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Binders used in binder jetting often pose health and environmental risks during processing and post processing operations. The print-heads which are used to deposit binder selectively on the feedstock are prone to clogging, despite the trend of print-heads being highly customised to suit different kinds of binders. These factors often hide the advantages of binder jetting as an additive manufacturing process, especially its scalability and its faster printing rates in comparison to powder bed fusion methods. The work presented here takes a step back and focuses on the development of an aqueous, polyvinyl alcohol (PVA)-based liquid binder that is easy to manufacture and store, safe to handle, and can be reliably jetted to print parts. The feedstock considered was Inconel 718, a nickel-based super alloy which can be effectively processed by binder jetting without niobium segregation. PVA was added to the Inconel 718 powder in dry, granular form to manufacture a modified feedstock. The study also investigated the role of molecular weight of the PVA used, sintering environments and post-processing methods like hot isostatic pressing (HIP) on process responses like part densification, tensile strength, and hardness. Three different types of PVA were chosen which had molecular weights 10,000 g/mol (low molecular weight or LMW), 26,000 g/mol (medium molecular weight or MMW), and 84,000 g/mol (high molecular weight or HMW). The compatibility of the liquid, aqueous PVA-based binders with virgin Inconel 718 was examined by measuring the contact angle. The liquid, aqueous binder having MMW PVA reported better wetting with the Inconel 718 powder with a wetting angle of 26.6 which was lower than the wetting angle of 42.4°, seen in case of a commercial resin-based binder. The green strength reported by the MMW PVA liquid binder was 220 kPa which was higher than the other two PVA-based liquid binders. Green parts, upon successful printing, were sintered at 1260 °C. It was observed that a part printed using MMW PVA had a densification of 96.16% when sintered in 99.98% by volume argon gas, which increased to 98.96% after undergoing HIP. The same part reported a densification of 88.69% when sintered in a 95% by volume N2 and 5% by volume H2 gaseous environment, which was later attributed to the uptake of nitrogen by the chromium present in Inconel 718, which prevented necking between particles. Tensile specimens printed using MMW PVA, sintered in a 99.98% argon environment, showed the highest ultimate tensile strength of 220 MPa, which increased to 1010 MPa after the HIP process, which can be compared to commercially available Inconel 718. [ABSTRACT FROM AUTHOR]

Mantis shrimp (Stomatopoda) are extant, marine, predatory arthropods, but these malacostracan pancrustaceans are also occasionally preserved in fossil assemblages, particularly in Carboniferous and Cretaceous deposits. Carboniferous species fall into two suborders—Palaeostomatopodea and Archaeostomatopodea—and represent the ancestral forms that gave rise to modern lineages. Herein, we describe hitherto unknown specimens belonging to the archaeostomatopod genus Tyrannophontes from the Pennsylvanian-aged Wea Shale Member, eastern Nebraska. We explore the preservation of these fossils using scanning electron microscopy and energy dispersive X-ray spectroscopy. These approaches reveal additional morphological characteristics, including unique appendicular data, such as the earliest occurrence of biramous gilled appendages in Stomatopoda. We suggest that further examination of black shales will likely uncover novel records of these rare pancrustaceans. [ABSTRACT FROM AUTHOR]

The following case report demonstrates a case of a chronic irreducible patellar dislocation, age‐indeterminate associated with a large medial patellar avulsion fracture that was treated with a vastus medialis obliquus advancement following an extensive lateral release. This case is the only known report of this kind in the literature. The patient is a 41‐year‐old Caucasian female who presented to the clinic with an age‐indeterminate, chronically dislocated patella. She has a past medical history of hypertension and ischemic stroke 1 year prior to presentation, leading to expressive aphasia and lower extremity weakness in addition to patellar instability dating back to age 13. An unsuccessful patellofemoral reduction was performed at an outside clinic, and she was placed in a knee immobilizer and referred to our office. Clinically, the patient had limited knee range of motion with a fixed lateral patellar dislocation that was confirmed on imaging. This case report demonstrates a surgical reduction technique that can be utilized by orthopedic surgeons for chronic patellar dislocations that are not amenable to routine patellar instability surgeries due to the contraction of surrounding soft tissue, chronic bone abnormalities, and position of the chronic dislocation. An extensive lateral release followed by vastus medialis obliquus advancement was performed to center the patella within the trochlear groove and to allow for stable articulation throughout range of motion. The patient was able to regain painless, full range of motion of her knee postoperatively with patellar stability noted on both physical exam and radiographic imaging. [ABSTRACT FROM AUTHOR]

Recent calls to address racism in bioethics reflect a sense of urgency to mitigate the lethal effects of a lack of action. While the field was catalyzed largely in response to pivotal events deeply rooted in racism and other structures of oppression embedded in research and health care, it has failed to center racial justice in its scholarship, pedagogy, advocacy, and practice, and neglected to integrate anti-racism as a central consideration. Academic bioethics programs play a key role in determining the field's norms and practices, including methodologies, funding priorities, and professional networks that bear on equity, inclusion, and epistemic justice. This article describes recommendations from the Racial Equity, Diversity, and Inclusion (REDI) Task Force commissioned by the Association of Bioethics Program Directors to prioritize and strengthen anti-racist practices in bioethics programmatic endeavors and to evaluate and develop specific goals to advance REDI. [ABSTRACT FROM AUTHOR]

Trilobites with malformations present important insight into the paleoecology of the wholly extinct arthropod group. This includes records of failed predation, developmental complications, and parasitic interactions. The documentation of malformed trilobites therefore allows for a more thorough understanding of these animals. Such summaries also permit larger-scale, synthetic works that consider patterns and processes associated with malformations to be developed. To expand the current record of malformed Cambrian through to Devonian trilobites, we report 16 novel specimens across 12 genera from deposits spanning Australia, Bolivia, Canada, the United States, and Wales. These specimens illustrate examples of injuries potentially caused by predation, molting, and accidental injury, teratological malformations, and pathological infestation. Possible predators; explanations for developmental, genetic, and recovery issues; as well as infestations are considered. Comparison of size distributions of malformed and nonmalformed Elrathia kingii indicates that primarily the largest specimens preserve malformations. This implies that either smaller specimens fully recovered from malformations or did not survive once the malformations were incurred. Continued documentation of malformed specimens will allow larger datasets to be compiled and further promote the use of malformations in understanding trilobite paleoecology. [ABSTRACT FROM AUTHOR]

Malformed trilobites have been well documented within the arthropod fossil record and serve as valuable evidence for illustrating aspects of trilobite paleoecology associated with development, predation, and pathologies. Ongoing efforts to comprehensively document these malformations have uncovered important, often unique records for the extinct group, shedding light on post-malformation recovery processes and potential predators. A key means of recording new examples of these specimens has been the examination of historically important paleontological collections. To expand this approach, we examined the Deiss collection in the Indiana University Paleontology Collection and present four examples of malformations from Cambrian (Asaphiscus wheeleri, Dorypyge bispinosa, Wanneria walcottana), and Ordovician (Isotelus iowensis) species. These specimens reveal evidence of injuries, failed predation, and developmental complications. We explore the possible explanations for malformations and consider the current state of the art for evaluating trilobite malformations. Finally, the Deiss collection history and its ongoing contributions to Paleozoic fossils are presented. [ABSTRACT FROM AUTHOR]

Background: The rate of failed anterior cruciate ligament reconstruction (ACLR) remains high in the younger and more active patient populations. Suture tape augmentation (STA) in addition to ACLR may reduce the risk for revision surgery. Purpose/Hypothesis: The purpose of this study was to compare patient outcomes between patients who underwent primary all-inside quadrupled semitendinosus hamstring tendon autograft (QST-HTA) ACLR with and without STA. It was hypothesized that the STA cohort would demonstrate a lower incidence of subsequent revision ACLR while maintaining comparable patient-reported outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: All patients ≤40 years of age who received primary all-inside QST-HTA ACLR with and without independent STA augmentation were identified. The following validated patient-reported outcome measures (PROMs) were collected: visual analog scale for pain, Single Assessment Numeric Evaluation, Knee injury and Osteoarthritis Outcome Score subscales, and Tegner activity scale. KT-1000 arthrometer measurements were collected pre- and postoperatively. Cox proportional hazards model and nominal logistic regression analysis were used to assess additional variables associated with revision ACLR. Results: A total of 104 patients with a mean age of <22 years were included in the final data analysis (STA: 36 patients; control: 68 patients). Significantly fewer patients in the STA group sustained a graft failure necessitating revision surgery at the final follow-up (5.6% vs 24%; relative risk, 0.24 [95% CI, 0.06-0.97]; P =.017). Four-year graft survival was significantly higher in the STA group (97.2% vs 82.4%; P =.031). All PROMs significantly improved postoperatively except for Tegner levels, which decreased in both groups compared with their preinjury levels (P <.001). Return to sports was similar in both groups with >70% of patients returning to their previous level of competition. Regression analysis demonstrated increased risk for revision ACLR in younger patients, high school athletes, and those with higher postoperative activity levels. Conclusion: QST-HTA ACLR with STA was associated with reduced risk for revision ACLR compared with nonaugmented QST-HTA ACLR in this young patient population. Furthermore, the addition of suture tape did not appear to affect postoperative patient-reported and return-to-sports outcomes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed, following both single‐ and multi‐event trauma, to ascertain prevalence and course of the dissociative subtype of post‐traumatic stress disorder (PTSD‐DS) in youth; how well early PTSD‐DS predicts later PTSD; and whether dissociation accounts for unique variance in post‐traumatic stress symptoms (PTSS) and functional impairment over and above the effect of other post‐trauma cognitive processing factors and PTSS respectively. Design and Methods: This study is a secondary analysis of data from the Acute Stress Programme for Children and Teenagers study (n = 234) and the Coping in Care After Trauma study (n = 110) in which children had experienced single‐ and multi‐event trauma respectively. Results: PTSD‐DS diagnosis was common in children with PTSD regardless of trauma experienced (>39.0%). PTSD‐DS showed a similar trajectory of natural recovery to PTSD, and it was similarly predictive of later PTSD following single‐event trauma. Finally, dissociation was a significant factor in PTSS and functional impairment. Conclusions: These results should be viewed in the context of several limitations including narrow sample of participants which reduces the generalizability of results, concerns around children's ability to conceptualize challenging concepts such as dissociation and the use of self‐report measures to form diagnostic groups. The PTSD‐DS diagnosis may offer clinical utility to the extant PTSD diagnosis in children and adolescents, as dissociation has been shown to be a contributory factor in the maintenance of both PTSS and functional impairment. Further research is required to inform further editions of the DSM and other diagnostic systems. [ABSTRACT FROM AUTHOR]

The article discusses the importance of extending model-informed drug development (MIDD) by incorporating epidemiological and health economic considerations. It presents examples of extended MIDD in various therapeutic areas and emphasizes the need to go beyond safety and efficacy evaluation during regulatory approval. The article highlights the role of extended MIDD in assessing the public health impact of drugs, evaluating cost-effectiveness, and informing clinical trial design. It also discusses the application of extended MIDD in infectious diseases, cardiovascular diseases, and rare diseases. The authors emphasize the benefits of early adoption of modular approaches in drug development and suggest that continued progress in extended MIDD will enable better decision-making and optimization of drug use. [Extracted from the article]

Inkjet printing of magnetic materials has increased in recent years, as it has the potential to improve research in smart, functional materials. Magnetostriction is an inherent property of magnetic materials which allows strain or magnetic fields to be detected. This makes it very attractive for sensors in the area of structural health monitoring by detecting internal strains in carbon fibre-reinforced polymer (CFRP) composite. Inkjet printing offers design flexibility for these sensors to influence the magnetic response to the strain. This allows the sensor to be tailored to suit the location of defects in the CFRP. This research has looked into the viability of printable soft magnetic materials for structural health monitoring (SHM) of CFRP. Magnetite and nickel ink dispersions were selected to print using the JetLab 4 drop-on-demand technique. The printability of both inks was tested by selecting substrate, viscosity and solvent evaporation. Clogging was found to be an issue for both ink dispersions. Sonicating and adjusting the jetting parameters helped in distributing the nanoparticles. We found that magnetite nanoparticles were ideal as a sensor as there is more than double increase in saturation magnetisation by 49 Am2/kg and more than quadruple reduction of coercive field of 5.34 kA/m than nickel. The coil design was found to be the most sensitive to the field as a function of strain, where the gradient was around 80% higher than other sensor designs. Additive layering of 10, 20 and 30 layers of a magnetite square patch was investigated, and it was found that the 20-layered magnetite print had an improved field response to strain while maintaining excellent print resolution. SHM of CFRP was performed by inducing a strain via bending and it was found that the magnetite coil detected a change in field as the strain was applied. [ABSTRACT FROM AUTHOR]

Background: Lesotho experienced high rates of maternal (566/100,000 live births) and under-five mortality (72.9/1000 live births). A 2013 national assessment found centralized healthcare management in Ministry of Health led to fragmented, ineffective district health team management. Launched in 2014 through collaboration between the Ministry of Health and Partners In Health, Lesotho's Primary Health Care Reform (LPHCR) aimed to improve service quality and quantity by decentralizing healthcare management to the district level. We conducted a qualitative study to explore health workers' perceptions regarding the effectiveness of LPHCR in enhancing the primary health care system. Methods: We conducted 21 semi-structured key informant interviews (KII) with healthcare workers and Ministry of Health officials purposively sampled from various levels of Lesotho's health system, including the central Ministry of Health, district health management teams, health centers, and community health worker programs in four pilot districts of the LPHCR initiative. The World Health Organization's health systems building blocks framework was used to guide data collection and analysis. Interviews assessed health care workers' perspectives on the impact of the LPHCR initiative on the six-health system building blocks: service delivery, health information systems, access to essential medicines, health workforce, financing, and leadership/governance. Data were analyzed using directed content analysis. Results: Participants described benefits of decentralization, including improved efficiency in service delivery, enhanced accountability and responsiveness, increased community participation, improved data availability, and better resource allocation. Participants highlighted how the reform resulted in more efficient procurement and distribution processes and increased recognition and status in part due to the empowerment of district health management teams. However, participants also identified limited decentralization of financial decision-making and encountered barriers to successful implementation, such as staff shortages, inadequate management of the village health worker program, and a lack of clear communication regarding autonomy in utilizing and mobilizing donor funds. Conclusion: Our study findings indicate that the implementation of decentralized primary health care management in Lesotho was associated a positive impact on health system building blocks related to primary health care. However, it is crucial to address the implementation challenges identified by healthcare workers to optimize the benefits of decentralized healthcare management. [ABSTRACT FROM AUTHOR]

Rationale: Lung transplant (LTx) is a potentially lifesaving treatment option for individuals with advanced cystic fibrosis (CF), but more people with CF (PwCF) and advanced lung disease die each year than undergo transplant in the United States. Little is known about these individuals' LTx information needs and factors influencing their decision-making process related to transplant. Objectives: To examine PwCF's experiences with and preferences for provision of LTx information and to identify transplant information needs that CF clinicians are well positioned to address. Methods: We performed semistructured qualitative interviews in two separate cohorts: PwCF without LTx and PwCF with LTx between July 2019 and June 2020. Questions focused on awareness and knowledge about LTx, perspectives related to communication about transplant in the CF clinic, and experiences with LTx. Thematic analysis was used to organize the qualitative data. Exemplar quotes were chosen to llustrate domains that emerged pertaining to the research objectives. Results: Fifty-five PwCF, including 35 without LTx and 20 with LTx, participated. One-third of PwCF without LTx had normal or near-normal lung function. Key common domains among PwCF with and without LTx were identified, including information needs, connections with LTx recipients, and conversations with CF clinicians. For PwCF with and without transplant, concrete information needs were identified: success or survival, social support, surgery, recovery/pain, and quality of life post-transplant. The importance of connecting with LTx recipients to hear their stories and experiences was emphasized by both PwCF with and without transplant. Important considerations for timing and content of discussions with CF clinicians were identified, including having information presented early (before LTx referral is needed) and in limited detail at first. PwCF without LTx wanted to understand how LTx was relevant to them, with a focus on the unique experience of CF. PwCF with LTx emphasized the need for a centralized resource for LTx information. Conclusions: The findings provide content areas for CF clinicians to focus on as they proactively initiate conversations about LTx and support the development of tools to aid in discussions about LTx for PwCF. [ABSTRACT FROM AUTHOR]

Cognitive models of posttraumatic stress disorder (PTSD) highlight characteristics of trauma memories, such as disorganisation, as key mechanisms in the aetiology of the disorder. However, studies investigating trauma memory in youth have provided inconsistent findings. Research has highlighted that PTSD in youth may be accompanied by difficulties in neurocognitive functioning, potentially impacting ability to recall the trauma memory. The present study sought to investigate both trauma memory characteristics and neurocognitive functioning in youth aged 8–17 years. Youths exposed to single-event trauma, with (N = 29, Mage = 13.6, 21 female) and without (N = 40, Mage = 13.3, 21 female) a diagnosis of PTSD, completed self-report measures of trauma memory, a narrative memory task and a set of neurocognitive tests two to six months post-trauma. A group of non trauma-exposed youths (N = 36, Mage = 13.9, 27 female) were compared on narrative and neurocognitive tasks. Results indicated that trauma memories in youth with, versus without, PTSD were more sensory-laden, temporally disrupted, difficult to verbally access, and formed a more 'central' part of their identity. Greater differences were observed for self-reported memory characteristics compared to narrative characteristics. No between group differences in neurocognitive function were observed. Self-reported trauma memory characteristics highlight an important factor in the aetiology of PTSD. The observed lack of significant differences in neurocognitive ability potentially suggests that cognitive factors represent a more relevant treatment target than neurocognitive factors in single-event PTSD. Further research to understand the cognitive factors represented by self-reported trauma memory characteristics is recommended. [ABSTRACT FROM AUTHOR]

This open‐label, phase 1 study was conducted with healthy adult participants to evaluate the potential drug‐drug interaction between rilzabrutinib and quinidine (an inhibitor of P‐glycoprotein [P‐gp] and CYP2D6) or rifampin (an inducer of CYP3A and P‐gp). Plasma concentrations of rilzabrutinib were measured after a single oral dose of rilzabrutinib 400 mg administered on day 1 and again, following a wash‐out period, after co‐administration of rilzabrutinib and quinidine or rifampin. Specifically, quinidine was given at a dose of 300 mg every 8 hours for 5 days from day 7 to day 11 (N = 16) while rifampin was given as 600 mg once daily for 11 days from day 7 to day 17 (N = 16) with rilzabrutinib given in the morning of day 10 (during quinidine dosing) or day 16 (during rifampin dosing). Quinidine had no significant effect on rilzabrutinib pharmacokinetics. Rifampin decreased rilzabrutinib exposure (the geometric mean of Cmax and AUC0‐∞ decreased by 80.5% and 79.5%, respectively). Single oral doses of rilzabrutinib, with or without quinidine or rifampin, appeared to be well tolerated. These findings indicate that rilzabrutinib is a substrate for CYP3A but not a substrate for P‐gp. [ABSTRACT FROM AUTHOR]

Background: Complex PTSD (CPTSD) is a relatively new diagnosis. The objective of the present study was to investigate how trauma characteristics, comorbid psychopathology and cognitive and social factors experienced by children and adolescents with a posttraumatic stress disorder (PTSD) diagnosis following exposure to multiple traumatic events differs between those who meet the criteria for CPTSD and those who do not. Method: The present research used baseline data from the DECRYPT trial (BMJ Open, 2021, 11, e047600). Participants (n = 120) were aged 8–17 years and had exposure to multiple traumas and a PTSD diagnosis. The data collected comprised self‐report and parent/caregiver‐report questionnaires and interviews. Three primary analyses were conducted, comparing number of trauma types, prevalence of sexual trauma and prevalence of intrafamilial abuse between the CPTSD and PTSD‐only groups. A range of comorbid psychopathology and cognitive and social factors were compared between the groups in an exploratory secondary analysis. All analyses were preregistered. Results: The CPTSD group (n = 72, 60%) had a significantly higher frequency of sexual trauma than the PTSD‐only group (n = 48, 40%). The groups did not significantly differ on number of trauma types or prevalence of intrafamilial abuse. From the secondary analysis, the CPTSD group were found to have significantly higher scores on measures of negative post‐traumatic cognitions, depression and panic. These results were replicated in correlation analyses using a continuous measure of CPTSD symptoms. Conclusions: A large proportion of youth exposed to multiple traumatic events met criteria for CPTSD. Sexual trauma appears to be related to CPTSD symptoms. Youth with CPTSD appear to have greater severity of comorbid depression and panic symptoms, as well as more negative post‐traumatic cognitions. Further investigation could focus on the directionality and mechanisms for these associations. [ABSTRACT FROM AUTHOR]

Background: The potential intra-articular effects of ≥1 year after anterior cruciate ligament reconstruction (ACLR) with independent suture tape augmentation (STA) are not fully understood. Purpose: To investigate whether incorporating suture tape in an all–soft tissue quadriceps tendon autograft (QTA) ACLR leads to satisfactory patient outcomes while having no intra-articular side effects as determined by magnetic resonance imaging (MRI). Study Design: Case series; Level of evidence, 4. Methods: Included were 25 patients with a mean age of 19.9 years (95% CI, 17.3-22.5 years) who underwent QTA ACLR with STA between 2016 and 2019. All patients underwent MRI at ≥1 year postoperatively and had at least a 2-year follow-up (mean, 28 months [95% CI, 26.5-29.5 months]) that included physical examination with anterior laxity testing with KT-1000 arthrometer, radiographs, and patient-reported outcome measures (PROMs). At the final follow-up, the minimal clinically important difference (MCID) and the Patient Acceptable Symptom State (PASS) for applicable PROMs were applied to each patient. Postoperative graft and joint integrity were assessed using the Howell classification and the MRI Osteoarthritis Knee Score (MOAKS) joint effusion/synovitis grade. The Mann-Whitney U test for continuous variables and the chi-square or the Fisher exact test for categorical variables were used for statistical analyses. Results: The MRI assessment of the grafts demonstrated intact grafts in all patients. Overall, 96% of patients demonstrated grades 0 or 1 MOAKS for joint effusion/synovitis. All patient outcomes significantly improved from preoperatively to the final follow-up (P < .001), except for the Marx score, which decreased significantly (14.2 [95% CI, 12.7-15.8] vs 9.72 [95% CI, 7.3-12.2]; P = .0014). At least 68% of the patients achieved the MCID threshold, and 92% achieved the PASS threshold for all applicable PROMs. Conclusion: QTA ACLR with STA did not demonstrate adverse intra-articular changes on MRI at ≥1 year postoperatively. In addition, STA did not appear to negatively affect PROMs. [ABSTRACT FROM AUTHOR]

Background: While posterior medial meniscus root (PMMR) techniques have evolved, there remains a need to both optimize repair strength and improve resistance to cyclic loading. Hypothesis: Adjustable tensioning would lead to higher initial repair strength and reduce displacement with cyclic loading compared with previously described transtibial pull-out repair (TPOR) fixation techniques. Study Design: Controlled laboratory study. Methods: A total of 56 porcine medial menisci were used. Eight intact specimens served as a control for the native meniscus. For the others, PMMR tears were created and repaired with 6 different TPOR techniques (8 in each group). Fixed PMMR repairs were executed using 4 different suture techniques (two No. 2 cinch sutures, two cinch tapes, two No. 2 simple sutures, and two No. 2 sutures in a Mason-Allen configuration) all tied over a cortical button. Adjustable PMMR repairs using Mason-Allen sutures were fixed with an adjustable soft tissue anchor fixation tensioned at either 80 N or 120 N. The initial force, stiffness, and relief displacement of the repairs were measured after fixation. Repair constructs were then cyclically loaded, with cyclic displacement and stiffness measured after 1000 cycles. Finally, the specimens were pulled to failure. Results: The PMMR repaired with the 2 cinch sutures fixed technique afforded the lowest (P < .001) initial repair load, stiffness, and relief displacement. The adjustable PMMR repairs achieved a higher initial repair load (P < .001) and relief displacement (P < .001) than all fixed repairs. The 2 cinch sutures fixed technique showed an overall higher cyclic displacement (P < .028) and was completely loose compared with the native meniscus functional zone. Repairs with adjustable intratunnel fixation showed displacement with cyclic loading similar to the native meniscus. With cyclic loading, the Mason-Allen adjustable repair with 120 N of tension showed less displacement (P < .016) than all fixed repairs and a stiffness comparable to the fixed Mason-Allen repair. The fixed Mason-Allen technique demonstrated a higher ultimate load (P < .007) than the adjustable Mason-Allen techniques. All repairs were less stiff, with lower ultimate failure loads, than the native meniscus root attachment (P < .0001). Conclusion: Adjustable TPOR led to considerably higher initial repair load and relief displacement than other conventional fixed repairs and restricted cyclic displacement to match the native meniscus function. However, the ultimate failure load of the adjustable devices was lower than that of a Mason-Allen construct tied over a cortical button. All repair techniques had a significantly lower load to failure than the native meniscus root. Clinical Relevance: Knotless adjustable PMMR repair based on soft anchor fixation results in higher tissue compression and less displacement, but the overall clinical significance on healing rates remains unclear. [ABSTRACT FROM AUTHOR]

Insomnia and poor sleep are associated with an increased risk of developing cardiovascular disease (CVD) and its precursors, including hypertension. In 2022, the American Heart Association (AHA) added inadequate sleep to its list of health behaviors that increase the risk for CVD. It remains unknown, however, whether the successful treatment of insomnia and inadequate sleep can reduce heightened CVD risk. SLEEPRIGHT is a single‐site, prospective clinical trial designed to evaluate whether the successful treatment of insomnia results in improved markers of CVD risk in patients with untreated hypertension and comorbid insomnia disorder. Participants (N = 150) will undergo baseline assessments, followed by a 6‐week run‐in period after which they will receive cognitive behavior therapy for insomnia (CBT‐I), comprised of 6 hourly sessions with an experienced CBT‐I therapist over a 6‐week period. In addition to measures of insomnia severity, as well as both subjective and objective measures of sleep, the primary outcome measures are nighttime blood pressure (BP) and BP dipping assessed by 24‐h ambulatory BP monitoring (ABPM). Secondary outcomes include several CVD risk biomarkers, including clinic BP, lipid profile, vascular endothelial function, arterial stiffness, and sympathetic nervous system (SNS) activity. Data analysis will evaluate the association between improvements in insomnia and sleep with primary and secondary CVD risk biomarker outcomes. The SLEEPRIGHT trial (ClinicalTrials.Gov NCT04009447) will utilize CBT‐I, the current gold standard treatment for insomnia disorder, to evaluate whether reducing insomnia severity and improving sleep are accompanied by improved biomarkers of CVD risk in patients with untreated hypertension. [ABSTRACT FROM AUTHOR]

In England, children and adolescents with depression can seek treatment from specialist mental health services. We know little about how they journey through these services, or whether healthcare providers collect sufficient data to accurately appraise this. We aimed to summarise the child and adolescent depression pathway for two healthcare providers. This cohort study used de-identified electronic health records extracted from Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) and South London and Maudsley NHS Foundation Trust (SLaM). We identified referrals between 2015 and 2019 during which the referred patient received their first depression diagnosis aged < 18 years. We described patient demographic and clinical characteristics, and features of the referral. In total, n = 296 (CPFT) and n = 2502 (SLaM) patients had a referral which met eligibility criteria. In both sites, patients were more frequently female (CPFT 79.3%; SLaM 69.3%) and White ethnicity (CPFT 88.9%; SLaM 57.9%) as compared to respective population estimates for the Trusts' catchment areas. Patients typically received their first depression diagnosis during adolescence (median ages 16 in CPFT and 15 in SLaM). The most common comorbidity was anxiety disorder. Referrals were usually routine, to community teams specialising in the child age group. Commonly mentioned interventions included antidepressant medication, cognitive behavioural therapy, and dialectical behaviour therapy. However, pathways varied within and between sites, and the quality and consistency of some data was poor. These findings provide an overview of service pathways experienced by children and adolescents with depression, but also highlight that pathways can vary according to individual need and healthcare provider. More systematic collection of some data, and standardisation in record systems used by different providers, would be beneficial. [ABSTRACT FROM AUTHOR]

Background: Some human studies have identified infection with cytomegalovirus (CMV), a member of the alpha herpesvirus family, as a risk factor for Alzheimer's disease and related dementias (ADRD). To our knowledge, no studies have evaluated associations of CMV seropositivity with plasma biomarkers of ADRD risk in middle-aged adults. Objective: In participants recruited for an exercise study, we evaluated cross-sectional associations of CMV seropositivity with: Aβ42/Aβ40 ratio, a low ratio suggestive of central nervous system Aβ accumulation; glial fibrillary acidic protein (GFAP), a measure of neuroinflammation; and neurofilament light (NfL), a measure of neurodegeneration. Methods: Anti-CMV IgG was quantified by ELISA. Plasma ADRD biomarkers were quantified using the ultrasensitive SIMOA assay. We used linear regression to evaluate associations of CMV seropositivity with the ADRD biomarkers, adjusting for age, sex, and race (n = 303; Age = 55.7±9.2 years). For ADRD biomarkers significantly associated with CMV seropositivity, we evaluated continuous associations of anti-CMV IgG levels with the ADRD biomarkers, excluding CMV seronegative participants. Results: 53% of participants were CMV seropositive. CMV seropositivity was associated with a lesser Aβ42/Aβ40 ratio (β=–3.02e–03 95% CI [–5.97e–03, –7.18e–05]; p = 0.045). In CMV seropositive participants, greater anti-CMV IgG levels were associated with a lesser Aβ42/Aβ40 ratio (β=–4.85e–05 95% CI[–8.45e–05, –1.25e–05]; p = 0.009). CMV seropositivity was not associated with plasma GFAP or NfL in adjusted analyses. Conclusions: CMV seropositivity was associated with a lesser plasma Aβ42/Aβ40 ratio. This association may be direct and causally related to CMV neuro-cytotoxicity or may be indirect and mediated by inflammatory factors resulting from CMV infection burden and/or the immune response. [ABSTRACT FROM AUTHOR]

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The Bear Gulch Limestone houses a diverse, exceptionally preserved marine fauna from the early Carboniferous. A wealth of vertebrate and invertebrate forms has previously been recorded from this deposit, including fish, annelids, and several arthropods. To expand the record of Bear Gulch marine arthropods, a new enigmatic, possibly blind euchelicerate, Titanoprosoma edgecombei, gen. et sp. nov., is described. The new euchelicerate taxon displays a hypertrophied, ovate, and structureless prosoma—a morphology unique among marine euchelicerates. We explore how the large prosoma and lack of ocular structures reflect possible adaptations to an infaunal, burrowing lifestyle. This species represents the fourth euchelicerate genus described from the Bear Gulch Limestone, further highlighting the impressive disparity of marine arthropods preserved in the deposit. The addition of novel invertebrate forms found in previously unknown museum material suggests that the Bear Gulch Limestone likely houses a still undocumented diversity of Carboniferous arthropods. [ABSTRACT FROM AUTHOR]

Low self‐esteem can impair daily functioning and is a risk or maintenance factor for several mental health problems. Sexual minority young adults, for example, those identifying as lesbian, gay or bisexual, on average have lower self‐esteem than their heterosexual peers. Compassion‐based interventions for low self‐esteem might be especially beneficial for sexual minority young adults, whose higher levels of shame and self‐criticism are likely to be contributing to maintenance of their low self‐esteem. This study explored the acceptability, feasibility and preliminary efficacy of a new compassion‐based cognitive behavioural intervention for low self‐esteem tailored to sexual minority young adults. Participants were a community sample of 24 sexual minority young adults aged 16–24 experiencing clinically significant low self‐esteem. An uncontrolled pre‐/post‐design was used with qualitative feedback and quantitative outcomes. Self‐report standardised measures were completed at baseline, pre‐intervention, intervention mid‐point, post‐intervention and 2‐month follow up. Preliminary efficacy was examined through post‐intervention changes in self‐esteem, functioning, anxiety and depression. Potential mechanisms of change were examined through changes in self‐compassion, self‐criticism and unhelpful coping responses to minority stress. Results showed good acceptability and feasibility and preliminary evidence of intervention efficacy for improving self‐esteem, functioning, depression and anxiety. There was evidence for improvement in self‐compassion and reduction in self‐criticism, and these constructs could be investigated in future studies as treatment mediators. Randomised controlled studies are needed to further examine efficacy of the intervention. [ABSTRACT FROM AUTHOR]

Interventions to preserve functional independence in older adults are critically needed to optimize ‘successful aging’ among the large and increasing population of older adults in the United States. For most aging adults, the management of chronic diseases is the most common and impactful risk factor for loss of functional independence. Chronic disease management inherently involves the learning and adaptation of new behaviors, such as adopting or modifying physical activity habits and managing weight. Despite the importance of chronic disease management in older adults, vanishingly few individuals optimally manage their health behavior in the service of chronic disease stabilization to preserve functional independence. Contemporary conceptual models of chronic disease management and health habit theory suggest that this lack of optimal management may result from an underappreciated distinction within the health behavior literature: the behavioral domains critical for initiation of new behaviors (Initiation Phase) are largely distinct from those that facilitate their maintenance (Maintenance Phase). Psychological factors, particularly experiential acceptance and trait levels of openness are critical to engagement with new health behaviors, willingness to make difficult lifestyle changes, and the ability to tolerate aversive affective responses in the process. Cognitive factors, particularly executive function, are critical to learning new skills, using them effectively across different areas of life and contextual demands, and updating of skills to facilitate behavioral maintenance. Emerging data therefore suggests that individuals with greater executive function are better able to sustain behavior changes, which in turn protects against cognitive decline. In addition, social and structural supports of behavior change serve a critical buffering role across phases of behavior change. The present review attempts to address these gaps by proposing a novel biobehavioral intervention framework that incorporates both individual-level and social support system-level variables for the purpose of treatment tailoring. Our intervention framework triangulates on the central importance of self-regulatory functioning, proposing that both cognitive and psychological mechanisms ultimately influence an individuals’ ability to engage in different aspects of self-management (individual level) in the service of maintaining independence. Importantly, the proposed linkages of cognitive and affective functioning align with emerging individual difference frameworks, suggesting that lower levels of cognitive and/or psychological flexibility represent an intermediate phenotype of risk. Individuals exhibiting selfregulatory lapses either due to the inability to regulate their emotional responses or due to the presence of executive functioning impairments are therefore the most likely to require assistance to preserve functional independence. In addition, these vulnerabilities will be more easily observable for individuals requiring greater complexity of self-management behavioral demands (e.g. complexity of medication regimen) and/or with lesser social support. Our proposed framework also intuits several distinct intervention pathways based on the profile of selfregulatory behaviors: we propose that individuals with intact affect regulation and impaired executive function will preferentially respond to ‘top-down’ training approaches (e.g., strategy and process work). Individuals with intact executive function and impaired affect regulation will respond to ‘bottom-up’ approaches (e.g., graded exposure). And individuals with impairments in both may require treatments targeting caregiving or structural supports, particularly in the context of elevated behavioral demands. [ABSTRACT FROM AUTHOR]

Biomineralised remains of trilobites provide important insight into the evolutionary history of a diverse, extinct group of arthropods. Their exoskeletons are also ideal for recording malformations, including evidence of post-injury repair. Re-examination of historic collections and the study of new specimens is important for enhancing knowledge on trilobite malformations across this diverse clade. To expand the records of these abnormalities and present explanations for their formation, we document eight malformed trilobite specimens, as well as one carcass, housed within the Commonwealth Palaeontological Collection at Geoscience Australia in Canberra. We present examples of Asthenopsis, Burminresia, Centropleura, Coronocephalus, Dolicholeptus, Galahetes, Papyriaspis, and Xystridura from Cambrian, Ordovician, and Silurian deposits of Australia. Most of the malformed specimens show W-, U-, or L-shaped indentations that reflect injuries from either failed predation or complications during moulting, and a mangled carcass is ascribed to either successful predation or post-mortem scavenging. We also uncover examples of teratologies, such as bifurcated pygidial ribs and pygidial asymmetry, in addition to evidence of abnormal recovery (i.e., fusion of thoracic segments) from a traumatic incident. [ABSTRACT FROM AUTHOR]

Background: Recently, the posterior horn lateral meniscal oblique radial tear (LMORT) was identified in 12% of acute anterior cruciate ligament (ACL) injuries. However, patient-reported outcomes for repair of this relatively common tear have not been reported. Purpose: To determine the minimum 2-year functional outcomes after LMORT repair at the time of ACL reconstruction (ACLR) compared to a matched cohort of patients who underwent isolated ACLR (iACLR). Study Design: Cohort study; Level of evidence, 3. Methods: Included were 100 patients (mean age at surgery, 21 years; range, 13-45 years) who underwent primary ACLR between 2010 and 2018. The mean follow-up period was 4.1 ± 2.0 years (range, 2.0-9.2 years). A total of 50 patients with surgically repaired LMORT type 3 or type 4 lesions, defined as partial or complete tears >10 mm from the root (LMORT group) were matched 1:1 based on age, date of surgery, and graft choice with 50 patients who underwent iACLR (iACLR group). The postoperative outcomes were compared between groups using the International Knee Documentation Committee subjective score (sIKDC) and the Tegner activity scale. An updated medical history was obtained via the electronic medical record to determine any subsequent complications and reoperations. Results: There was 1 ACL graft failure in each group as well as 5 (10%) reoperations per group. None of the patients in the LMORT group necessitated a lateral meniscal revision repair or partial meniscectomy. The LMORT and iACLR groups reported comparable sIKDC scores (92.5 ± 6.8 vs 91.9 ± 8.2, respectively; P =.712) as well as Tegner scores (6.7 ± 1.8 vs 6.6 ± 1.8, respectively; P =.910) at final follow-up. No failures of the LMORT repairs were reported. Conclusion: The study findings demonstrated that reoperations, graft failure rates, patient-reported outcomes, and patient activity levels at ≥2 years after type 3 and 4 LMORT repairs at the time of ACLR compared favorably with those of a matched cohort of patients who underwent iACLR with intact meniscus. [ABSTRACT FROM AUTHOR]

Background: Lateral meniscal oblique radial tears (LMORTs) are the most common type of lateral meniscal tears and occur concomitantly with anterior cruciate ligament (ACL) tears in up to 12% of cases. Four types of LMORTs have been classified in the literature based on proximity to the meniscal root and extent of the tear. Type 1 and 2 LMORTs represent partial and complete posterior root tears less than 10 mm from the root insertion. Type 3 and 4 LMORTs are partial and complete posterior radial meniscus tears greater than 10 mm from the root insertion. Indications: Type 3 and 4 LMORTs can and should be addressed with an all-inside side-to-side repair at the time of ACL reconstruction. LMORTs that are not repaired at the time of ACL reconstruction can contribute to persistent instability and meniscal extrusion. Technique Description: Diagnostic arthroscopy is performed to evaluate the posterior aspects of both the medial and lateral meniscus. The medial leaflet is commonly flipped into the notch and scarred to ACL remnant. After identifying and isolating the medial leaflet, an arthroscopic suture passer is used to pass a suture from inferior to superior through the medial leaflet. A second suture is passed from inferior to superior through the lateral leaflet. This is used to shuttle the suture pass through the medial leaflet to the bottom of the meniscus, where it can be tied in a horizontal mattress fashion. The sutures are tied down with aide of an arthroscopic knot pusher. A second set of sutures is passed and used to shuttle a second suture that would be tied posterior to the first suture, again in a horizontal mattress fashion. This allows reduction of the fragments in apposition across the tear. Postoperatively, patients are allowed range of motion from 0° to 90° and to toe touch weightbearing for the first 4 weeks. Patients are advanced to weightbearing as tolerated at 5 weeks. Typical return to sport ranges from 6 to 9 months postoperatively. Results: Results have been published for 2-year outcomes of type 3 and 4 LMORT repairs and have demonstrated persistent improved patient-reported outcomes as well as healing rates that are greater than 80% and in some series approach nearly 100%. Discussion/Conclusion: Arthroscopic all-inside side-to-side surgical repair is a durable and reliable treatment option for patients presenting for ACL reconstruction with concomitant type 3 or 4 LMORT. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]

Public dental insurance programs for children aim to provide access to care, but barriers remain that preclude care delivery. Understanding these barriers is an important health policy concern. A telephone audit sought to ascertain availability of oral health care for children in dental offices eligible to bill Medicaid. Female callers posing as mothers called eligible offices requesting appointments. In this cross-over design, offices were randomized to public or private insurance for initial calls and then to the other condition after a washout period. Using mixed models, privately insured patients had 5.9 times (95% CI, 4.55 to 7.69) greater odds of obtaining an appointment than Medicaid patients. Compared with patients in Cook County, suburban patients had slightly better odds, whereas nonurban patients in larger and smaller rural counties had lower odds of success. Medicaid compares poorly with private insurance for providing access to pediatric oral health care. Regardless of insurance conditions, access is poor in less urban environments compared with metropolitan communities. Even Medicaid-enrolled dental practices limit the care they extend to insured children. Providing Medicaid by itself cannot overcome large oral health care access disparities, which are greatest in rural communities. [ABSTRACT FROM AUTHOR]

Melanie Fennell's (1997) seminal cognitive approach to low self-esteem was published in Behavioural and Cognitive Psychotherapy. The current paper proposes a refined model, drawing on social theories, and research with people with socially devalued characteristics. This model emphasises how self-esteem relates to perceptions of one's value in the eyes of others. It is proposed that core beliefs typical of low self-esteem relate to one's value in relation to personal adequacy (e.g. having worth or status) and/or to social connection (e.g. being liked, loved, accepted or included). In each of these value domains, beliefs about both the self (e.g. 'I am a failure', 'I am unlovable') and others (e.g. 'Others look down on me', 'Others don't care about me') are considered important. The model suggests that everyone monitors their value but in people with low self-esteem, cognitive biases associated with underlying beliefs occur. In the context of trigger situations, this results in a greater likelihood of negative appraisals of perceived threat to one's value. Such appraisals activate underlying negative beliefs, resulting in negative mood (e.g. low mood, anxiety, shame, disgust) and other responses that maintain low self-esteem. Responses which can be used excessively or in unhelpful ways include (a) corrective behaviours; (b) compensatory strategies; (c) increased value monitoring; (d) safety-seeking behaviours; (e) rumination; (f) unhelpful mood regulation responses. These responses can adversely impact daily functioning or health, having the counterproductive effect of maintaining negative beliefs about one's value. Examples are provided for low self-esteem in lesbian, gay and bisexual individuals. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic has resulted in heightened moral distress among health care workers (HCWs) worldwide. Past research has shown that effective leadership may mitigate potential for the development of moral distress. However, no research to date has considered the mechanisms by which leadership might have an influence on moral distress. We sought to evaluate longitudinally whether Canadian HCWs' perceptions of workplace support and ethical work environment would mediate associations between leadership and moral distress. Methods: A total of 239 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in a longitudinal online survey. Participants completed measures of organizational and supervisory leadership at baseline and follow-up assessments of workplace support, perceptions of an ethical work environment, and moral distress. Results: Associations between both organizational and supervisory leadership and moral distress were fully mediated by workplace supports and perceptions of an ethical work environment. Discussion: To ensure HCW well-being and quality of care, it is important to ensure that HCWs are provided with adequate workplace supports, including manageable work hours, social support, and recognition for efforts, as well as an ethical workplace environment. [ABSTRACT FROM AUTHOR]

Injured trilobites present insight into how a completely extinct group of arthropods responded to traumatic experiences, such as failed predation and moulting complications. These specimens are therefore important for more thoroughly understanding the Paleozoic predator-prey systems that involved trilobites. To expand the record of injured trilobites, we present new examples of injured Ogygopsis klotzi and Olenoides serratus from the Campsite Cliff Shale Member of the Burgess Shale Formation (Cambrian, Miaolingian, Wuliuan), Paradoxides (Paradoxides) paradoxissimus gracilis from the Jince Formation (Cambrian, Miaolingian, Drumian), Ogygiocarella angustissima from the Llanfawr Mudstones Formation (Middle-Late Ordovician, Darriwilian-Sandbian), and Ogygiocarella debuchii from the Meadowtown Formation, (Middle-Late Ordovician, Darriwilian-Sandbian). We consider the possible origins of these malformations and conclude that most injuries reflect failed predation. Within this framework, possible predators are presented, and we uncover a marked shift in the diversity of animals that targeted trilobites in the Ordovician. We also collate other records of injured Ogygo. klotzi and Ol. serratus, and Ogygi. debuchii, highlighting that these species are targets for further understanding patterns and records of trilobite injuries. [ABSTRACT FROM AUTHOR]

Birding is one of the most popular recreational activities, but bird populations have been declining worldwide. Understanding how much people benefit from local bird populations levels, species richness and their preferences can help inform bird conservation management. This paper uses eBird data and random utility models to assess the birders' preferences and welfare for trips to local areas. The sample eBird citizen science data includes 35,656 trips by 290 individual birders to 1227 unique birding hotspots in Alberta, Canada. The economic value of seeing one additional bird species during a trip is estimated to be $0.68 on average. We estimated a nonlinear relationship between the utility and number of bird species suggesting satiation in recreation preferences, and the highest MWTP is estimated to be in the summer and fall seasons. Bird species at risk, based on Alberta's strategy for the management of species at risk, are valued almost ten times higher as seeing other types of bird species. We also estimate individualized choice models and find that preference for species richness is heterogeneous across birders. Results of a combinatorial test find that the individualized choice models produce average welfare estimates that are 67% higher than the single model but the difference is not statistically significant. The members of eBird represent a convenience sample that may not constitute the general population. Thus along with proper weighting, these benefit estimates produced in this research can help inform future bird conservation management decisions including alternative funding mechanisms. [ABSTRACT FROM AUTHOR]

Background: A knotless, tensionable primary anterior cruciate ligament (ACL) repair system preloaded with an internal brace has been released. Currently, there is no biomechanical data on the stabilization and gap formation behavior of the adjustable system when compared with fixed repairs in human ACL tissue. Hypothesis: That knotless adjustable suture repair with an internal brace would provide overall higher construct stability and greater load share on the ACL with less gap formation compared with fixed repair. Study Design: Controlled laboratory study. Methods: Human cadaveric knees were utilized for internal braced ACL repair constructs (each group n = 16). Two fixed groups consisting of a single-cinch loop (SCL), cortical button (SCL group), and knotless suture-anchor (anchor group) were compared with an SCL-adjustable loop device (SCL-ALD) group. Testing was performed at 4 different peak loads (50, 150, 250, 350 N) over 4000 cycles at 0.75 Hz including suture repair preconditioning (10 cycles at 0.5 Hz) for SCL-ALD. Specimens were ultimately pulled to failure with a cut internal brace. The final loading situation of the construct and ACL repair with gap formation and ultimate strength were evaluated. Results: Peak elongation at various peak loads showed a significantly higher (P <.001) stabilization of SCL-ALD when compared with both fixed groups. There was a significantly higher (P <.001) load share of SCL-ALD, especially at lower loads (48% of 50 N), and the gap formation remained restricted up to 250 N. With only a little load share on the fixed constructs (<6%) at lower loads (50, 150 N), gap formation in these groups started at a load of 150 N, leading to significantly higher gaps (P <.001). The ultimate failure load for SCL-ALD and anchor groups was significantly increased (P <.001) as compared with SCL. The stiffness of SCL-ALD (62.9 ± 10.6 N/mm) was significantly increased (P <.001). Conclusion: Internal braced knotless adjustable fixation for ACL repair with preconditioning of the suture repaired ligament increased the overall stabilization with higher load share on the ACL and restricted gap formation (<0.5 mm up to 350 N) compared with fixed suture repair. All internal braced repairs restored stability according to native ACL function. Clinical Relevance: Adjustable ACL repair improved the mechanical characteristics and reduced gap formation, but the overall clinical significance on healing remains unclear. [ABSTRACT FROM AUTHOR]

Background: Little is known about the stability of adjustable-loop devices (ALDs) for anterior cruciate ligament (ACL) reconstruction (ACLR). Purpose: To evaluate the stabilization behavior of 3 different types of ALDs for all-inside ACLR in a full-construct surgical technique-based manner. Study Design: Controlled laboratory study. Methods: The femoral and tibial devices of Ultrabutton (Smith & Nephew), Infinity (Conmed), and TightRope II (Arthrex) were applied to quadrupled bovine tendon grafts (n = 8 each) with tibial-sided traction applied (350 N) for graft tensioning in a simulated fully extended knee. Knotless femoral graft fixation was based on either a suture-locking device (SLD; Ultrabutton), button-locking device (BLD; Infinity), or dual-locking device (DLD; TightRope II). All constructs were progressively loaded (50 N/500 cycles) from 50 to 300 N for 3000 cycles (0.75 Hz), including complete unloading situations and pull to failure (50 mm/min). Construct elongation, stiffness, and ultimate load were analyzed. Results: BLD showed significantly greater initial elongation (-2.69 ± 0.15 mm) than DLD (-3.19 ± 0.21 mm; P <.001) but behaved similarly to SLD (-2.93 ± 0.23 mm). While DLD and SLD had the smallest initial elongation at the same significance level, they behaved opposite to each other with gradually increasing peak loading. At the end of testing, DLD had the lowest (-0.64 ± 0.32 mm) and SLD the highest (3.41 ± 1.01 mm) total elongation (P <.003 for both). SLD displayed significantly higher dynamic elongation (6.34 ± 0.23 mm) than BLD (3.21 ± 0.61 mm) and DLD (2.56 ± 0.31 mm) (P <.001 for both). The failure load of BLD (865.0 ± 183.8 N) was significantly lower (P <.026) compared with SLD and DLD (>1000 N). The predominant failure mode was suture rupture and tibial bone breakage with button subsidence (SLD, n = 4). No significant difference in stiffness between constructs was found. Conclusion: While DLD successfully restricted critical construct elongation, BLD partially and SLD completely exceeded the clinical failure threshold (>3 mm) of plastic elongation with loop lengthening during increasing cyclic peak loading with complete unloading. Higher failure loads of SLD and DLD implants (>1000 N) were achieved at similar construct stiffness to BLD. Clinical Relevance: A detailed biomechanical understanding of the stabilization potential is pertinent to the continued evolution of ALDs to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

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Collaboration between the arts and health sectors is gaining momentum. Artists are contributing significantly to public health efforts such as vaccine confidence campaigns. Artists and the arts are well positioned to contribute to the social conditions needed to build trust in the health sector. Health professionals, organizations, and institutions should recognize not only the power that can be derived from the insights, artefacts, and expertise of artists and the arts to create the conditions that make trust possible. The health sector must also recognize that, while it can gain much from partnership with artists, artists risk much—namely, the public's trust—when they are in such partnerships. This essay unpacks these claims and considers the care and ethical considerations that must be brought to these partnerships to yield constructive pathways for ethical collaboration as well as for both establishing public trust and continuing to hold the health care profession accountable for becoming more trustworthy. [ABSTRACT FROM AUTHOR]

We provide a new framework for using text as data in empirical models. The framework identifies salient information in unstructured text that can control for multidimensional heterogeneity among assets. We demonstrate the efficacy of the framework by reexamining principal-agent problems in residential real estate markets. We show that the agent-owned premiums reported in the extant literature dissipate when the salient textual information is included. The results suggest the previously reported agent-owned premiums suffer from an omitted variable bias, which prior studies incorrectly ascribed to market distortions associated with asymmetric information. (JEL D82, G14, R00) Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online. [ABSTRACT FROM AUTHOR]

CD40 is a central costimulatory receptor implicated in productive antitumor immune responses across multiple cancers, including bladder cancer. Despite strong preclinical rationale, systemic administration of therapeutic agonistic antibodies targeting the CD40 pathway has demonstrated dose-limiting toxicities with minimal clinical activity, emphasizing an important need for optimized CD40-targeted approaches, including rational combination therapy strategies. Here, we describe a role for the endogenous IL-15 pathway in contributing to the therapeutic activity of CD40 agonism in orthotopic bladder tumors, with upregulation of transpresented IL-15/IL-15Rα surface complexes, particularly by cross-presenting conventional type 1 DCs (Dendritic Cells), and associated enrichment of activated CD8 T cells. In bladder cancer patient samples, we identify DCs as the primary source of IL-15, although they lack high levels of IL-15Rα at baseline. Using humanized immunocompetent orthotopic bladder tumor models, we demonstrate the ability to therapeutically augment this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer. Collectively, these data reveal an important role for IL-15 in mediating antitumor CD40 agonist responses in bladder cancer and provide key proof-of-concept for combined use of Fc-optimized anti-CD40 agonist antibodies and agents targeting the IL-15 pathway. These data support expansion of ongoing clinical studies evaluating anti-CD40 agonist antibodies and IL-15-based approaches to develop combinations of these promising therapeutics for the treatment of patients with bladder cancer. [ABSTRACT FROM AUTHOR]

Black men are disproportionately impacted by oral and pharyngeal cancer (OPC) mortality. This is in part due to a lack of information received about OPCs and their associated risk factors during health encounters. Discussions between dentists and Black men may improve Black men's knowledge, screening, and treatment uptake. Yet, dentists do not commonly communicate with Black men about OPCs due to their own discomfort. This paper describes the protocol for our research project, which proposes an initiative, grounded in community-based participatory research, to adapt a culturally-specific OPC communication tool. This tool will be adapted using a mixed-methods approach to assess the knowledge, attitudes, and experiences of Black men discussing OPCs and associated risk factors with dental providers. The tool will then be assessed for feasibility and acceptability among Black men, as well as dental students and dental providers in community-based clinical settings. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants (≥1 to ≤12 months) and neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to ≤36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. This contrasts with the findings of the previous RSV-A adult challenge study where significant antiviral activity was noted, without incidence of neutropenia. Trial registration ClinicalTrials.gov Identifier: NCT02202356 (phase 1b); NCT03333317 (phase 2b). [ABSTRACT FROM AUTHOR]

Frailty, measured as a single construct, is associated variably with poor outcomes before and after lung transplantation. The usefulness of a comprehensive frailty assessment before transplantation is unknown. How are multiple frailty constructs, including phenotypic and cumulative deficit models, muscle mass, exercise tolerance, and social vulnerabilities, measured before transplantation, associated with short-term outcomes after lung transplantation? We conducted a retrospective cohort study of 515 lung recipients who underwent frailty assessments before transplantation, including the short physical performance battery (SPPB), transplant-specific frailty index (FI), 6-min walk distance (6MWD), thoracic sarcopenia, and social vulnerability indexes. We tested the association between frailty measures before transplantation and outcomes after transplantation using logistic regression to model 1-year survival and zero-inflated negative binomial regression to model hospital-free days (HFDs) in the first 90 days after transplantation. Adjustment covariates included age, sex, native lung disease, transplantation type, lung allocation score, BMI, and primary graft dysfunction. Before transplantation, 51.3% of patients were frail by FI (FI ≥ 0.25) and no patients were frail by SPPB. In multivariate adjusted models that also included FI, SPPB, and 6MWD, greater frailty by FI, but not SPPB, was associated with fewer HFDs (–0.006 per 0.01 unit worsening; 95% CI, –0.01 to –0.002 per 0.01 unit worsening) among discharged patients. Greater SPPB deficits were associated with decreased odds of 1-year survival (OR, 0.51 per 1 unit worsening; 95% CI, 0.28-0.93 per 1 unit worsening). Correlation among frailty measurements overall was poor. No association was found between thoracic sarcopenia, 6MWD, or social vulnerability assessments and short-term outcomes after lung transplantation. Both phenotypic and cumulative deficit models measured before transplantation are associated with short-term outcomes after lung transplantation. Cumulative deficit measures of frailty may be more relevant in the first 90 days after transplantation, whereas phenotypic frailty may have a stronger association with 1-year survival. [Display omitted] [ABSTRACT FROM AUTHOR]