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Tissue growth and remodeling (GR) is often central to disease etiology and progression, so understanding GR is essential for understanding disease and developing effective therapies. While the state-of-the-art in this regard is animal and cellular models, recent advances in computational tools offer another avenue to investigate GR. A major challenge for computational models is bridging from the cellular scale (at which changes are actually occurring) to the macroscopic, geometric-scale (at which physiological consequences arise). Thus, many computational models simplify one scale or another in the name of computational tractability. In this work, we develop a discrete-continuum modeling scheme for analyzing GR, in which we apply changes directly to the discrete cell and extracellular matrix (ECM) architecture and pass those changes up to a finite-element macroscale geometry. We demonstrate the use of the model in three case-study scenarios: the media of a thick-walled artery, and the media and adventitia of a thick-walled artery, and chronic dissection of an arterial wall. We analyze each case in terms of the new and insightful data that can be gathered from this technique, and we compare our results from this model to several others. STATEMENT OF SIGNIFICANCE: This work is significant in that it provides a framework for combining discrete, microstructural- and cellular-scale models to the growth and remodeling of large tissue structures (such as the aorta). It is a significant advance in that it couples the microscopic remodeling with an existing macroscopic finite element model, making it relatively easy to use for a wide range of conceptual models. It has the potential to improve understanding of many growth and remodeling processes, such as organ formation during development and aneurysm formation, growth, and rupture.

Introduction The field of medicine is experiencing a crisis as high levels of physician and trainee burnout threaten the pipeline of future physicians. Grit, or passion and perseverance for long-term goals, has been studied in high-performing and elite military units and found to be predictive of successful completion of training in adverse conditions. The Uniformed Services University of the Health Sciences (USU) graduates military medical leaders who make up a significant portion of the Military Health System physician workforce. Taken together, an improved understanding of the relationships between burnout, well-being, grit, and retention among USU graduates is critical to the success of the Military Health System. Materials and Methods The current study was approved by the Institutional Review Board at USU and explored these relations among 519 medical students across three graduating classes. These students participated in two surveys approximately one year apart from October 2018 until November 2019. Participants completed measures on grit, burnout, and likelihood of leaving the military. These data were then merged with demographic and academic data (e.g., Medical College Admission Test scores) from the USU Long Term Career Outcome Study. These variables were then analyzed simultaneously using structural equation modeling to examine the relationships among variables in a single model. Results Results reaffirmed the 2-factor model of grit as both passion and perseverance (or interest consistency). No significant relationships emerged between burnout and other study variables. Sustained and focused interest was predictive of less likelihood of staying in the military. Conclusion This study offers important insights into the relationship among well-being factors, grit, and long-term career planning in the military. The limitations of using a single-item measure of burnout and measuring behavioral intentions in a short time frame during undergraduate medical education highlight the importance of future longitudinal studies that can examine actual behaviors across a career lifespan. However, this study offers some key insights into potential impacts on the retention of military physicians. The findings suggest that military physicians who are most likely to stay in the military tend to embrace a more fluid and flexible medical specialty path. This is critical in expectation setting for the military to train and retain military physicians across a wide range of critical wartime specialties.

Micromechanical studies of mitotic chromosomes have revealed them to be remarkably extensible objects and informed early models of mitotic chromosome organization. We use a data-driven, coarsegrained polymer modeling approach, capable of generating ensembles of chromosome structures that are quantitatively consistent with experiments, to explore the relationship between the spatial organization of individual chromosomes and their emergent mechanical properties. In particular, we investigate the mechanical properties of our model chromosomes by axially stretching them. Simulated stretching led to a linear force-extension curve for small strain, with mitotic chromosomes behaving about ten-fold stiffer than interphase chromosomes. Studying the relaxation dynamics we found that chromosomes are viscoelastic solids, with a highly liquid-like, viscous behavior in interphase that becomes solid-like in mitosis. This emergent mechanical stiffness in our model originates from lengthwise compaction, an effective potential capturing the activity of loop-extruding SMC complexes. Chromosomes denature under large strains via unraveling, which is characterized by opening of large-scale folding patterns. By quantifying the effect of mechanical perturbations on the chromosome’s structural features, our model provides a nuanced understanding of in vivo mechanics of chromosomes.

Background Well-being concerns among medical students are more prevalent than their age-matched peers in the United States. It remains unknown, however, if individual differences in well-being exist among U.S. medical students serving in the military. In this study, we sought to identify profiles (i.e., subgroups) of well-being in military medical students and examine the associations between these well-being profiles and burnout, depression, and intended retention in military and medical fields. Methods Using a cross-sectional research design, we surveyed military medical students and then conducted latent class analysis to explore profiles of well-being, and applied the three-step latent class analysis method to assess predictors and outcomes of well-being profiles. Results Heterogeneity in well-being was identified among the 336 military medical students surveyed, portraying medical students’ falling into three distinct subgroups: High well-being (36%), low well-being (20%), and moderate well-being (44%). Different subgroups were associated with different risks of outcomes. Students in the subgroup of low well-being were at the highest risk of burnout, depression, and leaving medicine. In contrast, students in the moderate well-being group were at the highest risk of leaving military service. Conclusions These subgroups may be clinically important as burnout, depression, and intention to leave medical field and/or military service occurred with varying likelihoods among medical students across the different well-being subgroups. Military medical institutions may consider improving recruitment tools to identify the best alignment between students’ career goals and the military setting. Besides, it is crucial for the institution to address diversity, equity, and inclusion issues that may lead to alienation, anxiety, and a sense of wanting to leave the military community.

The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by the Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs).From September 19, 2012, to December 31, 2021, there were 1,355 devices in 1,109 patients (19 years) from 42 North American Hospitals.Cardiomyopathy was the most common underlying etiology (58%), followed by congenital heart disease (CHD) (26%) and myocarditis (9%). Regarding device type, implantable continuous (IC) VADs were most common at 40%, followed by paracorporeal pulsatile (PP) (28%), and paracorporeal continuous (PC) (27%). Baseline demographics differed, with the PC cohort being younger, smaller, more complex (ie. CHD), and sicker at implant (P.0001). At six months post-VAD implantation, a favorable outcome (transplant, recovery, or alive on device) was achieved in 84% of patients, which was greatest among those on IC VADs (92%) and least for PC VADs (69%). Adverse events (AEs) were not uncommon, with non-gastrointestinal bleeding (incidence of 14%) and neurological dysfunction (11% [Stroke 4%]), within 2 weeks post implant being the most prevalent. Stroke and bleeding had negative impacts on overall survival (p=0.002 and p0.001, respectively).This Sixth Pedimacs Report demonstrates the continued evolution of the pediatric field. The complexity of cardiac physiologies and anatomical constraint mandates the need for multiple types of devices utilized (PC, PP, IC). Detailed analyses of each device type in this report provide valuable information to further advance the care of this challenging and vulnerable population.

Introduction Physical and psychological well-being play a critical role in the academic and professional development of medical students and can alter the trajectory of a student’s quality of personal and professional life. Military medical students, given their dual role as officer and student, experience unique stressors and issues that may play a role in their future intentions to continue military service, as well as practice medicine. As such, this study explores well-being across the 4 years of medical school at Uniformed Services University (USU) and how well-being relates to a student’s likelihood to continue serving in the military and practicing medicine. Methods In September 2019, 678 USU medical students were invited to complete a survey consisting of three sections—the Medical Student Well-being Index (MSWBI), a single-item burnout measure, and six questions regarding their likelihood of staying in the military and medical practice. Survey responses were analyzed using descriptive statistics, analysis of variance (ANOVA), and contingency table analysis. Additionally, thematic analysis was conducted on open-ended responses included as part of the likelihood questions. Results Our MSWBI and burnout scores suggest that the overall state of well-being among medical students at USU is comparable to other studies of the medical student population. ANOVA revealed class differences among the four cohorts, highlighted by improved well-being scores as students transitioned from clerkships to their fourth-year curriculum. Fewer clinical students (MS3s and MS4s), compared to pre-clerkship students, indicated a desire to stay in the military. In contrast, a higher percentage of clinical students seemed to “reconsider” their medical career choice compared to their pre-clerkship student counterparts. “Medicine-oriented” likelihood questions were associated with four unique MSWBI items, whereas “military-oriented” likelihood questions were associated with one unique MSWBI item. Conclusion The present study found that the overall state of well-being in USU medical students is satisfactory, but opportunities for improvement exist. Medical student well-being seemed to have a stronger association with medicine-oriented likelihood items than with military-oriented likelihood items. To obtain and refine best practices for strengthening engagement and commitment, future research should examine if and how military and medical contexts converge and diverge throughout training. This may enhance the medical school and training experience and, ultimately, reinforce, or strengthen, the desire and commitment to practice and serve in military medicine.

The study aims to (1) examine the spatiotemporal map of magnetoencephalography-evoked responses during an Auditory Memory Retrieval and Silent Repeating (AMRSR) task, and determine the hemispheric dominance for language, and (2) evaluate the accuracy of the AMRSR task in Wernicke and Broca area localization.In 30 patients with brain tumors and/or epilepsies, the AMRSR task was used to evoke magnetoencephalography responses. We applied Fast VEctor-based Spatial-Temporal Analyses with minimum L1-norm source imaging method to the magnetoencephalography responses for localizing the brain areas evoked by the AMRSR task.The Fast-VEctor-based Spatial-Temporal Analysis found consistent activation in the posterior superior temporal gyrus around 300 to 500 ms, and another activation in the frontal cortex (pars opercularis and/or pars triangularis) around 600 to 900 ms, which were localized to the Wernicke area (BA 22) and Broca area (BA 44 and BA 45), respectively. The language-dominant hemispheric laterization elicited by the AMRSR task was comparable with the result from an Auditory Dichotic task result given to the same patient, with the exception that AMRSR is more sensitive on bilateral language laterization cases on finding the Wernicke and Broca areas.For all patients who successfully finished the AMRSR task, Fast-VEctor-based Spatial-Temporal Analysis could establish accurate and robust localizations of Broca and Wernicke area and determine hemispheric dominance. For subjects with normal auditory functionality, the AMRSR paradigm evaluation showed significant promise in providing reliable assessments of cerebral language dominance and language network localization.

Isomeric molecules are important analytes in many biological and chemical arenas, yet their similarity poses challenges for many analytical methods, including mass spectrometry (MS). Tandem-MS provides significantly more information about isomers than intact mass analysis, but highly similar fragmentation patterns are common and include cases where no unique m/z peaks are generated between isomeric pairs. However, even in such situations, differences in peak intensity can exist and potentially contain additional information. Herein, we present a framework for comparing mass spectra that differ only in terms of peak intensity and include calculation of a statistical probability that the spectra derive from different analytes. This framework allows for confident identification of peptide isomers by collision-induced dissociation, higher-energy collisional dissociation, electron-transfer dissociation, and radical-directed dissociation. The method successfully identified many types of isomers including various d/l amino acid substitutions, Leu/Ile, and Asp/IsoAsp. The method can accommodate a wide range of changes in instrumental settings including source voltages, isolation widths, and resolution without influencing the analysis. It is shown that quantification of the composition of isomeric mixtures can be enabled with calibration curves, which were found to be highly linear and reproducible. The analysis can be implemented with data collected by either direct infusion or liquid-chromatography MS. Although this framework is presented in the context of isomer characterization, it should also prove useful in many other contexts where similar mass spectra are generated.

Radical-directed dissociation (RDD) is a fragmentation technique in which a radical created by selective 213/266 nm photodissociation of a carbon-iodine bond is reisolated and collisionally activated. In previous RDD experiments, collisional activation was effected by ion-trap collision-induced dissociation (CID). Higher-energy collisional dissociation (HCD) differs from CID both in terms of how ions are excited and in the number, type, or abundance of fragments that are observed. In this paper, we explore the use of HCD for activation in RDD experiments. While RDD-CID favors fragments produced from radical-directed pathways such as a/z-ions and side chain losses regardless of the activation energy employed, RDD-HCD spectra vary considerably as a function of activation energy, with lower energies favoring RDD while higher energies favor products resulting from cleavage directed by mobile protons (b/y-ions). RDD-HCD therefore affords more tunable fragmentation based on the HCD energy provided. Importantly, the abundance of radical products decreases as a function of increasing HCD energy, confirming that RDD generally proceeds via lower-energy barriers relative to mobile-proton-driven dissociation. The dominance of b/y-ions at higher energies for RDD-HCD can therefore be explained by the higher survivability of fragments not containing the radical after the initial or subsequent dissociation events. Furthermore, these results confirm previous suspicions that HCD spectra differ from CID spectra due to multiple dissociation events.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the United Kingdom). Data on invasive EOC diagnosed in women aged 15-99 years during 1995-2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group, and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995-2014 among women aged 65-99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma 'not otherwise specified' with estimates ranging between 4.4% and 7.4% in women aged 15-64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival. This article is protected by copyright. All rights reserved.

The world's eastern boundary upwelling systems (EBUSs) contribute disproportionately to global ocean productivity and provide critical ecosystem services to human society. The impact of climate change on EBUSs and the ecosystems they support is thus a subject of considerable interest. Here, we review hypotheses of climate-driven change in the physics, biogeochemistry, and ecology of EBUSs; describe observed changes over recent decades; and present projected changes over the twenty-first century. Similarities in historical and projected change among EBUSs include a trend toward upwelling intensification in poleward regions, mitigated warming in near-coastal regions where upwelling intensifies, and enhanced water-column stratification and a shoaling mixed layer. However, there remains significant uncertainty in how EBUSs will evolve with climate change, particularly in how the sometimes competing changes in upwelling intensity, source-water chemistry, and stratification will affect productivity and ecosystem structure. We summarize the commonalities and differences in historical and projected change in EBUSs and conclude with an assessment of key remaining uncertainties and questions. Future studies will need to address these questions to better understand, project, and adapt to climate-driven changes in EBUSs. Expected final online publication date for the

Polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (PCDD/F) are persistent, toxic, and bioaccumulative. Currently, PCDD/F monitoring programs primarily use fish and birds with potentially large home ranges to monitor temporal trends over broad spatial scales; sentinel organisms that provide targeted sediment contaminant information across small geographic areas have yet to be developed. Riparian orb-weaving spiders, which typically have small home ranges and consume primarily adult aquatic insects, are potential PCDD/F sentinels. Recent studies have demonstrated that spider tissue concentrations indicate the source and magnitude of dioxin-like chlorinated compounds in contaminated sediments, including polychlorinated biphenyls (PCBs). Our aim in the present study was to assess the utility of riparian spiders as sentinels for PCDD/F-contaminated sediments. We measured PCDD/F (total [Σ] and homologs) in surface sediments and spiders collected from three sites within the St. Louis River basin (Minnesota and Wisconsin, USA). We then compared (1) patterns in ΣPCDD/F concentrations between sediment and spiders, (2) the distribution of homologs within sediments and spiders when pooled across sites, and (3) the relationship between sediment and spider concentrations of PCDD/F homologs across 13 stations sampled across the three sites. The ΣPCDD/F concentrations in sediment (mean ± standard error 286 591 ± 97 614 pg/g) were significantly higher than those in riparian spiders (2463 ± 977 pg/g, p < 0.001), but the relative abundance of homologs in sediment and spiders were not significantly different. Spider homolog concentrations were significantly and positively correlated with sediment concentrations across a gradient of sediment PCDD/F contamination (R(2) = 0.47, p < 0.001). Our results indicate that, as has been shown for other legacy organic chemicals like PCBs, riparian spiders are suitable sentinels of PCDD/F in contaminated sediment.

In order to gain a better understanding of post-stroke dietary behaviors (e.g., selecting, accessing, and preparing healthy foods) among chronic, community-dwelling stroke survivors, we conducted a mixed-methods study consisting of a quantitative online survey (n = 63) and follow-up focus groups with a subset of participants (n = 7). Perceived performance, assistance required, adaptive equipment and compensatory strategies used, and sources of education and training were examined. Results demonstrated (1) diminished post-stroke performance for most dietary behaviors (e.g., grocery shopping, meal preparation), (2) an increased desire to eat healthily to prevent recurrent stroke, (3) variable use of adaptive equipment and compensatory strategies, and (4) limited healthcare-based dietary behavior education and training. These results suggest that stroke survivors could benefit from increased dietary behavior intervention to improve dietary behavior performance. Findings can be used to guide clinical intervention and design future research studies.

The recent clinical success of multiple mRNA-based SARS-CoV-2 vaccines has proven the potential of RNA formulated in lipid nanoparticles (LNPs) in humans, and products based on base-modified RNA, sequence-optimized RNA, and self-replicating RNAs formulated in LNPs are all in various stages of clinical development. However, much remains to be learned about critical parameters governing the manufacturing and use of LNP-RNA formulations. One important issue that has received limited attention in the literature to date is the identification of optimal storage conditions for LNP-RNA that preserve long-term activity of the formulations. Here, we analyzed the physical structure, in vivo expression characteristics, and functional activity of alphavirus-derived self-replicating RNA (repRNA)-loaded LNPs encoding HIV vaccine antigens following storage in varying temperatures, buffers, and in the presence or absence of cryoprotectants. We found that for lipid nanoparticles with compositions similar to clinically-used LNPs, storage in RNAse-free PBS containing 10% (w/v) sucrose at -20 °C was able to maintain vaccine stability and in vivo potency at a level equivalent to freshly prepared vaccines following 30 days of storage. LNPs loaded with repRNA could also be lyophilized with retention of bioactivity.

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d. In rats and pigs with induced acute myocardial infarction followed by intracoronary infusion of the biomaterial, we observed substantially reduced left ventricular volumes and improved wall-motion scores, as well as differential expression of genes associated with tissue repair and inflammation. Delivering pro-healing extracellular matrix by intravascular infusion post injury may provide translational advantages for the healing of inflamed tissues 'from the inside out'.

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage1–3. The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes4–7. Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas8 (SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus9 (HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53 loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage.

The simple, accurate, and rapid detection of foodborne pathogens is essential for public health. Development of an immunomagnetic separation (IMS) multiplex touchdown PCR (IMS–multiplex TD–PCR) assay for simultaneous detection and distinguishing of C. jejuni and C. coli is reported herein. Polyclonal antibody (pAb) against multiepitope antigen (MEA) was conjugated to ferromagnetic nanoparticles (FMNs) to produce anti-MEA FMNs. Optimal anti-MEA FMNs loading yielded 26.7 μg of immunoglobulin G (IgG) molecules per mg of FMNs with an average size of 72 ± 9 nm, corresponding to an 83% rate of pAb conjugation. Anti-MEA FMNs (20 μg) for IMS captured culturable C. jejuni cells at 3.54 × 10 2 colony-forming unit (CFU)/mL in pure culture, while higher amounts (40 and 60 μg) reduced the recovery. The scanning electron microscope (SEM) analysis revealed the attachment of anti-MEA FMNs to target bacteria, forming aggregated cells and magnetic nanoparticles in ellipse-like shapes. The subsequent multiplex TD–PCR assay simultaneously detected and distinguished C. jejuni and C. coli at 104 CFU/mL in mixed culture and at 103 CFU/mL for each individual species. Furthermore, the limit of detection (LOD) of the IMS–multiplex TD–PCR assay was 104 CFU/g in spiked chicken breast samples. Specificity was 100% for both C. jejuni and C. coli as none of the amplicons were detected in control samples where Campylobacter was absent. This assay is able to detect and distinguish C. jejuni and C. coli simultaneously and is simple, accurate, and rapid with a time to result of 4 h without an enrichment step, making it a promising approach for rapid and culture-free detection of Campylobacter in chicken products.

Purpose This study aimed to explore the differences in muscle activity, handwriting legibility, and consistency when using the 4 primary handwriting grip styles: dynamic quadrupod (DQ), dynamic tripod, lateral quadrupod (LQ) and lateral tripod. Study Design and Methods Thirty-four 18-22-year-old participants completed a handwriting legibility test on paper as well as consistency and metrics tests using both surface electromyography and a digital writing tablet. Electromyography was used to measure the activity of 6 muscles associated with handwriting, and the tablet measured stroke duration, length, velocity, and pen pressure. Subjects used each grip style with all protocols and scores were normalized to their native grip. Significance was set at P Results Females had a lower range in legibility scores than males by 3.5% ± 1.7% (p = .046, d = 0.713), but grip style did not impact legibility. The upper trapezius (UT) was more active in the lateral tripod and LQ grips compared to DQ by 16.8% ± 5.2% and by 13.8% ± 5.2%, (p = .007, p = .012, respectively, partial η2 = 0.188). The stroke duration was greater in the LQ grip style than dynamic tripod and DQ grip styles (p = .008, p = .023, respectively; partial η2 = 0.123). Conclusions Lateral grip styles involve more whole-arm, stabilizing movements while dynamic grip styles require fine dexterous movements. Furthermore, females are likely to be able to employ any grip with minimal effect on legibility. For a patient needing guidance in rehabilitation, understanding the differences in grips could aid selection of the optimum grip style to employ based on their muscular control deficits.

To investigate the incidence of anteroinferior glenoid rim fractures (AGRFs) after anterior shoulder instability (ASI) in patients aged 50 years or older, identify risk factors for surgical intervention for AGRFs, compare initial treatment strategies, and compare clinical outcomes of patients with and without associated AGRFs.An established geographic medical record system was used to identify patients aged 50 years or older with ASI between 1994 and 2016. Patients with radiographic evidence of AGRFs were identified and matched 1:1 to patients without AGRFs. Outcome measures included recurrent instability, recurrent pain events, conversion to arthroplasty, and osteoarthritis graded with the Samilson-Prieto classification for post-instability arthritis.Overall, 177 patients were identified, with a mean follow-up period of 10.8 years. Of these patients, 41 (23.2%) had AGRFs and were matched to 41 control patients without AGRFs. The average age was 58.6 and 58.2 years for the AGRF and control groups, respectively. Rates of surgical intervention (27% vs 49%), recurrent instability (12% vs 20%), progression of osteoarthritis (34% vs 39%), and conversion to arthroplasty (2% vs 5%) were similar between AGRF patients and controls. For patients with AGRFs, increased bone fragment size (odds ratio, 1.1) and increased body mass index (odds ratio, 1.2) correlated with an increased risk of surgery. The cutoff value for an increased risk of surgery in patients with AGRFs was a fragment size 33% of the glenoid width or greater.Of patients aged 50 years or older at presentation of ASI, 23.2% presented with an associated AGRF. A fragment size 33% of the glenoid width or greater and a higher patient body mass index were significant factors for surgical intervention; however, most patients did not require surgery and still showed acceptable clinical outcomes, and the most common reason for surgical intervention was a rotator cuff tear. Overall, the presence of an AGRF did not portend a worse prognosis as treatment strategies and long-term outcomes including recurrent instability, progression of osteoarthritis, and conversion to arthroplasty were similar to those in patients without AGRFs.Level III, retrospective comparative study.

Excess in growth hormone (GH) levels, seen in patients with acromegaly, is associated with increases in fractures. This happens despite wider bones and independent of bone mineral density. We used the bovine GH (bGH) transgenic mice, which show constitutive excess in GH and insulin-like growth factor 1 (IGF-1) in serum and tissues, to study how lifelong increases in GH and IGF-1 affect skeletal integrity. Additionally, we crossed the acid labile subunit (ALS) null (ALSKO) to the bGH mice to reduce serum IGF-1 levels. Our findings indicate sexually dimorphic effects of GH on cortical and trabecular bone. Male bGH mice showed enlarged cortical diameters, but with marrow cavity expansion and thin cortices as well as increased vascular porosity that were associated with reductions in diaphyseal strength and stiffness. In contrast, female bGH mice presented with significantly smaller-diameter diaphysis, with greater cortical bone thickness and with a slightly reduced tissue elastic modulus (by microindentation), ultimately resulting in overall stronger, stiffer bones. We found increases in C-terminal telopeptide of type 1 collagen and procollagen type 1 N propeptide in serum, independent of circulating IGF-1 levels, indicating increased bone remodeling with excess GH. Sexual dimorphism in response to excess GH was also observed in the trabecular bone compartment, particularly at the femur distal metaphysis. Female bGH mice preserved their trabecular architecture during aging, whereas trabecular bone volume in male bGH mice significantly reduced and was associated with thinning of the trabeculae. We conclude that pathological excess in GH results in sexually dimorphic changes in bone architecture and gains in bone mass that affect whole-bone mechanical properties, as well as sex-specific differences in bone material properties. © 2022 American Society for Bone and Mineral Research (ASBMR).

The invasive azalea lace bug, Stephanitis pyrioides (Scott), is one of the most damaging insect pests of the genus Rhododendron, especially azaleas. Feeding by nymphs and adults reduces the aesthetic value of infested plants. Rhododendron spp. (L.) and cultivars are a major component of public and private landscapes in the Pacific Northwest, as well as other parts of the U.S.. Variability in the susceptibility of Rhododendron to S. pyrioides has been previously examined but generally on a limited number of Rhododendron species and cultivars. We measured the susceptibility of 71 Rhododendron species, varieties, and cultivars over two years, selecting plants across the phylogenetic tree of Rhododendron, and quantified the proportion of leaf damage caused by S. pyrioides. We observed that trichome presence did not predict S. pyrioides damage. Plants from the subgenus Azaleastrum were the significantly most susceptible subgenus, and all sampled plants from this subgenus had measurable damage. In contrast, plants from the subgenus Hymenanthes were the significantly least susceptible, and most Hymenanthes plants had no measurable damage. This study provides a guideline for using host plant resistance to S. pyrioides in plant selection, and emphasizes the potential for S. pyrioides management if susceptible azaleas are to be used in the landscape. Species used in this study: Azalea lace bug, Stephanitis pyrioides, Rhododendron spp.

Direct oral anticoagulants (DOACs) have been increasingly used as anticoagulation therapy in the postoperative period. However, their effectiveness in post-cardiac surgical atrial fibrillation is yet to be determined.We conducted a meta-analysis, searching three international databases from 1 January 2003 to 26 January 2022 for studies reporting on DOACs in at least 10 adult patients (18 yr of age) with post-cardiac surgical atrial fibrillation. The primary outcomes were major neurological events and bleeding; secondary outcomes were mortality, hospital and ICU length of stay, cost, and other complications from therapy. We included studies of any design, including RCTs, cohort studies with and without propensity score matching methods, and single-armed case series.Twelve studies (8587 DOACs; 8315 warfarin) were included in this meta-analysis. The incidences of postoperative bleeding and major neurological events with DOACs were 7.3% (95% confidence interval [CI]: 3.4-14.7%) and 2.2% (95% CI: 0.9-4.9%), respectively. The incidence of major neurological events was lower in high-risk patients, including those with hypertension and higher CHADOACs reduced bleeding and major neurological events in patients with post-cardiac surgical atrial fibrillation, appearing safer than warfarin in this context. However, which specific DOAC provides the most effective anticoagulation in this patient population needs further investigation.PROSPERO CRD42021282777.

Summary Chemical enhanced oil recovery (EOR) flooding is one of the more attractive methods to improve oil recovery. However, during times of instability in the oil market, cost of specialized chemicals and necessary facilities for alkali-surfactant-polymer (ASP) or surfactant-polymer makes this technology very expensive and challenging to implement in the field. In the majority of cases, polymer flooding alone has proved to be the most cost-effective solution that has resulted in attractive and predictable return on investment. In recent times, a challenging economic environment has operators looking for added economic and sustainable savings. The possibility of reinjection of produced (sheared) polymer to offset injection concentration requirements can lead to reduced cost and longer sustainability of oil recovery, thus offering a subsequent reduction in produced water (PW) treatment and a reduced full-cycle carbon footprint. This innovative approach is subject to conditions experienced in the surface facilities, as well as in the reservoir. As part of this study, different polymer chemistries were investigated for their mobility control in porous media and comparative effect on oil recovery trends in the presence of produced fluid containing residual polymer. The initial fluid-fluid testing and laboratory characterization results were validated against a mature field EOR project for reduction in polymer requirement to achieve target viscosity. Monophasic flow behavior experiments were performed in Bentheimer and Berea outcrop cores, while oil recovery experiments were performed in Bentheimer outcrops with different polymer solutions—freshly made and combinations with residual produced polymer. Based on field observations and laboratory measurements, a 10 to 15% reduction in fresh polymer loading could be achieved through the reutilization of water containing residual polymer in these specific field conditions. Note, this case study involved produced polymer that was degraded through progressive cavity pumps (PCPs) resulting in only 15 to 20% of the injected viscosity in the produced fluids in addition to thermal and chemical degradations. The monophasic injectivity experiments in both outcrop cores resulted in similar resistance factors (RFs) for fresh polymer and blends with produced water reinjection containing residual polymer (PWcRP) solution, establishing the robustness of this blending system. Oil recovery experiments also resulted in similar oil displacement behavior [approximately 30 to 40% oil originally in place (OOIP) after 0.5 pore volumes (PV) waterflood] for fresh and blends with sheared polymer solutions, validating no loss in recovery potential, with the added benefit of 10 to 15% polymer loading reduction.

Management of critically ill patients requires simultaneous administration of many medications. Treatment for patient comorbidities may lead to drug–drug interactions which decrease drug efficacy or increase adverse reactions. Current practices rely on a one-size-fits-all dosing approach. Pharmacogenetic testing is generally reserved for addressing problems rather than used proactively to optimize care. We hypothesized that burn and surgery patients will have one or more genetic variants in drug metabolizing pathways used by one or more medications administered during the patient’s hospitalization. The aim of this study was to determine the frequency of variants with abnormal function in the primary drug pathways and identify which medications may be impacted. Genetic (19 whole exome and 11 whole genome) and medication data from 30 pediatric burn and surgery patients were analyzed to identify pharmacogene–drug associations. Nineteen patients were identified with predicted altered function in one or more of the following genes: CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The majority had decreased function, except for several patients with CYP2C19 rapid or ultrarapid variants. Some drugs administered during hospitalization that rely on these pathways include hydrocodone, oxycodone, methadone, ibuprofen, ketorolac, celecoxib, diazepam, famotidine, diphenhydramine, and glycopyrrolate. Approximately one-third of the patients tested had functionally impactful genotypes in each of the primary drug metabolizing pathways. This study suggests that genetic variants may in part explain the vast variability in drug efficacy and suggests that future pharmacogenetics research may optimize dosing regimens.

Purpose The fused filament fabrication (FFF) process is an additive manufacturing technique used in engineering design. The mechanical properties of parts manufactured by FFF are influenced by the printing parameters. The mechanical properties of rigid thermoplastics for FFF are well defined, while thermoplastic elastomers (TPE) are uncommonly investigated. The purpose of this paper is to investigate the influence of extruder temperature, bed temperature and printing speed on the mechanical properties of a thermoplastic elastomer. Design/methodology/approach Regression models predicting mechanical properties as a function of extruder temperature, bed temperature and printing speed were developed. Tensile specimens were tested according to ASTM D638. A 3×3 full factorial analysis, consisting of 81 experiments and 27 printing conditions was performed, and models were developed in Minitab. Tensile tests verifying the models were conducted at two selected printing conditions to assess predictive capability. Findings Each mechanical property was significantly affected by at least two of the investigated FFF parameters, where printing speed and extruder temperature terms influenced all mechanical properties (p < 0.05). Notably, tensile modulus could be increased by 21%, from 200 to 244 MPa. Verification prints exhibited properties within 10% of the predictions. Not all properties could be maximized together, emphasizing the importance of understanding FFF parameter effects on mechanical properties when making design decisions. Originality/value This work developed a model to assess FFF parameter influence on mechanical properties of a previously unstudied thermoplastic elastomer and made property predictions within 10% accuracy.

Background Women who use drugs (WWUD) have low rates of contraceptive use and high rates of unintended pregnancy. Drug use is common among women in rural U.S. communities, with limited data on how they utilize reproductive, substance use disorder (SUD), and healthcare services. Objective We determined contraceptive use prevalence among WWUD in rural communities then compared estimates to women from similar rural areas. We investigated characteristics of those using contraceptives, and associations between contraceptive use and SUD treatment, healthcare utilization, and substance use. Design Rural Opioids Initiative (ROI) — cross-sectional survey using respondent-driven sampling (RDS) involving eight rural U.S. regions (January 2018–March 2020); National Survey on Family Growth (NSFG) — nationally-representative U.S. household reproductive health survey (2017–2019). Participants Women aged 18–49 with prior 30-day non-prescribed opioid and/or non-opioid injection drug use; fecundity determined by self-reported survey responses. Main Measures Unweighted and RDS-weighted prevalence estimates of medical/procedural contraceptive use; chi-squared tests and multi-level linear regressions to test associations. Key Results Of 855 women in the ROI, 36.8% (95% CI 33.7–40.1, unweighted) and 38.6% (95% CI 30.7–47.2, weighted) reported contraceptive use, compared to 66% of rural women in the NSFG sample. Among the ROI women, 27% had received prior 30-day SUD treatment via outpatient counseling or inpatient program and these women had increased odds of contraceptive use (aOR 1.50 [95% CI 1.08–2.06]). There was a positive association between contraception use and recent medications for opioid use disorder (aOR 1.34 [95% CI 0.95–1.88]) and prior 6-month primary care utilization (aOR 1.32 [95% CI 0.96–1.82]) that did not meet the threshold for statistical significance. Conclusion WWUD in rural areas reported low contraceptive use; those who recently received SUD treatment had greater odds of contraceptive use. Improvements are needed in expanding reproductive and preventive health within SUD treatment and primary care services in rural communities.

Digital adherence technologies like 99DOTS are increasingly considered as an alternative to directly observed therapy for tuberculosis (TB) treatment supervision. We evaluated the cost and cost-effectiveness of 99DOTS in a high-TB-burden setting.We assessed the costs of implementing 99DOTS in Uganda through a pragmatic, stepped-wedge randomized trial. We measured costs from the health system perspective at 5 of 18 study facilities. Self-reported service activity time data were used to assess activity-based service costs; other costs were captured from budgets and key informant discussions using standardized forms. We estimated costs and effectiveness considering the 8-month study period ("trial specific") and using a 5-year time horizon ("extended activities"), the latter including a "marginal clinic" expansion scenario that ignored above-site implementation costs. Cost-effectiveness was assessed as cost per patient successfully completing treatment, using Monte Carlo simulation, cost-effectiveness acceptability curves, and sensitivity analyses to evaluate uncertainty and robustness of results.The total cost of implementing 99DOTS in the "trial-specific" scenario was $99 554 across 18 clinics (range $3771-$6238 per clinic). The cost per treatment success in the "trial-specific" scenario was $355 (range $229-$394), falling to $59 (range $50-$70) assuming "extended activities," and $49 (range $42-$57) in the "marginal clinic" scenario. The incremental cost-effectiveness of 99DOTS in the "extended-activity" scenario was $355 per incremental treatment success.Costs and cost-effectiveness of 99DOTS were influenced by the degree to which infrastructure is scaled over time. If sustained and scaled up, 99DOTS can be a cost-effective option for TB treatment adherence support in high-TB-burden settings like Uganda.

Wear and corrosion at the junctions of modular implants are increasingly recognized issues in the design of hip and knee arthroplasty prostheses, yet less is known about their significance in shoulder arthroplasty.A query of paired total shoulder implant specimens (eg, humeral head and stem components from the same patient) was performed using an institutional implant retrieval registry. Implants were examined under a stereomicroscope and evaluated for evidence of fretting and corrosion using the modified Goldberg scoring system. Available electronic medical records of included specimens were reviewed to report relevant clinical characteristics and identify potential associations with the presence of tribocorrosion.Eighty-three paired total shoulder implant specimens, explanted at a single institution between 2013 and 2020, were analyzed. Corrosion was identified in 52% (43/83) of humeral head components and 40% (33/83) of humeral stem components. Fretting was identified in 29% (24/83) of humeral head components and 28% (23/83) of humeral stem components. Of the 56 paired implants for which clinical data were available, the duration of implantation (DOI) was less than 2 years in 29% of paired implants and greater than 5 years in 36% of implants. The presence of corrosion or fretting was not associated with DOI, a male humeral head taper, or periprosthetic infection as the indication for revision.Mild tribocorrosion was present in more than half of the retrieved humeral implant specimens. However, trunnionosis did not manifest as a clinical cause of revision surgery in our study.

Background and aimsLipoprotein(a) [Lp(a)] is causally associated with aortic valve stenosis (AS) but Lp(a) testing among AS patients is not broadly incorporated into clinical practice. We evaluated trends in Lp(a) testing in an academic medical center.MethodsEducational efforts and adding Lp(a) to the lipid panel on the electronic medical record (EMR) and pre-procedure order sets were used to increase awareness of Lp(a) as a risk factor in AS. Medical records at University of California San Diego Health (UCSDH) were analyzed from 2010 to 2020 to define the yearly frequency of first time Lp(a) testing in patients with diagnosis codes for AS or undergoing transcatheter aortic valve replacement (TAVR).ResultsLp(a) testing for any indication increased over 5-fold from 2010 to 2020. A total of 3808 patients had a diagnosis of AS and 417 patients had TAVR. Lp(a) levels >30mg/dL were present in 37% of AS and 35% of TAVR patients. The rates of Lp(a) testing in AS and TAVR were 14.0% and 65.7%, respectively. In AS, Lp(a) testing increased over time from 8.5% in 2010, peaking at 24.2% in 2017, and declining to 13.9% in 2020 (p&nbsp