work, we evaluate deep learning (neural style transfer, CycleGAN and CGAN), histogram matching, and statistical (ComBat and LongComBat) methods. Participants who had been scanned on both GE and Siemens scanners (cross-sectional participants, known as Crossover (n = 113), and longitudinally scanned participants on both scanners (n = 454)) were used. The goal was to match GE MPRAGE (T1-weighted) scans to Siemens improved resolution MPRAGE scans. Harmonization was performed on raw native and preprocessed (resampled, affine transformed to template space) scans. Cortical thicknesses were measured using FreeSurfer (v.7.1.1). Distributions were checked using Kolmogorov-Smirnov tests. Intra-class correlation (ICC) was used to assess the degree of agreement in the Crossover datasets and annualized percent change in cortical thickness was calculated to evaluate the Longitudinal datasets. Prior to harmonization, the least agreement was found at the frontal pole (ICC = 0.72) for the raw native scans, and at caudal anterior cingulate (0.76) and frontal pole (0.54) for the preprocessed scans. Harmonization with NST, CycleGAN, and HM improved the ICCs of the preprocessed scans at the caudal anterior cingulate (>0.81) and frontal poles (>0.67). In the Longitudinal raw native scans, over- and under-estimations of cortical thickness were observed due to the changing of the scanners. ComBat matched the cortical thickness distributions throughout but was not able to increase the ICCs or remove the effects of scanner changeover in the Longitudinal datasets. CycleGAN and NST performed slightly better to address the cortical thickness variations between scanner change. However, none of the methods succeeded in harmonizing the Longitudinal dataset. CGAN was the worst performer for both datasets. In conclusion, the performance of the methods was overall similar and region dependent. Future research is needed to improve the existing approaches since none of them outperformed each other in terms of harmonizing the datasets at all ROIs. The findings of this study establish framework for future research into the scan harmonization problem.

Introduction: Human behavior and understanding of the vaccine ecosystem play a critical role in the vaccination decision-making process. The objective of this study was to understand different cognitive biases that may lead to vaccine acceptance or hesitancy. Methods: The eligibility criteria for this scoping review was vaccination-related cognitive bias studies published in the English language from inception to April 2022 and available on PubMed, Embase, and Google Scholar. It included all geographical locations and individuals of all age groups and excluded studies focusing on (i) clinical trials of vaccines, (ii) vaccine research conduct bias, (iii) cognitive delay, or (iv) statistical biases. The search method also included reviewing references in the retrieved articles. Results: Overall, 58 articles were identified, and after screening, 19 were included in this study. Twenty-one cognitive biases with the potential to affect vaccination decision-making were observed. These biases were further grouped into three broad categories: cognitive biases seen while processing vaccine-related information, during vaccination-related decision-making, and due to prior beliefs regarding vaccination. Conclusions: This review identified critical cognitive biases affecting the entire process of vaccination that can influence research and public health efforts both positively and negatively. Recognizing and mitigating these cognitive biases is crucial for maintaining the population’s level of trust in vaccination programs around the world.

Poor baseline reaction time, as measured via the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT), has been associated with anterior cruciate ligament (ACL) injury risk in adult athletes. Our study sought to determine whether the reaction time and impulse control ImPACT test domains differed between ACL injured and uninjured pediatric athletes. A total of 140 high-school aged athletes comprising 70 athletes who went on to sustain an ACL injury between 2012 and 2018 and 70 age- and sex-matched uninjured controls were included in the study. Mean reaction times were similar for the injured (0.67 s) and uninjured (0.66 s) athletes (p = 0.432), and the impulse control scores were also similar for those with (5.67) and without (6.07) an ACL injury (p = 0.611). Therefore, neurocognitive risk factors for sustaining an ACL injury in adults cannot necessarily be extrapolated to adolescent athletes. Further research is needed to understand why differences exist between injury risk in youth and adult athletes.

Emotion understanding (EU) ability is associated with healthy social functioning and psychological well-being. Across three studies, we develop and present validity evidence for the Core Relational Themes of Emotions (CORE) Test. The test measures people’s ability to identify relational themes underlying 19 positive and negative emotions. Relational themes are consistencies in the meaning people assign to emotional experiences. In Study 1, we developed and refined the test items employing a literature review, expert panel, and confusion matrix with a demographically diverse sample. Correctness criteria were determined using theory and prior research, and a progressive (degrees of correctness) paradigm was utilized to score the test. In Study 2, the CORE demonstrated high internal consistency and a confirmatory factor analysis supported the unidimensional factor structure. The CORE showed evidence of convergence with established EU ability measures and divergent relationships with verbal intelligence and demographic characteristics, supporting its construct validity. Also, the CORE was associated with less relational conflict. In Study 3, the CORE was associated with more adaptive and less maladaptive coping and higher well-being on multiple indicators. A set of effects remained, accounting for variance from a widely used EU test, supporting the CORE’s incremental validity. Theoretical and methodological contributions are discussed.

A quantum register coupled to a spin-photon interface is a key component in quantum communication and information processing. Group-IV color centers in diamond (SiV^{−}, GeV^{−}, and SnV^{−}) are promising candidates for this application, comprising an electronic spin with optical transitions coupled to a nuclear spin as the quantum register. However, the creation of a quantum register for these color centers with deterministic and strong coupling to the spin-photon interface remains challenging. Here, we make first-principles predictions of the hyperfine parameters of the group-IV color centers, which we verify experimentally with a comprehensive comparison between the spectra of spin active and spin neutral intrinsic dopant nuclei in single GeV^{−} and SnV^{−} emitters. In line with the theoretical predictions, detailed spectroscopy on large sample sizes reveals that hyperfine coupling causes a splitting of the optical transition of SnV^{−} an order of magnitude larger than the optical line width and provides a magnetic field insensitive transition. This strong coupling provides access to a new regime for quantum registers in diamond color centers, opening avenues for novel spin-photon entanglement and quantum sensing schemes for these well-studied emitters.

Introduction: Childhood overweight and obesity are major public health problems globally, including in Ecuador, and there is increasing interest in intervening as early as possible. We previously developed and evaluated a behavioural and educational intervention aiming to improve diet and physical activity habits among children at municipal preschools in Cuenca, Ecuador, after which it was implemented. Objective: To describe some of the key lessons learned in the process of intervention development, evaluation, and implementation. Methods: We conducted program evaluation using a survey questionnaire with open-ended questions with the coordinators, teachers, and kitchen staff of the preschools that participated in the intervention. Results: Human resource changes were a threat to the continued success of the intervention; therefore, these changes need to be anticipated and peer training emphasized. Careful consideration also needs to be given to impact on preschool staff workload. Teachers and other stakeholders like administrators should take ownership of the intervention and play a leadership role, distinct from that of researchers. Regarding the intervention itself, we identified that both fidelity and adaptability were critical for continued success. Conclusion: Lessons learned from our setting may be useful to inform the design, evaluation, and implementation of sustainable preschool-based interventions aiming to improve diet and physical activity habits elsewhere.

Abstract Objective To comprehensively review the recent published literature to characterize current trends of burnout and well‐being among otolaryngology trainees. Methods Study design: systematic review and meta‐analysis. A comprehensive literature review from 2000 to 2021 of studies related to otolaryngology resident burnout and well‐being, as well as the general topic of well‐being among surgical residents was completed. All included studies were summarized qualitatively. For the quantitative analysis, only articles reporting a Maslach burnout inventory (MBI), modified MBI or Mini‐Z‐ Burnout assessment were included. Results Twenty‐five articles were included in the qualitative summary and nine articles in the quantitative analysis. In the qualitative summary, trainees were reported to have increased levels of distress and emotional hardening compared to attending otolaryngologists. Total hours worked per week and female gender were associated with worsened well‐being. Residency program strategies to improve trainee well‐being include program‐sponsored wellness activities, dedicated wellness champions, and assistance with clerical burden. Implementation of protected nonclinical time has been shown to decrease burnout and increase well‐being among trainees. Moreover, formal trainee mentorship programs have also been shown to reduce trainee burnout and stress. In the quantitative analysis, rates of trainee burnout ranged from 29.7% to 86% with an overall trend towards reduced rates of burnout from 2006 to 2021. Utilizing a weighted average, the overall burnout among otolaryngology residents was 58.6%. Conclusions Rates of burnout remain high among otolaryngology trainees. Implementing formal mentorship programs and providing protected time during regular work hours appear to be effective tools to improve resident well‐being.

Abstract Technical noise present in laser systems can limit their ability to perform high fidelity quantum control of atomic qubits. The ultimate fidelity floor for atomic qubits driven with laser radiation is due to spontaneous emission from excited energy levels. The goal is to suppress the technical noise from the laser source to below the spontaneous emission floor such that it is no longer a limiting factor. It has been shown that the spectral structure of control noise can have a large influence on achievable control fidelities, while prior studies of laser noise contributions have been restricted to noise magnitudes. Here, we study the unique spectral structure of laser noise and introduce a metric that determines when a stabilised laser source has been optimised for quantum control of atomic qubits. We find requirements on stabilisation bandwidths that can be orders of magnitude higher than those required to simply narrow the linewidth of a laser. The introduced metric, the χ-separation line, provides a tool for the study and engineering of laser sources for quantum control of atomic qubits below the spontaneous emission floor.

Our objective is to define a standard protocol for post-partum salpingectomy and provide a prospective assessment of safety and feasibility of such a procedure. Thus, a protocol for performing post-partum salpingectomy in limited-resource environments was created based on contemporary practices for tubal ligation. Gravidae presenting for post-partum tubal ligation following vaginal delivery or at time of cesarean were prospectively approached and, if consent was obtained, enrolled. Outcomes were compared to a historical cohort of gravidae who underwent standard post-partum tubal ligation following vaginal birth or at the time of cesarean as per institutional standard of care. The primary outcome was operative time. One hundred and fifty-seven subjects underwent post-partum salpingectomy following cesarean or vaginal delivery (on post-partum days 0–2). Post-partum salpingectomy performed after vaginal delivery (n = 97) resulted in slightly longer operative times (39.1 ± 11.8 vs. 34.3 ± 13.1 min, p = 0.003) and slightly greater blood loss (21.0 ± 22.0 vs. 13.4 ± 17.3 mL, p = 0.001) than modified Pomeroy tubal ligation (n = 200). Post-partum salpingectomy at cesarean resulted in no difference in estimated blood loss, but slightly longer operative times compared to Parkland tubal ligations (99.5 ± 47.3 vs. 86.5 ± 33.9 min, p = 0.048). Surgical complications for post-partum salpingectomy were similar to controls, regardless of when the procedure was performed. In conclusion, a standardized protocol created for post-partum salpingectomy using suture ligation is feasible and safe.

Aims: To compare the cost-utility of removable brace compared with cast in the management of adult patients with ankle fracture. Methods: A within-trial economic evaluation conducted from the UK NHS and personnel social services (PSS) perspective. Health resources and quality-of-life data were collected as part of the Ankle Injury Rehabilitation (AIR) multicentre, randomized controlled trial over a 12-month period using trial case report forms and patient-completed questionnaires. Cost-utility analysis was estimated in terms of the incremental cost per quality adjusted life year (QALY) gained. Estimate uncertainty was explored by bootstrapping, visualized on the incremental cost-effectiveness ratio plane. Net monetary benefit and probability of cost-effectiveness were evaluated at a range of willingness-to-pay thresholds and visualized graphically. Results: The incremental cost and QALYs of using brace over a 12-month period were £46.73 (95% confidence interval (CI) £-9 to £147) and 0.0141 (95% CI -0.005 to 0.033), respectively. The cost per QALY gained was £3,318. The probability of brace being cost-effective at a £30,000 per QALY willingness-to-pay threshold was 88%. The results remained robust to a range of sensitivity analyses. Conclusion: This within-trial economic evaluation found that it is probable that using a removable brace provides good value to the NHS when compared to cast, in the management of adults with ankle fracture. Cite this article: Bone Jt Open 2022;3(6):455–462.

Chimeric antigen receptor T cells represent a breakthrough treatment in hematologic malignancies, but insufficient level of cytotoxicity and persistence of T cells might compromise success. Authors show here that a recombinant long acting form of interleukin-7 enhances proliferation, persistence and cytotoxicity of the engineered T cells, resulting in long term disease remission.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Aims: This study aims to estimate economic outcomes associated with 30-day deep surgical site infection (SSI) from closed surgical wounds in patients with lower limb fractures following major trauma. Methods: Data from the Wound Healing in Surgery for Trauma (WHiST) trial, which collected outcomes from 1,547 adult participants using self-completed questionnaires over a six-month period following major trauma, was used as the basis of this empirical investigation. Associations between deep SSI and NHS and personal social services (PSS) costs (£, 2017 to 2018 prices), and between deep SSI and quality-adjusted life years (QALYs), were estimated using descriptive and multivariable analyses. Sensitivity analyses assessed the impact of uncertainty surrounding components of the economic analyses. Results: Compared to participants without deep SSI, those with deep SSI had higher mean adjusted total NHS and PSS costs (adjusted mean difference £1,577 (95% confidence interval (CI) -951 to 4,105); p = 0.222), and lower mean adjusted QALYs (adjusted mean difference -0.015 (95% CI -0.032 to 0.002); p = 0.092) over six months post-injury, but this difference was not statistically significant. The results were robust to the sensitivity analyses performed. Conclusion: This study found worse economic outcomes during the first six months post-injury in participants who experience deep SSI following orthopaedic surgery for major trauma to the lower limb. However, the increase in cost associated with deep SSI was less than previously reported in the orthopaedic trauma literature. Cite this article: Bone Jt Open 2022;3(5):398–403.

Purpose: Infection after distal radius fracture fixation can be a devastating complication, leading to potential hardware removal, prolonged antibiotic courses, multiple office visits, and increased costs. This study aimed to identify potential risk factors for infectious complications after distal radius fracture fixation and assess the impacts on cost. Methods: This study used the PearlDiver national database, encompassing 53 million unique patients from January 1, 2010, to March 31, 2020. The cohort included patients undergoing distal radius fracture fixation. The endpoint was postoperative infection within 180 days of fixation. Two-sample t test was used to compare rates of infection between open and percutaneous fracture fixation techniques. A propensity-matched cohort was created using patient age, gender, and open fracture. Logistic regression analyses defined independent risk factors for developing a postoperative infection among all patients and within the matched cohorts. A Mann-Whitney U test was used to compare costs of care with and without infection. Results: The database included 87,169 patients who underwent distal radius fracture fixation. Postoperative infections were identified in 781 patients (0.9%). There was a significant difference in rates of postoperative infection with percutaneous fixation (1.3%) versus open fixation (0.8%). Logistic regression analysis identified male gender, open fracture, lung disease, chronic kidney disease, diabetes, hypertension, liver disease, obesity, and tobacco to be independent risk factors for developing a postoperative infection. Logistic regression analysis of the propensity-matched cohorts identified tobacco use as a significant risk factor. The average cost of care for patients undergoing fracture fixation without an infection was $6,383, versus $23,355 for those with an infection, which was significantly different. Conclusions: Multiple risk factors for postoperative infection were identified. Cost is significantly increased after postoperative infection, by almost 4-fold. Attempts to correct or optimize modifiable risk factors may lead to substantial cost savings, and potentially decreased rates of infection. Type of study/level of evidence: Prognostic III.

The role of MYC in transcriptional reprogramming in prostate cancer remains poorly characterized. Here, MYC overexpression antagonizes the canonical AR transcriptional program leading to prostate tumor initiation and progression by disrupting transcriptional pause release at AR-regulated genes.

The recent integration of citizen science with modern technology has greatly increased its applications and has allowed more people than ever to contribute to research across all areas of science. In particular, citizen science has been instrumental in the detection and monitoring of novel introduced species across the globe. This study provides the first records of Miomantis caffra Saussure, 1871, the South African Mantis, from the Australian mainland and uses records from four different citizen science and social media platforms in conjunction with museum records to track the spread of the species through the country. A total of 153 wild mantises and oothecae were observed across four states and territories (New South Wales, Norfolk Island, Victoria, and Western Australia) between 2009 and 2021. The large number of observations of the species in Victoria and the more recent isolated observations in other states and territories suggest that the species initially arrived in Geelong via oothecae attached to plants or equipment, likely from the invasive population in New Zealand. From there it established and spread outwards to Melbourne and eventually to other states and territories, both naturally and with the aid of human transport. We also provide a comparison of M. caffra to similar native mantises, specifically Pseudomantis albofimbriata (Stål, 1860), and comment on the potential impact and further spread of the species within Australia. Finally, we reiterate the many benefits of engaging directly with citizen scientists in biodiversity research and comment on the decision to include them in all levels of this research investigation.

The Shelta Cave Crayfish (Orconectes sheltae) is a small, cave-obligate member of the genus Orconectes (family Cambaridae) endemic to a single cave system—Shelta Cave—in northwest Huntsville, Madison Co., Alabama, USA. Although never abundant, this stygobiont was regularly observed in the 1960s and early 1970s before the population and aquatic community in general at Shelta Cave collapsed likely in response to groundwater contamination and the loss of energetic inputs from a Grey Bat (Myotis grisescens) maternity colony that abandoned the cave after installation of a poorly designed cave gate. We conducted 20 visual surveys of aquatic habitats at Shelta Cave between October 2018 and July 2021. Although the aquatic community has not recovered, we did confirm the continued existence of O. sheltae, which had not been observed in 31 years, with observations of an adult female on 31 May 2019 and an adult male on 28 August 2020. We conducted the first phylogenetic analyses of O. sheltae and discovered that the species is most closely related to other geographically proximate stygobiotic crayfishes in the genus Cambarus in northern Alabama than members of the genus Orconectes. We advocate for recognition of this species as Cambarus sheltae to more accurately reflect evolutionary relationships of this single-cave endemic and offer recommendations for its management, conservation, and future research, as this species remains at high risk of extinction.

Abstract Background The first and most recent nationwide audit of palliative care services in Uganda was conducted in 2009. Since then, Uganda has made great strides in palliative care development, including policy, education, and services implementation. This study provides an overview of the availability of palliative care services in the country and the challenges and gaps in Uganda prior to the global COVID-19 pandemic. This lays the foundation for better understanding the challenges and changes needed to support palliative care development and access in the wake of the pandemic. Methods We conducted a descriptive quantitative study of secondary data on nationwide morphine distribution, collated a list of accredited facilities, and analyzed key palliative care indicators collected through the mHealth surveillance project present at a subset of accredited facilities. Descriptive statistical analysis involved non-parametric tests using SPSS, mapping geographical distribution of available palliative care services using Geographic Information Systems software, and identification of challenges from the subset of accredited facilities. Results There were 226 accredited palliative care facilities across Uganda’s 135 districts in 2020. Thirty districts lacked any accredited palliative care facility. The estimated population coverage was 88.5%. The majority (68.1%) of accredited facilities were public, and private facilities received slightly more pain-relieving morphine. There was an alternating trend in the volumes of morphine delivered to public and private facilities. More than a third of the patients were diagnosed with non-communicable diseases, highlighting their significance alongside cancer and HIV/AIDS as conditions requiring palliative care. Palliative care accredited facilities offered six types of services: outreach, home visits, psychosocial, legal, bereavement, and spiritual support, but only for an average of 7 months a year due to lack of facilitation and transportation. Conclusion Palliative care in Uganda developed in quality, volume, and geographic coverage since 2009. The shift in palliative care patients’ primary diagnosis from HIV/AIDS to non-communicable diseases marks an important epidemiologic transition. Although accredited facilities are present in most administrative districts, more research is needed to evaluate the actual accessibility of these services. The existing services, both private and public, are limited by the amount of pain-relieving morphine, financial and transport resources. More quality data collected on key palliative care indicators is needed into geographical accessibility of palliative care services, morphine availability trends, and patient diagnoses in order to improve the provision of palliative care in Uganda.

Aims The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells. Methods HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%. Conclusion The HIPGEN study assesses the efficacy, safety, and tolerability of intramuscular PLX-PAD administration for the treatment of muscle injury following arthroplasty for hip fracture. It is the first phase III study to investigate the effect of an allogeneic cell therapy on improved mobilization after hip fracture, an aspect which is in sore need of addressing for the improvement in standard of care treatment for patients with FNF. Cite this article: Bone Jt Open 2022;3(4):340–347.

Following androgen receptor pathway inhibition prostate cancers can differentiate towards the neuroendocrine lineage. Here, the authors identify epigenetic alterations regulated by ASCL1 and suggest targeting ASCL1 to reverse the neuroendocrine phenotype.

Abstract Tidal marsh survival in the face of sea level rise (SLR) and declining sediment supply often depends on the ability of marshes to build soil vertically. However, numerical models typically predict survival under rates of SLR that far exceed field‐based measurements of vertical accretion. Here, we combine novel measurements from seven U.S. Atlantic Coast marshes and data from 70 additional marshes from around the world to illustrate that—over continental scales—70% of variability in marsh accretion rates can be explained by suspended sediment concentratin (SSC) and spring tidal range (TR). Apparent discrepancies between models and measurements can be explained by differing responses in high marshes and low marshes, the latter of which accretes faster for a given SSC and TR. Together these results help bridge the gap between models and measurements, and reinforce the paradigm that sediment supply is the key determinant of wetland vulnerability at continental scales.

Ceftibuten, C15H14N4O6S2, with the systematic name (6R,7R)-7-{[(Z)-2-(2-amino-1,3-thiazol-4-yl)-4-carboxybut-2-enoyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, is a third generation, orally administered cephalosporin antibiotic with broad antimicrobial activity and stability against extended spectrum β-lactamases. Ceftibuten can exist in various hydration states and to better understand the location of the water molecules of crystallization and their effect on the structure, the crystal structures of anhydrous (I) and hydrated (II) ceftibuten were determined and both occur as zwitterions with proton transfer from the carboxylate group adjacent to the β-lactam ring to the N atom of the thiazole ring. The β-lactam ring in (I) is almost planar but the equivalent grouping in (II) is slightly buckled. In the extended structure of (I), O—H...O and N—H...O hydrogen bonds link the molecules into a three-dimensional network. In (II), O—H...Oc, N—H...Oc, O—H...Ow, N—H...Ow and Ow—H...Ow (c = ceftibuten, w = water) hydrogen bonds link the components into a three-dimensional network. A large void space is present within the anhydrous crystal structure that can accommodate between two and three molecules of water.

The beetle fauna of the California Channel Islands is here enumerated for the first time in over 120 years. We provide an annotated checklist documenting species-by-island diversity from an exhaustive literature review and analysis of a compiled dataset of 26,609 digitized specimen records to which were added over 3,000 individual specimen determinations. We report 825 unique species from 514 genera and 71 families (including 17 new family records) comprising 1,829 species-by-island records. Species totals for each island are as follows: Anacapa (74); San Clemente (197); San Miguel (138); San Nicolas (146); Santa Barbara (64); Santa Catalina (370); Santa Cruz (503); and Santa Rosa (337). This represents the largest list of species published to date for any taxonomic group of animals on the Channel Islands; despite this, we consider the checklist to be preliminary. We present evidence that both inventory and taxonomic efforts on Channel Islands beetles are far from complete. Rarefaction estimates indicate there are at least several hundred more species of beetles yet to be recorded from the islands. Despite the incomplete nature of existing records, we found that species diversity is highly correlated with island area. We report 56 species which are putatively geographically restricted (endemic) to the Channel Islands, with two additional species of questionable endemic status. We also report 52 species from the islands which do not natively occur in the southern California region.

Manta rays (Mobula alfredi and M. birostris) are poorly understood in South Africa, despite their ecological importance and charismatic appeal. This study analyzed a 41-year dataset from the KwaZulu-Natal bather protection program to investigate catch per unit effort between 1981-2021. We used Generalized Additive Models and the probability of encounter to assess annual and seasonal trends, as well as the effect of location and moon phases on catch rates. We also evaluated the size composition and demographics of caught manta rays using the same dataset. Our analysis revealed a significant decline in overall manta ray catches since the late 1990s (p

In pulmonary arterial hypertension (PAH), inflammation promotes a fibroproliferative pulmonary vasculopathy. Reductionist studies emphasizing single biochemical reactions suggest a shift toward glycolytic metabolism in PAH; however, key questions remain regarding the metabolic profile of specific cell types within PAH vascular lesions in vivo. We used RNA-Seq to profile the transcriptome of pulmonary artery endothelial cells (PAECs) freshly isolated from an inflammatory vascular injury model of PAH ex vivo, and these data were integrated with information from human gene ontology pathways. Network medicine was then used to map all aa and glucose pathways to the consolidated human interactome, which includes data on 233,957 physical protein-protein interactions. Glucose and proline pathways were significantly close to the human PAH disease module, suggesting that these pathways are functionally relevant to PAH pathobiology. To test this observation in vivo, we used multi-isotope imaging mass spectrometry to map and quantify utilization of glucose and proline in the PAH pulmonary vasculature at subcellular resolution. Our findings suggest that elevated glucose and proline avidity underlie increased biomass in PAECs and the media of fibrosed PAH pulmonary arterioles. Overall, these data show that anabolic utilization of glucose and proline are fundamental to the vascular pathology of PAH.

ABSTRACT Transposable elements (TEs) are mobile genomic sequences that encompass roughly 50% of the human genome. Class 1 TEs, or “retrotransposons,” mobilize through the production of an RNA intermediate that is then reverse transcribed to form complementary DNA (cDNA) molecules capable of genomic reinsertion. While TEs are traditionally silenced to maintain genomic integrity, the recognition of immunostimulatory cues, such as those provided by microorganisms, drastically alters host transcription to induce the differential expression of TEs. Emerging evidence demonstrates that the inducible production of TE cDNA is not an inert phenomenon but instead has been coopted by host immunity to facilitate cross talk between host and constituents of the microbiota by agonizing intrinsic antiviral receptors. Here, we demonstrate that immunostimulation of toll-like receptor 4 (TLR4) with lipopolysaccharide (LPS) and TLR5 with bacterial flagella (FLA) alters the expression of retrotransposons, such as human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs). Next, we demonstrate that reverse transcriptase inhibitor (RTi) delivery ameliorates the acute production of the proinflammatory cytokine “tumor necrosis factor alpha” (TNF-α) in response to FLA in a monocytic cell line (THP-1). Collectively, our findings demonstrate that TLR5-mediated cross talk between the host and microbiota is partially dependent on the reverse transcription (RT) of retrotransposons. IMPORTANCE The microbiota is a potent reservoir of immunostimulatory and immunosuppressive motifs that fundamentally shape host immunity. Despite broad associations between microbial composition and host immunity, the mechanisms underlying host microbiota-induced immunoregulation remain poorly defined. Here, we demonstrate a novel mechanism by which motifs overabundant during dysbiotic conditions influence host immunity through the upregulation of endogenous RT to produce motifs that agonize antiviral receptors.

Abstract Objective Otolaryngology residency is highly competitive, and applicant academic metrics are scrutinized. The predictive value of preresidency academic metrics on applicants’ future research productivity and career aspirations remains largely undefined. Study Design Retrospective cohort study Setting Academic otolaryngology department, 2014 to 2015. Methods Applicant demographics, publication history, and United States Medical Licensing Examination (USMLE) scores were downloaded from Electronic Residency Application Service archives. Publications during residency were tallied from all PubMed articles indexed between July 1, 2015 and June 30, 2020. Postresidency career paths were examined by 2 investigators (D.J.C. and L.X.Y.) using Google searches with an emphasis on program websites, Doximity, and LinkedIn profiles. Associations with publication potential and postresidency positions were evaluated with Spearman rank correlation coefficients and Kruskal‐Wallis, Wilcoxon rank sum, and χ2 tests. Results Of 321 applicants, 226 (70%) matched, and 205 (64%) completed residency by June 2020. Matched residents published a median of 4 (range: 0‐41) manuscripts during residency. USMLE scores, Alpha Omega Alpha status, and the number of preresidency publications did not significantly correlate with publication potential during residency. The number of research experiences had a significant positive correlation with publications during residency (p

Many marine fish species are experiencing population declines, but their extinction risk profiles are largely understudied in comparison to their terrestrial vertebrate counterparts. Selective extinction of marine fish species may result in rapid alteration of the structure and function of ocean ecosystems. In this study, we compiled an ecological trait dataset for 8,185 species of marine ray-finned fishes (class Actinopterygii) from FishBase and used phylogenetic generalized linear models to examine which ecological traits are associated with increased extinction risk, based on the International Union for the Conservation of Nature Red List. We also assessed which threat types may be driving these species toward greater extinction risk and whether threatened species face a greater average number of threat types than non-threatened species. We found that larger body size and/or fishes with life histories involving movement between marine, brackish, and freshwater environments are associated with elevated extinction risk. Commercial harvesting threatens the greatest number of species, followed by pollution, development, and then climate change. We also found that threatened species, on average, face a significantly greater number of threat types than non-threatened species. These results can be used by resource managers to help address the heightened extinction risk patterns we found.

Brain imaging research studies increasingly use “de-facing” software to remove or replace facial imagery before public data sharing. Several works have studied the effects of de-facing software on brain imaging biomarkers by directly comparing automated measurements from unmodified vs de-faced images, but most research brain images are used in analyses of correlations with cognitive measurements or clinical statuses, and the effects of de-facing on these types of imaging-to-cognition correlations has not been measured. In this work, we focused on brain imaging measures of amyloid (A), tau (T), neurodegeneration (N), and vascular (V) measures used in Alzheimer’s Disease (AD) research. We created a retrospective sample of participants from three age- and sex-matched clinical groups (cognitively unimpaired, mild cognitive impairment, and AD dementia, and we performed region- and voxel-wise analyses of: hippocampal volume (N), white matter hyperintensity volume (V), amyloid PET (A), and tau PET (T) measures, each from multiple software pipelines, on their ability to separate cognitively defined groups and their degrees of correlation with age and Clinical Dementia Rating (CDR)–Sum of Boxes (CDR-SB). We performed each of these analyses twice: once with unmodified images and once with images de-faced with leading de-facing software mri_reface, and we directly compared the findings and their statistical strengths between the original vs. the de-faced images. Analyses with original and with de-faced images had very high agreement. There were no significant differences between any voxel-wise comparisons. Among region-wise comparisons, only three out of 55 correlations were significantly different between original and de-faced images, and these were not significant after correction for multiple comparisons. Overall, the statistical power of the imaging data for AD biomarkers was almost identical between unmodified and de-faced images, and their analyses results were extremely consistent.

Purpose: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and demyelination. This study aims to clarify (1) the pattern of susceptibility in PAOS patients, (2) the susceptibility differences between the phonetic (characterized by predominance of distorted sound substitutions and additions) and prosodic (characterized by predominance of slow speech rate and segmentation) subtypes of PAOS, and (3) the relationships between susceptibility and symptom severity. Methods: Twenty patients with PAOS (nine phonetic and eleven prosodic subtypes) were prospectively recruited and underwent a 3 Tesla MRI scan. They also underwent detailed speech, language, and neurological evaluations. Quantitative susceptibility maps (QSM) were reconstructed from multi-echo gradient echo MRI images. Region of interest analysis was conducted to estimate susceptibility coefficients in several subcortical and frontal regions. We compared susceptibility values between PAOS and an age-matched control group and performed a correlation analysis between susceptibilities and an apraxia of speech rating scale (ASRS) phonetic and prosodic feature ratings. Results: The magnetic susceptibility of PAOS was statistically greater than that of controls in subcortical regions (left putamen, left red nucleus, and right dentate nucleus) (p

Hippocampal subfields (HCsf) are brain regions important for memory function that are vulnerable to decline with amnestic mild cognitive impairment (aMCI), which is often a preclinical stage of Alzheimer’s disease. Studies in aMCI patients often assess HCsf tissue integrity using measures of volume, which has little specificity to microstructure and pathology. We use magnetic resonance elastography (MRE) to examine the viscoelastic mechanical properties of HCsf tissue, which is related to structural integrity, and sensitively detect differences in older adults with aMCI compared to an age-matched control group. Group comparisons revealed HCsf viscoelasticity is differentially affected in aMCI, with CA1-CA2 and DG-CA3 exhibiting lower stiffness and CA1-CA2 exhibiting higher damping ratio, both indicating poorer tissue integrity in aMCI. Including HCsf stiffness in a logistic regression improves classification of aMCI beyond measures of volume alone. Additionally, lower DG-CA3 stiffness predicted aMCI status regardless of DG-CA3 volume. These findings showcase the benefit of using MRE in detecting subtle pathological tissue changes in individuals with aMCI via the HCsf particularly affected in the disease.

Background:. Breast cancer impacts millions of people yearly affecting various aspects of their lives—including but not limited to mental health. Patients with a known psychiatric history, specifically generalized anxiety disorder (GAD) and/or depression, have previously been shown to have an increased number of revisions after breast reconstruction. Methods:. A commercially available database of 91 million unique patients, PearlDiver, was used to identify patients with breast cancer who underwent autologous free flap breast reconstruction. An average number of revisions were calculated from each group of patients—those with a history of anxiety and/or depression and patients without a history of anxiety and/or depression. A logistic regression was performed to determine risk factors associated with patients undergoing revision surgery. Results:. A total of 39,683 patients with a history of breast cancer underwent autologous breast reconstruction between 2010 and 2020, of which 6308 (15.9%) patients had a history of GAD and/or depression before autologous reconstruction. A total of 13,422 (33.8%) patients received at least one revision surgery. Patients with GAD only, depression only, and concomitant GAD and depression received 1.40 revisions each with no significant differences between the control and any of the study groups (P = 0.956). Logistic regression did not find psychiatric history to be associated with patients undergoing revision surgery (OR, 0.94; 95% CI, 0.89–1.00). Conclusion:. Patients who underwent autologous reconstruction for breast cancer demonstrated no difference in rates of secondary surgical revision, regardless of a concurrent mental health history.

Due to immunosuppressive cancer therapies, cancer patients diagnosed with COVID-19 have a higher chance of developing severe symptoms and present a higher mortality rate in comparison to the general population. Here we show a comparative analysis of the microbiome from naso-oropharyngeal samples of breast cancer patients with respect to SARS-CoV-2 status and identified bacteria associated with symptom severity. Total DNA of naso-oropharyngeal swabs from 74 women with or without breast cancer, positive or negative for SARS-CoV-2 were PCR-amplified for 16S-rDNA V3 and V4 regions and submitted to massive parallel sequencing. Sequencing data were analyzed with QIIME2 and taxonomic identification was performed using the q2-feature-classifier QIIME2 plugin, the Greengenes Database, and amplicon sequence variants (ASV) analysis. A total of 486 different bacteria were identified. No difference was found in taxa diversity between sample groups. Cluster analysis did not group the samples concerning SARS-CoV-2 status, breast cancer diagnosis, or symptom severity. Three taxa (Pseudomonas, Moraxella, and Klebsiella,) showed to be overrepresented in women with breast cancer and positive for SARS-CoV-2 when compared to the other women groups, and five bacterial groups were associated with COVID-19 severity among breast cancer patients: Staphylococcus, Staphylococcus epidermidis, Scardovia, Parasegitibacter luogiensis, and Thermomonas. The presence of Staphylococcus in COVID-19 breast cancer patients may possibly be a consequence of nosocomial infection.

BackgroundIn sub-Saharan Africa, truckers and female sex workers (FSWs) have high HIV risk and face challenges accessing HIV testing. Adding HIV self-testing (HIVST) to standard of care (SOC) programs increases testing rates. However, the underlying mechanisms are not fully understood. HIVST may decrease barriers (inconvenient clinic hours, confidentiality concerns) and thus we would expect a greater impact among those not accessing SOC testing (barriers prevented previous testing). As a new biomedical technology, HIVST may also be a cue to action (the novelty of a new product motivates people to try it), in which case we might expect the impact to be similar by testing history.MethodsWe used data from two randomized controlled trials evaluating the announcement of HIVST availability via text-message to male truckers (n = 2,260) and FSWs (n = 2,196) in Kenya. Log binomial regression was used to estimate the risk ratio (RR) for testing ≤ 2 months post-announcement in the intervention vs. SOC overall and by having tested in the previous 12-months (12m-tested); and we assessed interaction between the intervention and 12m-tested. We also estimated risk differences (RD) per 100 and tested additive interaction using linear binomial regression.ResultsWe found no evidence that 12m-tested modified the HIVST impact. Among truckers, those in the intervention were 3.1 times more likely to test than the SOC (p < 0.001). Although testing was slightly higher among those not 12m-tested (RR = 3.5, p = 0.001 vs. RR = 2.7, p = 0.020), the interaction was not significant (p = 0.683). Among FSWs, results were similar (unstratified RR = 2.6, p < 0.001; 12m-tested: RR = 2.7, p < 0.001; not 12m-tested: RR = 2.5, p < 0.001; interaction p = 0.795). We also did not find significant interaction on the additive scale (truckers: unstratified RD = 2.8, p < 0.001; 12m-tested RD = 3.8, p = 0.037; not 12m-tested RD = 2.5, p = 0.003; interaction p = 0.496. FSWs: unstratified RD = 9.7, p < 0.001; 12m-tested RD = 10.7, p < 0.001, not 12m-tested RD = 9.1, p < 0.001; interaction p = 0.615).ConclusionThe impact of HIVST was not significantly modified by 12m-tested among truckers and FSWs on the multiplicative or additive scales. Announcing the availability of HIVST likely served primarily as a cue to action and testing clinics might maximize the HIVST benefits by holding periodic HIVST events to maintain the cue to action impact rather than making HIVST continually available.