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Purpose: To understand therapeutic priorities, a secondary data analysis on a retrospective cohort was conducted to classify rehabilitation goals according to the International Classification of Functioning, Disability, and Health (ICF). Materials and Methods: Therapeutic goals from an initial outpatient physical or occupational therapy evaluation for patients post-stroke or with Parkinson disease, were classified into Level 1 of the ICF. Goals in the Activity and Participation component were further sub-classified as activity capacity or activity performance (self-report or direct) in daily life. Results: 776 goals across 104 participants were classified into Level 1 of the ICF. The majority, 73% (563/776) were classified as Activity and Participation, 20% (155/776) as Body Function and 2% (17/776) as Environmental Factors. Fifty-two percent (400/776) of all goals were classified as activity capacity and 21% (163/776) as activity performance in daily life, with 21% (160/776) of goals measuring self-report activity performance in daily life and less than 1% (3/776) of goals measuring direct activity performance in daily life. Conclusions: While the majority of therapeutic goals were classified into the Activity and Participation component, less than 1% of goals measured direct activity performance in daily life. If people seek outpatient rehabilitation to improve functioning in their real-world environment, therapeutic goal setting should reflect this. PREVIOUS PRESENTATION WORK: Portions of this content were presented at the 2023 Academy of Neurologic Physical Therapy Annual Conference and will be presented at the 2023 TIRR & UT Health International Stroke Rehab & Recovery Conference. IMPLICATIONS FOR REHABILITATION: The majority of therapeutic goals for an episode of outpatient neurorehabilitation were classified into the Activity and Participation component of the International Classification of Functioning, Disability, and Health. However, less than 1% of therapeutic goals measured direct activity performance in daily life. If people with neurological diagnoses seek out outpatient rehabilitation to improve functioning in their real-world environment, than therapeutic goal setting should reflect this. [ABSTRACT FROM AUTHOR]

Background Vaccines and vaccine boosting have blunted excess morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in older nursing home residents (NHR). However, the impact of repeated vaccination on the T-cell response based on biological sex and prior infection of NHR remain understudied. Methods We examined T-cell responses to SARS-CoV-2 mRNA vaccines in a cohort of NHR and healthcare workers (HCW) over 2 years. We used interferon-γ ELIspot and flow cytometry to assess T-cell response before, 2 weeks, and 6 months after the initial series and each of 2 booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T-cell effector function. Results Prior SARS-CoV-2 infection and female sex contributed to higher T-cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T-cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations. Conclusions These results suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T-cell response to mRNA vaccination. [ABSTRACT FROM AUTHOR]

Eighteen lightning flash rate parameterization schemes (FRPSs) were investigated in a Weather Research and Forecasting model coupled with chemistry cloud‐resolved simulation of the 29–30 May 2012 supercell storm system observed during the Deep Convective Clouds and Chemistry (DC3) field campaign. Most of the observed storm's meteorological conditions were well represented when the model simulation included both convective damping and lightning data assimilation techniques. Newly‐developed FRPSs based on DC3 radar observations and Lightning Mapping Array data are implemented in the model, along with previously developed schemes from the literature. The schemes are based on relationships between lightning and various kinematic, structural, and microphysical thunderstorm characteristics (e.g., cloud top height, hydrometeors, reflectivity, and vertical velocity) available in the model. The results suggest the model‐simulated graupel and snow/ice hydrometeors require scaling factors to more closely represent proxy observations. The model‐simulated lightning flash trends and total flashes generated by each scheme over the simulation period are compared with observations from the central Oklahoma Lightning Mapping Array. For this supercell system, 13 of the 18 schemes overpredicted flashes by >100% with the group of FRPSs based on storm kinematics and structure (particularly updraft volume) performing slightly better than the hydrometeor‐based schemes. During the storm's first 4 hr, the upward cloud ice flux FRPS, which is based on the combination of vertical velocity and hydrometeors, well represents the observed total flashes and flash rate trend; while, the updraft volume scheme well represents the observed flash rate peak and subsequent sharp decline in flash rate. Plain Language Summary: Accurate lightning forecasts are important for daily activities. They are also important because lightning produces nitrogen oxide, which affects the distribution of atmospheric trace gases that have significant roles in influencing our climate (e.g., ozone). Lightning is recreated in weather models using already determined relationships between observed lightning and thunderstorm characteristics (e.g., hydrometeors and vertical velocity). Lightning prediction is also highly dependent on how well the model represents current conditions, like thunderstorm location and strength. Eighteen lightning‐thunderstorm relationships, or schemes, were investigated in a cloud‐resolved Weather Research and Forecasting model coupled with chemistry to simulate the 29–30 May 2012 supercell storm system observed during the Deep Convective Clouds and Chemistry (DC3) field campaign and to identify the best scheme associated with the event. Modifications to the model‐simulation were first required to better represent the observed convection before comparing the observed and model‐simulated lightning. Generally, the schemes based on storm kinematics and structure perform slightly better for this case study than the microphysical schemes. Two schemes (i.e., upward cloud ice flux and updraft volume) well represent the supercell system's lightning activity. The upward cloud ice flux scheme was used in follow‐on lightning chemistry and trace gas analyses. Key Points: Thirteen of eighteen flash rate parameterization schemes overestimated the observed number of flashes by more than 100%Upward cloud ice flux and updraft volume schemes well represent lightning activity in the early and later stages of the storm, respectivelyFlash rate prediction is highly dependent on how schemes are applied in cloud‐resolved models and on accurate simulation of storm variables [ABSTRACT FROM AUTHOR]

The article discusses the rise of unionization in newsrooms, particularly in digital newsrooms, as journalists seek better working conditions. The author highlights the power imbalances between newsroom workers and corporate owners, who prioritize profit over labor rights. Unions play a crucial role in advocating for better wages, benefits, and workplace protections for all workers, regardless of union membership. The article also emphasizes the importance of unions in fostering a sense of community and empowerment among journalists. Additionally, the article addresses issues of burnout, lack of diversity, and the need for improved representation in newsrooms. [Extracted from the article]

(1) Vitamin D deficiency is associated with mortality in the general population and has been observed in one rheumatoid arthritis (RA) cohort. Here, we investigate the relationship between 25-hydroxyvitamin D (25(OH)D) levels before methotrexate (MTX) therapy initiation in patients with RA and the subsequent all-cause mortality in a national Veterans Affairs (VA) cohort. (2) This is a retrospective study on RA patients time-oriented around the initial MTX prescription and 25(OH)D levels before starting MTX. We examined survival in patients with 25(OH)D levels > 50 nmol/L and ≤50 nmol/L using the Cox Proportional Hazard Model and fully adjusted for risk factors. (3) In total, 15,109 RA patients were included in the nationwide cohort. RA patients with 25(OH)D levels > 50 nmol/L before starting MTX had a 28% reduced risk of mortality when compared to those with levels ≤ 50 nmol/L (HR: 0.72, CI: 0.64–0.80, p < 0.001) after adjusting for traditional risk factors. (4) In this national RA cohort receiving standard-of-care MTX, patients with 25(OH)D levels > 50 nmol/L have a lower subsequent mortality when compared to those with 25(OH)D levels ≤ 50 nmol/L. It remains to be determined whether increasing Vitamin D levels in RA patients initially found to be Vitamin D deficient impacts their all-cause mortality. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) that presents with varied clinical manifestations ranging from asymptomatic or mild infections and pneumonia to severe cases associated with cytokine storm, acute respiratory distress syndrome (ARDS), and even death. The underlying mechanisms contributing to these differences are unclear, although exacerbated inflammatory sequelae resulting from infection have been implicated. While advanced aging is a known risk factor, the precise immune parameters that determine the outcome of SARS-CoV-2 infection in elderly individuals are not understood. Here, we found aging-associated (age =61) intrinsic changes in T cell responses when compared to those from individuals aged = 60, even among COVIDpositive patients with mild symptoms. Specifically, when stimulated with SARSCoV-2 peptides in vitro, peripheral blood mononuclear cell (PBMC) CD4+ and CD8+ T cells from individuals aged =61 showed a diminished capacity to produce IFN-g and IL-1b. Although they did not have severe disease, aged individuals also showed a higher frequency of PD-1+ cells and significantly diminished IFN-g/PD-1 ratios among T lymphocytes upon SARS-CoV-2 peptide stimulation. Impaired T cell IL-1b expression coincided with reduced NLRP3 levels in T lymphocytes. However, the expression of these molecules was not affected in the monocytes of individuals aged =61. Together, these data reveal SARS-CoV-2-specific CD4+ and CD8+ T-cell intrinsic cytokine alterations in the individuals older than 61 and may provide new insights into dysregulated COVID-directed immune responses in the elderly. [ABSTRACT FROM AUTHOR]

Both acute and chronic hepatitis C virus (HCV) infections are characterized by inflammation. HCV and reduced liver blood filtration contribute to inflammation; however, the mechanisms of systemic immune activation and dysfunction as a result of HCV infection are not clear. We measured circulating inflammatory mediators (IL-6, IP10, sCD163, sCD14), indices of endotoxemia (EndoCab, LBP, FABP), and T cell markers of exhaustion and senescence (PD-1, TIGIT, CD57, KLRG-1) in HCV-infected participants, and followed a small cohort after direct-acting anti-viral therapy. IL-6, IP10, Endocab, LBP, and FABP were elevated in HCV participants, as were T cell co-expression of exhaustion and senescence markers. We found positive associations between IL-6, IP10, EndoCab, LBP, and co-expression of T cell markers of exhaustion and senescence. We also found numerous associations between reduced liver function, as measured by plasma albumin levels, and T cell exhaustion/senescence, inflammation, and endotoxemia. We found positive associations between liver stiffness (TE score) and plasma levels of IL-6, IP10, and LBP. Lastly, plasma IP10 and the proportion of CD8 T cells co-expressing PD-1 and CD57 decreased after initiation of direct-acting anti-viral therapy. Although associations do not prove causality, our results support the model that translocation of microbial products, resulting from decreased liver blood filtration, during HCV infection drives chronic inflammation that results in T cell exhaustion/senescence and contributes to systemic immune dysfunction. [ABSTRACT FROM AUTHOR]

Background People with human immunodeficiency virus (PWH) are at increased risk for comorbidities, and plasma interleukin 6 (IL-6) levels are among the most robust predictors of these outcomes. Tocilizumab (TCZ) blocks the receptor for IL-6, inhibiting functions of this cytokine. Methods This was a 40-week, placebo-controlled, crossover trial (NCT02049437) where PWH on stable antiretroviral therapy (ART) were randomized to receive 3 monthly doses of TCZ or matching placebo intravenously. Following a 10-week treatment period and a 12-week washout, participants were switched to the opposite treatment. The primary endpoints were safety and posttreatment levels of C-reactive protein (CRP) and CD4+ T-cell cycling. Secondary endpoints included changes in inflammatory indices and lipid levels. Results There were 9 treatment-related toxicities of grade 2 or greater during TCZ administration (mostly neutropenia) and 2 during placebo administration. Thirty-one of 34 participants completed the study and were included in a modified intent-to-treat analysis. TCZ reduced levels of CRP (median decrease, 1819.9 ng/mL, P <.0001; effect size, 0.87) and reduced inflammatory markers in PWH, including D-dimer, soluble CD14, and tumor necrosis factor receptors. T-cell cycling tended to decrease in all maturation subsets after TCZ administration, but was only significant among naive CD4 T cells. Lipid levels, including lipid classes that have been related to cardiovascular disease risk, increased during TCZ treatment. Conclusions TCZ is safe and decreases inflammation in PWH; IL-6 is a key driver of the inflammatory environment that predicts morbidity and mortality in ART-treated PWH. The clinical significance of lipid elevations during TCZ treatment requires further study. Clinical Trials Registration. NCT02049437. [ABSTRACT FROM AUTHOR]

Thin‐film photovoltaic device efficiencies are limited by carrier recombination, thus understanding recombination mechanisms is critical for performance improvements. Bulk minority carrier lifetime (τbulk) is a critical parameter for solar cells but is difficult to determine in P–N junction devices, especially for high doping. As doping ≥1016 cm−3 is required for efficient drift‐charge‐carrier‐collection devices, a method for τbulk determination in doped P–N junction devices is necessary. This work utilizes time‐resolved photoluminescence (TRPL) simulations to quantify bulk and interface recombination properties in highly doped, graded absorber CdSeTe structures. The two methods developed here for τbulk determination include utilization of an instantaneous lifetime representation to guide TRPL fitting and direct comparison between measured and simulated decays. Simulations verified that both methods are valid for state‐of‐the‐art device architectures which include graded bandgap absorbers, graded doping, and graded lifetimes. Shifts in the dominant recombination mechanism are identified for sufficiently long τbulk, where front and back interface quality plays a more prominent role. Evaluation of surface recombination velocities and conduction band offset illustrate electro‐optical advantages of a positive conduction band offset and highlight the necessity of improved interfaces as bulk quality in photovoltaic devices improves. [ABSTRACT FROM AUTHOR]

This study explores the commitment of a school faculty to use the pedagogical practices needed to employ a project-based unit of science, technology, religion, engineering, arts, and mathematics (STREAM). The unit of study concentrated on environmental sustainability of butterflies through project-based learning (PBL). Teacher interviews were analyzed to reveal the similarities and differences, strengths, and weaknesses in the teachers' reactions to implementing a cross-curricula content unit designed for a pre-kindergarten (PK) to eighth grade school. Analysis of teacher data and classroom artifacts provided evidence of content mastery at the student levels, implementation of scaffolding for developmental levels, and the need for flexibility in scheduling. As a result of the study, the school leadership gained new perspectives regarding how the faculty understood and implemented STREAM programming. This study contributed to the knowledge base by informing teachers and educational leaders about the level of effectiveness STREAM can have within a K-8 school. [ABSTRACT FROM AUTHOR]

Background: Barriers to matriculation into Physician Assistant (PA) programs and entry into the PA profession have disproportionate impact on historically marginalized groups. This study evaluates if U.S. citizenship status is associated with likelihood of matriculation in PA Programs. Methods: Data from five Centralized Applicant Services for Physician Assistants (CASPA) admissions cycles (2012-2021) was evaluated cross-sectionally for the primary outcome of binary matriculation status (yes/no). Bivariate and multivariate logistic regression was utilized to investigate associations between self-identified U.S. citizenship status and likelihood of PA program matriculation. Models controlled for important potential confounders, including age, gender, race/ethnicity, non-native English speaker, patient care experience hours, total undergraduate grade point average (GPA), and number of applications submitted to various programs. Results: Non-U.S. citizen status was statistically associated with persistent lower likelihood of PA program matriculation compared to U.S. citizenship. Odds of matriculation were 41% [OR 0.59 (95% CI: 0.51, 0.68; p <.001)] to 51% [OR 0.49 (95% CI: 0.41, 0.58; p <.001)] lower in unadjusted models. Odds were 32% [OR 0.68 (95% CI: 0.56, 0.83; p <.001)] to 42% OR 0.58 (95% CI: 0.48, 0.71; p <.001) lower when adjusting for important covariates. The lowest likelihood occurred in 2012-2013 with 51% lower odds of matriculation and in 2016-2017 with 42% lower odds when accounting for important covariates. Discussion: PA programs are charged with improving diversity of clinically practicing PAs to improve health outcomes and better reflect patient populations. This analysis shows that non-U.S. citizenship may be a barrier to PA school acceptance. PA schools should raise awareness and create means and accessibility for admissions for this underrepresented group. [ABSTRACT FROM AUTHOR]

For structural assessment and optimal design of thick-section high-strength steels in applications under harsh service conditions, it is essential to understand the cleavage fracture micromechanisms. In this study, we assess the effects of through-thickness microstructure of an 80-mm-thick quenched and tempered S690 high-strength steel, notch orientation, and crack tip constraint in cleavage nucleation and propagation via sub-sized crack tip opening displacement (CTOD) testing at −100 °C. The notch was placed parallel and perpendicular to the rolling direction, and the crack tip constraint was analysed by varying the a/W ratio: 0.5, 0.25, and 0.1. The notch orientation does not play a role, and the material is considered isotropic in-plane. Nb-rich inclusions were observed to act as the weak microstructural link in the steel, triggering fracture in specimens with the lowest CTOD values. While shallow-cracked specimens from the top section present larger critical CTOD values than deep-cracked ones due to stress relief ahead of the crack tip, the constraint does not have a significant influence in the middle due to the very detrimental microstructure in the presence of Nb-rich inclusions. Some specimens show areas of intergranular fracture due to the combined effect of C, Cr, Mn, Ni, and P segregation along with precipitation of Nb-rich inclusions clusters on the grain boundaries. Several crack deflections at high-angle grain boundaries were observed where the neighbouring sub-structure has different Bain axes. [ABSTRACT FROM AUTHOR]

Preparing kinesiology undergraduates with the foundational knowledge required by professional organizations is no longer enough when considering the skills students are required to demonstrate upon entering the job market. Work-integrated learning, embedded through curricular and cocurricular activities, has seen extensive growth in the posteducation landscape of Canadian institutions. With increasing expectations from future employers, graduates in the field of kinesiology require more experiential opportunities to meet these expectations. The aim of this paper is to provide commentary on how the Bachelor of Kinesiology program at Capilano University underwent the necessary changes to incorporate a required professional practice stream to align with industry expectations. The authors discuss the development of laddering course learning outcomes, course content, reflection, and student evaluation. Additionally, they provide rationale for its inclusion in the second year of the program. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatitis C virus (HCV) therapy lowers risk of liver cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate immune response and pathogenesis of disease. We evaluated soluble markers of interferon signaling and liver cirrhosis, plasma miRNAs and other non-coding RNAs throughout HCV therapy prior to diagnosis of liver cancer to understand factors involved in the early stages of the cancer pathogenesis. Our results of the absence of cancer pathway suppressive miRNAs, in combination with serum immune biomarkers, may help enhance ability to identify patients at high risk for liver cancer and provide timely treatments. Background: Hepatitis C virus (HCV) therapy lowers risk of hepatocellular carcinoma (HCC). Little is known about factors driving/preceding HCC in treated persons. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate host response and pathogenesis of disease. We investigated plasma levels of these RNAs and select serum markers before, during, and after HCV therapy, preceding HCC. Methods: Of 187 DAA treated HCV patients where therapy oriented longitudinal sampling was performed at a time without HCC diagnosis, 9 were subsequently diagnosed with HCC within 2 years of therapy. They were matched with 7 patients not diagnosed with HCC over the same time period. RNASeq was performed on plasma, and serum was assessed for biomarkers of inflammation by ELISA. Results: HCC diagnosis was 19 months (6–28) after therapy start in the HCC group. 73 and 63 miRs were differentially expressed at baseline (before DAA therapy) and 12 weeks after DAA therapy comparing HCC and non-HCC groups. Several lncRNA- showed differential expression as well. Several miRNA suppressors of cancer-related pathways, lncRNA- and mRNA-derived stabilized short RNAs were consistently absent in the plasma of patients who developed HCC. Serum IP10, and MCP-1 level was higher in the HCC group 12 weeks after therapy, and distinct miRNAs correlated with IP10 and MCP-1. Finally, in a focused analysis of 8 miRNAs best associated with HCC we observed expression of mi576 and mi-5189 correlation with expression of a select group of PBMC mRNA. Conclusions: These results are consistent with complex interplay between RNA-mediated host immune regulation and cancer suppression, strikingly skewed 12 weeks following therapy, prior to HCC diagnosis. [ABSTRACT FROM AUTHOR]

Louisiana contains nearly 40% of estuarine herbaceous wetlands in the contiguous United States, supporting valuable ecosystem services and providing significant economic benefits to the state and the entire United States. However, coastal Louisiana is a hotspot for rapid land loss from factors including hurricanes, land use change, and high subsidence rates contributing to high relative sea‐level rise. The Coastal Protection and Restoration Authority (CPRA) was established after major hurricanes in 2005 to coordinate coastal restoration in Louisiana and develop the Louisiana Coastal Master Plan. The LA Coastal Master Plan uses numerical modeling of multiple scenarios to select a suite of restoration projects based on maximum land area created and flood reduction (as proxies for ecosystem value). Using potential value to aquatic, terrestrial, and social resources, our work compared habitat value of shallow open water areas to emergent wetland. While potential resource benefits varied by emergent wetland salinity type and emergent wetland versus water, they were similar, suggesting that restoration planning based primarily on wetland land area may not achieve the maximum possible ecosystem benefits. After nearly 20 years of integrated restoration planning in coastal Louisiana, a reassessment of restoration planning decision drivers may be beneficial to ensure maximum benefits from coastal restoration. As a result of the Deepwater Horizon oil spill, settlement funds will be a major support to coastal restoration in Louisiana for many years. Assessing potential habitat value to multiple natural and social resources in Louisiana has potential to maximize synergy with large northern Gulf of Mexico restoration programs. [ABSTRACT FROM AUTHOR]

Background: Elevated rheumatoid factor (RF) levels and systemic immune activation are highly prevalent during chronic hepatitis C virus (HCV) infection. Direct-acting antiviral (DAA) therapy has been associated with normalization of various soluble immune activation parameters. Whether the RF levels relate to soluble immune activation markers during chronic HCV infection, and over what time frame RF levels normalize during and after DAA treatment is unknown and was investigated here. Methods: In a longitudinal study, plasma and serum was obtained from HCV infected RF positive (RF+) and RF negative (RF-) participants. The levels of RF, HCV RNA and soluble markers of inflammation were determined before (week 0), during (weeks 4, 8 and 12) and after (week 24) treatment with HCV DAA therapy. In a subset of RF+ participants, the analysis was extended to over 70 weeks after therapy initiation. Hepatic and other clinical parameters were determined at baseline (week 0) in all participants. Results: Before therapy, transient elastography (TE) score was greater in RF+ compared to RF- HCV infected participants, while the systemic levels of soluble inflammatory markers were comparable. Following DAA therapy initiation, HCV RNA levels became undetectable within 4 weeks in both the RF+ and RF- groups. RF levels declined in the first 6 months in most RF+ persons but most commonly remained positive. The levels of some soluble inflammatory markers declined, mainly within 4 weeks of DAA therapy start, in both the RF+ and RF- groups. The baseline (week 0) TE score correlated with RF levels before, during and after DAA therapy, while plasma IL-18 levels correlated with RF level after DAA therapy. Conclusion: During chronic HCV infection, TE score is elevated in RF+ HCV infected individuals and factors other than HCV viremia (including liver stiffness or fibrosis and select markers of inflammation) likely contribute to persistence of RF after treatment of HCV with DAA. [ABSTRACT FROM AUTHOR]

Louisiana contains nearly 40% of estuarine herbaceous wetlands in the contiguous United States, supporting valuable ecosystem services and providing significant economic benefits to the state and the entire United States. However, coastal Louisiana is a hotspot for rapid land loss from factors including hurricanes, land use change, and high subsidence rates contributing to high relative sea‐level rise. The Coastal Protection and Restoration Authority (CPRA) was established after major hurricanes in 2005 to coordinate coastal restoration in Louisiana and develop the Louisiana Coastal Master Plan. The LA Coastal Master Plan uses numerical modeling of multiple scenarios to select a suite of restoration projects based on maximum land area created and flood reduction (as proxies for ecosystem value). Using potential value to aquatic, terrestrial, and social resources, our work compared habitat value of shallow open water areas to emergent wetland. While potential resource benefits varied by emergent wetland salinity type and emergent wetland versus water, they were similar, suggesting that restoration planning based primarily on wetland land area may not achieve the maximum possible ecosystem benefits. After nearly 20 years of integrated restoration planning in coastal Louisiana, a reassessment of restoration planning decision drivers may be beneficial to ensure maximum benefits from coastal restoration. As a result of the Deepwater Horizon oil spill, settlement funds will be a major support to coastal restoration in Louisiana for many years. Assessing potential habitat value to multiple natural and social resources in Louisiana has potential to maximize synergy with large northern Gulf of Mexico restoration programs. [ABSTRACT FROM AUTHOR]

Purpose: It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I–III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. Methods: Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes Results: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p =.04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p =.05) and diabetes (p =.05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p =.01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. Conclusion: Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients. [ABSTRACT FROM AUTHOR]

Macroscale cleavage fracture toughness of high strength steels is strongly related to the fracture of hard microstructural inclusions. Therefore, an accurate determination of the local stress on these inclusions based on the matrix stress is necessary for the statistical modelling of macroscale cleavage fracture. This paper presents analytical equations to quantitatively estimate the stress of the microstructural inclusions from the far-field stress of the matrix. The analytical equations account for the inclusion shape, the inclusion orientation, the far-field stress state and matrix material properties. Finite element modelling of a representative volume element containing a hard inclusion shows that the equations provide an accurate representation of the local stress state. The equations are implemented into a multi-barrier model and compared with CTOD experiments with two different levels of constraint. [ABSTRACT FROM AUTHOR]

By virtue of their licenses, local television stations in the United States must serve in the public interest of their communities. Because many stations' ownership is by corporate conglomerates, however, that public interest is often considered secondary to revenue maximization. Labor is exploited to meet this goal, with technology deployed in newsrooms to consolidate job descriptions, replace human labor with computers, and add sales-ready content platforms, while drawing as much surplus value from workers as possible. This study sought out newsroom employees, including rarely-studied behind the scenes personnel, in the 25 largest metropolitan areas of the country to find out how this utilization of technology affected their journalistic work routines and output. Their responses via online surveys and semi-structured interviews highlight the challenges of juggling ever-increasing tech-enabled job responsibilities while still providing quality reports for their audiences in a corporate ownership environment focused on profits. [ABSTRACT FROM AUTHOR]

Background: A primary rehabilitation goal for individuals with motor incomplete spinal cord injury (iSCI) is to regain walking abilities and return to community-level ambulation. Outside of quantitative indicators, little evidence exists to inform therapists in assisting patients in navigating community mobility method decisions. Objectives: Describe the factors included in the choice between walking or using wheeled mobility methods in the community for individuals with motor iSCI who have the capacity to walk. Design: A qualitative, grounded theory design was used to address the study aim. Methods: Seven individuals of varying chronicity and physical capacity with iSCI participated in one-on-one semi-structured interviews. Interviews were recorded, transcribed, coded, and organized into themes and subcategories to develop the theory of how individuals make mobility method decisions. Results: Individuals with iSCI described the factors they consider when choosing to walk, use wheeled mobility, or avoid community mobility altogether. Informants described a process of planning before any community outing that considered assessment of their body structures and functions, the task demands, and the environmental barriers and facilitators. Their perspectives on disability also influenced their mobility method choices. [ABSTRACT FROM AUTHOR]

Purpose of Review: Systemic inflammation increases as a consequence of aging (inflammaging) and contributes to age-related morbidities. Inflammation in people living with HIV is elevated compared with the general population even after prolonged suppression of viremia with anti-retroviral therapy. Mechanisms that contribute to inflammation during aging and in treated HIV disease are potentially interactive, leading to an exaggerated inflammatory phenotype in people with HIV. Recent Findings: Recent studies highlight roles for anti-retroviral therapy, co-infections, immune system alterations, and microbiome perturbations as important contributors to HIV-associated inflammation. These factors likely contribute to increased risk of age-related morbidities in people living with HIV. Summary: Understanding mechanisms that exaggerate the inflammaging process in people with HIV may lead to improved intervention strategies, ultimately, extending both lifespan and healthspan. [ABSTRACT FROM AUTHOR]

Background: The mechanisms underlying naïve CD4+ lymphopenia during chronic Hepatitis C Virus (HCV) infection are unclear. Whether direct-acting antiviral (DAA) therapy restores peripheral naïve CD4+ T cell numbers and function is unknown. Methods: We enumerated frequencies and counts of peripheral naïve CD4+, CD4+CD31+ and CD4+CD31- T cells by flow cytometry in a cross sectional analysis comparing chronic HCV infected (n=34), DAA-treated(n=29), and age-range matched controls (n=25), as well as in a longitudinal cohort of HCV DAA treated persons (n=16). The cross-sectional cohort was stratified by cirrhosis state. Cell apoptosis/survival (AnnexinV+7AAD+/BCL-2 labeling) and cell cycle entry (Ki67 expression) of CD31+ and CD31- naïve CD4+ T cells was analyzed directly ex vivo and following 3 and 5 days of in vitro culture with media, interleukin (IL) -7 or CD3/CD28 activator. Results: In the cross-sectional cohort, naïve CD4+ proportions were lower in chronic HCV infected persons compared to controls and DAA-treated persons, an effect in part attributed to cirrhosis. Age was associated with naïve cell counts and proportions in HCV infected and treated persons as well. Naïve CD4+ cell proportions negatively correlated with plasma levels of soluble CD14 following therapy in DAA-treated persons. Naïve CD4+ cells from HCV infected persons exhibited greater direct ex vivo apoptosis and cell-cycling compared to cells from DAA-treated persons and controls, and this was localized to the CD4+CD31+ subset. On the other hand, no remarkable differences in expression of BCL-2 or IL-7 Receptor (CD127) at baseline or following in vitro media or IL7 containing culture were observed. In the longitudinal cohort, naïve CD4+CD31+/CD31- ratio tended to increase 24 weeks after DAA therapy initiation. Conclusions: Activation and apoptosis of peripheral naïve CD4+CD31+ T cells appear to contribute to naïve CD4+ lymphopenia in chronic HCV infection, and this defect is partially reversible with HCV DAA therapy. Age and cirrhosis -associated naïve CD4+ lymphopenia is present both before and after HCV DAA therapy. These findings have implications for restoration of host immune function after DAA therapy. [ABSTRACT FROM AUTHOR]

Background: Immune non-responders (INR) are HIV+, ART-controlled (>2 yrs) people who fail to reconstitute their CD4 T cell numbers. Systemic inflammation and markers of T cell senescence and exhaustion are observed in INR. This study aims to investigate T cell senescence and exhaustion and their possible association with soluble immune mediators and to understand the immune profile of HIV-infected INR. Selected participants were <50 years old to control for the confounder of older age. Methods: Plasma levels of IL-6, IP10, sCD14, sCD163, and TGF-β and markers of T cell exhaustion (PD-1, TIGIT) and senescence (CD57, KLRG-1) were measured in ART-treated, HIV+ participants grouped by CD4 T cell counts (n = 63). Immune parameters were also measured in HIV-uninfected, age distribution-matched controls (HC; n = 30). Associations between T cell markers of exhaustion and senescence and plasma levels of immune mediators were examined by Spearman rank order statistics. Results: Proportions of CD4 T cell subsets expressing markers of exhaustion (PD-1, TIGIT) and senescence (CD57, KLRG-1) were elevated in HIV+ participants. When comparing proportions between INR and IR, INR had higher proportions of CD4 memory PD-1+, EM CD57+, TEM TIGIT+ and CD8 EM and TEM TIGIT+ cells. Plasma levels of IL-6, IP10, and sCD14 were elevated during HIV infection. IP10 was higher in INR. Plasma TGF-β levels and CD4 cycling proportions of T regulatory cells were lower in INR. Proportions of CD4 T cells expressing TIGIT, PD-1, and CD57 positively correlated with plasma levels of IL-6. Plasma levels of TGF-β negatively correlated with proportions of TIGIT+ and PD-1+ T cell subsets. Conclusions: INR have lower levels of TGF-β and decreased proportions of cycling CD4 T regulatory cells and may have difficulty controlling inflammation. IP10 is elevated in INR and is linked to higher proportions of T cell exhaustion and senescence seen in INR. [ABSTRACT FROM AUTHOR]

Coastal marshes are essential habitats for soil carbon accumulation and burial, which can influence the global carbon budget. Coastal Louisiana has extensive marsh habitats (fresh, intermediate, brackish, and saline) where soil cores were collected to a depth of 100 cm at 24 sites to assess long‐term carbon accumulation and burial rates. Select soil depth intervals were analyzed for bulk density, total carbon, and radionuclide (137Cs and 210Pb) dating. Marsh habitat maps (years 1949–2013) were also used to determine the most frequently occurring habitat at each field site. Over 5 decades, half of the sites transitioned between marsh habitats at least once. Saline marshes tended to have lower mean total carbon density (0.04 ± 0.002 g cm−3) and lower mean long‐term total carbon accumulation rates (211 ± 46 g TC m−2 yr−1, n = 5, based on 210Pb) compared to the other marsh habitats. Using marsh habitat specific accumulation rates and area, the total carbon burial rate for coastal Louisiana in year 2013 was estimated at 4.3 Tg TC yr−1 which accounts for about 5%–21% of the estimated tidal wetland burial rate globally. Historically, about 1.0 Tg TC yr−1 was lost due to reduced marsh area from 1949 to 2013. With no coastal restoration activity, the predicted wetland loss over the next 50 years could reduce carbon burial in coastal Louisiana to 2.1 Tg TC yr−1, a reduction of about 50% from the year 2013 rate, with potential to significantly alter the global carbon budget. Key Points: Marsh habitat soils in coastal Louisiana accumulate on average 211–381 g TC m−2 year−1 over the long term (decades)Louisiana marsh soils bury 4.3 Tg TC year−1, accounting for 5%–21% of global, 47% of North America, and 65% of Gulf of Mexico ratesHalf of the current soil carbon sink in coastal Louisiana marshes could be lost in the next 50 years with no coastal restoration activity [ABSTRACT FROM AUTHOR]

Introduction: Variations in postnatal length of refrigerated, unfixed umbilical cords were studied over time to elucidate natural changes and times of stability. Methods: Length was measured in 132 cords following severance, repeated at varying timed intervals and studied by analysis of variance and regression analysis. Results: Data show immediate rapid initial phase shortening (mean 4.2+/-3.9 cm SD); an interval of lengthening; stable length at hours 3-4 following severance, a slower second phase shortening (mean 1.5+/-0.7 cm SD) beginning at 5 hours and peaking at 12 hours; and gradual lengthening to stable length after 23 hours. Overall, there was a significant net mean decrease of 3.49+/-2.29 cm SD. Shortening was greatest for intact long cord segments (p=0.0001), as much as 11 cm. Two highly significant models for predicting umbilical cord length at delivery (OL) were determined using the post-delivery lengths (Length) measured at different times following delivery (Hours), as follows: At ≤ 3 hours following delivery: OL=1.02xLength cm+1.11xHours At >3 hours following delivery: OL=1.07xLength+0.44xHours-0.01x(Hours)2 Conclusion: Cord lengths stabilized between hours 3-4 and after 23 hours following severance. Phase one shortening resembles vasoconstriction; phase two resembles rigor mortis. The models allow prediction of the original umbilical cord length at delivery, regardless of the time of measurement. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved.Methods: We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks.Results: Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point.Conclusions: During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation.Clinical Trials Registration: NCT02194998. [ABSTRACT FROM AUTHOR]

The authors regret that we unknowingly used erroneous bulk density data in Figs. 4 and 6 (panels b,c,e) that affected results in Fig. 7. [ABSTRACT FROM AUTHOR]

Human activities have released large quantities of neutral persistent organic pollutants (POPs) that may be biomagnified in food webs and pose health risks to wildlife, particularly top predators. Here we develop a global 3‐D ocean simulation for four polychlorinated biphenyls (PCBs) spanning a range of molecular weights and volatilities to better understand effects of climate‐driven changes in ocean biogeochemistry on the lifetime and distribution of POPs. Observations are most abundant in the Arctic Ocean. There, model results reproduce spatial patterns and magnitudes of measured PCB concentrations. Sorption of PCBs to suspended particles and subsequent burial in benthic marine sediment is the dominant oceanic loss process globally. Results suggest benthic sediment burial has removed 75% of cumulative PCB releases since the onset of production in 1930. Wind speed, light penetration, and ocean circulation exert a stronger and more variable influence on volatile PCB congeners with lower particle affinity such as chlorinated biphenyl‐28 and chlorinated biphenyl‐101. In the Arctic Ocean between 1992 and 2015, modeled evasion (losses) of the more volatile PCB congeners from the surface ocean increased due to declines in sea ice and changes in ocean circulation. By contrast, net deposition increased slightly for higher molecular weight congeners with stronger partitioning to particles. Our results suggest future climate changes will have the greatest impacts on the chemical lifetimes and distributions of volatile POPs with lower molecular weights. Key Points: Climate change will have the greatest impacts on the chemical lifetimes and distributions of volatile persistent organic pollutantsMarine sediment has sequestered 75% of cumulative releases of polychlorinated biphenyls since the onset of production in 1930Arctic sea ice retreat is likely to enhance losses of volatile congeners but increase net deposition of higher molecular weight congeners [ABSTRACT FROM AUTHOR]

Background The 6-Minute Walk Test (6MWT) is a common clinical assessment used to evaluate locomotor function in patients after stroke. Previous work suggests the 6MWT can estimate peak metabolic capacity (VO2peak) without cardiorespiratory assessments during graded exercise tests (GXTs), which may assist with exercise prescription. However, selected research also indicated increased heart rates (HRs) during 6MWTs beyond levels considered safe without GXTs. Objective The goal of this study was to examine cardiorespiratory responses during 6MWTs and GXTs in individuals with chronic stroke and their associations with demographic or clinical characteristics. Design The study used a cross-sectional observational design. Methods Cardiorespiratory responses were assessed during 6MWTs at self-selected velocity (SSV) and fastest velocity (FV), and during GXTs. Secondary assessments included the lower extremity Fugl-Meyer Assessment, Functional Gait Assessment, gait speeds, and daily stepping activity. Correlation and regression analyses were used to evaluate associations between locomotor performance, cardiorespiratory responses, and clinical and demographic characteristics. Results Average HRs during 6MWT-FV were 72% to 76% of the age-predicted maximum (HRmax), with 20% of participants exceeding 85% predicted HRmax. When normalized to HRs during GXTs, HRs during 6MWT-FV were 86% to 88% of observed HRmax. Primary predictors of increased HRs during 6MWTs were resting HR, body mass index, and daily stepping. Distance during 6MWT-FV was a significant predictor of VO2peak in combination with other variables. Electrocardiographic abnormalities were observed in >80% of participants at rest and 31% demonstrated distinct abnormalities during GXTs, which were not related to 6MWT or GXT performance. Limitations In addition to sample size, a primary limitation involved the ability to accurately predict or measure HRmax in patients with motor dysfunction after stroke. Conclusions Cardiac responses were higher than anticipated during 6MWTs and often exceeded recommended HR thresholds. Clinicians should closely monitor cardiorespiratory responses during 6MWTs. [ABSTRACT FROM AUTHOR]

The highly contagious foot-and-mouth disease virus (FMDV) afflicts cloven-hoofed animals, resulting in significant costs because of loss of trade and recovery from disease. We developed a sensitive, specific, and rapid competitive ELISA (cELISA) to detect serum antibodies to FMDV. The cELISA utilized a monoclonal blocking antibody specific for a highly conserved FMDV nonstructural 3B epitope, a recombinant mutant FMDV 3ABC coating protein, and optimized format variables including serum incubation for 90 min at 20–25°C. Samples from 16 animals experimentally infected with one FMDV serotype (A, O, Asia, or SAT-1) demonstrated early detection capacity beginning 7 d post-inoculation. All samples from 55 vesicular stomatitis virus antibody-positive cattle and 44 samples from cloven-hoofed animals affected by non-FMD vesicular diseases were negative in the cELISA, demonstrating 100% analytical specificity. The diagnostic sensitivity was 100% against sera from 128 cattle infected with isolates of all FMDV serotypes, emphasizing serotype-agnostic results. Diagnostic specificities of U.S. cattle (n = 1135) and swine (n = 207) sera were 99.4% and 100%, respectively. High repeatability and reproducibility were demonstrated with 3.1% coefficient of variation in percent inhibition data and 100% agreement using 2 kit lots and 400 negative control serum samples, with no difference between bench and biosafety cabinet operation. Negative results from vaccinated, uninfected cattle, pig, and sheep sera confirmed the DIVA (differentiate infected from vaccinated animals) capability. This rapid (<3 h), select agent–free assay with high sensitivity and specificity, DIVA capability, and room temperature processing capability will serve as a useful tool in FMDV surveillance, emergency preparedness, response, and outbreak recovery programs. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit.Methods: We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection.Results: Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise.Conclusions: HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of ‘immune cold’ TNBCs. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the obstetrical and virological outcomes in HIV-infected pregnant women who delivered at a district general hospital in south London in the period from 2008 to 2014. Our review identified 137 pregnancies; most (60%, 63/105) of them were unplanned. The commonest mode of delivery was spontaneous vaginal delivery (SVD) (42%, 48/114) followed by emergency Caesarean section (32%, 36/114). Gestational age at delivery was ≥37 weeks in most (84%, 91/106) of the cases. Maternal HIV VL at or closest to delivery was undetectable (<40 copies/mL), <400 copies/mL and >1000 copies/mL in 73% (94/129), 90% (116/129) and 6% (8/129) of the pregnancies, respectively. None of the infants were infected with HIV making the rate of MTCT of HIV 0% (zero). Our study shows that favourable virological and obstetrical outcomes of HIV-infected pregnant women are achievable in non-tertiary HIV treatment centres. Impact Statement What is already known on this subject: Prevention of mother-to-child transmission (MTCT) of HIV has been one of the major public health successes in the last decades. This success was evident by the reduction of MTCT of HIV in the UK from 25.6% in the 1993 to only 0.46% in 2011. Furthermore, many reports from individual providers, mainly from tertiary centres, of HIV care in the UK also showed very low rates MTCT of HIV. What the results of this study add: Our study shows that favourable virological and obstetrical outcomes of HIV-infected pregnant women are achievable in non-tertiary HIV treatment centres. The MTCT of HIV rate in our hospital was zero in the period from 2008 to 2014. What the implications are of these findings for clinical practice and/or further research: Staff caring for pregnant HIV positive women in general hospitals and small-to-medium HIV clinics should liaise closely with each other and utilise the skill-mix within their hospital in order to provide a quality care that is similar to what is achieved in large teaching centres; however, a prompt referral to tertiary hospitals, when indicated, should be facilitated. [ABSTRACT FROM AUTHOR]

Purpose: Length dependence of post-activation potentiation (PAP) is a well-established phenomenon in animal models but less certain in intact whole human muscles. Recent advances in B-mode ultrasonography provide real-time imaging and evaluation of human muscle fascicles in vivo, thus removing the assumption that joint positioning alters fascicle length and influences the extent of PAP. The purpose of this study was to determine whether a conditioning maximal voluntary contraction (MVC) would influence the return of medial gastrocnemius (MG) fascicles to baseline length and alter the extent of twitch potentiation between three ankle positions.Methods: Ultrasonography was used to measure MG fascicle length for baseline and potentiated twitches at angles of 10° dorsiflexion (DF), 0° neutral (NEU-tibia perpendicular to the sole of the foot), and 20° plantar flexion (PF). A MVC was used as a conditioning contraction and PAP determined for each ankle angle.Results: PAP of the plantar flexors was greater in PF (28.8 ± 2.6%) compared to NEU (19.8 ± 1.8%; p < 0.05) and DF (9.3 ± 2.8%; p < 0.0001). In PF, fascicle lengths (4.64 ± 0.17 cm) were shorter than both NEU (5.78 ± 0.15 cm; p < 0.0001) and DF (6.09 ± 0.15 cm; p < 0.0001). Fascicle lengths for the baseline twitches were longer (5.92 ± 0.11 cm) than the potentiated twitches (5.83 ± 0.10 cm; p < 0.01) at all joint angles.Conclusion: Although PAP is greatest in PF compared to NEU and DF, the higher PAP in the PF joint angle cannot be attributed to fascicles remaining shortened following the MVC because across all joint positions, fascicles are similarly shortened following the MVC. [ABSTRACT FROM AUTHOR]