A phase II study of potentiation of pembrolizumab with binimetinib and bevacizumab in refractory microsatellite stable colorectal cancer.

PURPOSE: In this single-institution phase II investigator-initiated study we assessed the ability of MAPK and VEGF pathway blockade to overcome resistance to immunotherapy in microsatellite stable metastatic colorectal cancer (MSS mCRC). PATIENTS AND METHODS: Patients with MSS, BRAF wild-type mCRC who progressed on ≥2 prior lines of therapy received pembrolizumab, binimetinib, and bevacizumab until disease progression or unacceptable toxicity. After a safety run-in, patients were randomized to a 7-day run-in of binimetinib or simultaneous initiation of all study drugs, to explore whether MEK inhibition may increase tumor immunogenicity. The primary endpoint was objective response rate in all patients combined (ORR, by RECIST v1.1). RESULTS: Fifty patients received study drug treatment; 54% were male with median age 55 years (range 31-79). The primary endpoint, ORR, was 12.0% (95% confidence interval [CI] 4.5-24.3%), which was not statistically different than the historical control data of 5% (p=0.038, exceeding pre-specified threshold of 0.025). The disease control rate was 70.0% (95% CI 55.4-82.1%), median progression-free survival 5.9 months (95% CI 4.2-8.7 months), and median overall survival 9.3 months (95% CI 6.7-12.2 months). No difference in efficacy was observed between the randomized cohorts. Grade 3 and 4 adverse events were observed in 56% and 8% of patients, respectively; the most common were rash (12%) and increased aspartate aminotransferase (12%). CONCLUSION: Pembrolizumab, binimetinib, and bevacizumab failed to meet its primary endpoint of higher ORR compared to historical control data, demonstrated a high disease control rate, and demonstrated acceptable tolerability in refractory MSS mCRC.

All tidal wetlands are blue carbon ecosystems.

Managing coastal wetlands is one of the most promising activities to reduce atmospheric greenhouse gases, and it also contributes to meeting the United Nations Sustainable Development Goals. One of the options is through blue carbon projects, in which mangroves, saltmarshes, and seagrass are managed to increase carbon sequestration and reduce greenhouse gas emissions. However, other tidal wetlands align with the characteristics of blue carbon. These wetlands are called tidal freshwater wetlands in the United States, supratidal wetlands in Australia, transitional forests in Southeast Asia, and estuarine forests in South Africa. They have similar or larger potential for atmospheric carbon sequestration and emission reductions than the currently considered blue carbon ecosystems and have been highly exploited. In the present article, we suggest that all wetlands directly or indirectly influenced by tides should be considered blue carbon. Their protection and restoration through carbon offsets could reduce emissions while providing multiple cobenefits, including biodiversity.

Long-Term Outcomes Following Definitive or Adjuvant Proton Radiotherapy for Adenoid Cystic Carcinoma.

Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT). Materials and Methods: Under an institutional review board-approved, single-institutional prospective outcomes registry, we reviewed the records of 56 patients with de novo, nonmetastatic ACC of the head and neck treated with PT with definitive (n = 9) or adjuvant PT (n = 47) from June 2007 to December 2021. The median dose to the primary site was 72.6 gray relative biological equivalent (range, 64-74.4) delivered as either once (n = 19) or twice (n = 37) daily treatments. Thirty patients received concurrent chemotherapy. Thirty-one patients received nodal radiation, 30 electively and 1 for nodal involvement. Results: With a median follow-up of 6.2 years (range, 0.9-14.7), the 5-year local-regional control (LRC), disease-free survival, cause-specific survival, and overall survival rates were 88%, 85%, 89%, and 89%, respectively. Intracranial extension (P = .003) and gross residual tumor (P = .0388) were factors associated with LRC rates. While the LRC rate for those with a gross total resection was 96%, those with subtotal resection or biopsy alone were 81% and 76%, respectively. The 5-year cumulative incidence of clinically significant grade ≥3 toxicity was 15%, and the crude incidence at the most recent follow-up was 23% (n = 13). Conclusion: This is the largest sample size with the longest median follow-up to date of patients with ACC treated with PT. PT can provide excellent disease control for ACC of the head and neck with acceptable toxicity. T4 disease, intracranial involvement, and gross residual disease at the time of PT following either biopsy or subtotal resection were significant prognostic features for worse outcomes.

Development and analyses of stakeholder driven conceptual models to support the implementation of ecosystem-based fisheries management in the U.S. Caribbean.

Fisheries management agencies in the U.S. Caribbean are currently taking steps into transitioning from a single species approach to one that includes Ecosystem Based Fisheries Management (EBFM) considerations. In this study, we developed and analyzed stakeholder-driven conceptual models with seven different stakeholder groups in Puerto Rico and the US Virgin Islands to assess and compare their perceptions of the fishery ecosystem. Conceptual models were developed for each stakeholder group during 29 separate workshops involving a total of 236 participants representing Commercial Fishers, Managers, Academics, Local Businesses, Environmental NGOs, and the Caribbean Fishery Management Council (CFMC) District Advisory Panels (DAPs) and Scientific and Statistical Committee (SSC). Non-Metric Multidimensional Scaling (nMDS) and two-mode social network analysis were used to investigate differences and similarities between stakeholder groups as well as to identify priority ecosystem elements and threats. Results show important variations between stakeholders and islands in terms of their perceived importance of ecosystem components and relationships, which supports the need for collaborative approaches and co-production of knowledge in the United States (U.S.) Caribbean region. Despite this variation, important areas of common concern among stakeholders were identified such as: habitat integrity (e.g., coral reefs), water quality, and influence of recreational fisheries and tourism on marine ecosystems. Findings of this study support the use of stakeholder-driven conceptual models as effective tools to guide decision-making, aid prioritization of data collection, and increase collaboration and cooperation among stakeholders in the context of fisheries management.

Assessment of salivary cortisol dynamics in an infantry training exercise: a pilot study.

INTRODUCTION: Measuring cortisol during military training offers insights into physiological responses to stress. We attempted precisely timed, cortisol awakening response (CAR) and pre-sleep cortisol (PSC), and diurnal slope (peak morning minus evening cortisol), during a British Army exercise. We aimed to understand cortisol dynamics and evaluate the feasibility of CAR and PSC in this environment. METHOD: Setting: high-intensity, 10-day infantry exercise. Participants: regular infantry soldiers exercising (EX, n=25) or headquarters-based (HQ, n=6). Participants undertook PSC and WAKE and WAKE+30 min samples after 1-2 days, 5-6 days and 9-10 days. Wrist-worn GENEActiv accelerometers were used to assess sleep duration in EX only. Samples taken ±15 min from prespecified time points were deemed adherent. Validated questionnaires were used to measure resilience and perceived stress. Cortisol and cortisone were measured simultaneously by liquid chromatography tandem mass spectrometry. RESULTS: From adherent participants' samples, CAR was positive and tended to decrease as the exercise progressed. From all available data, HQ demonstrated greater diurnal slope than EX (F=7.68, p=0.02), reflecting higher morning cortisol (F=4.72, p=0.038) and lower PSC (p=0.04). No differences were seen in cortisol:cortisone ratio. 26.1% of CAR samples were adherent, with moderately strong associations between adherence and stress (r=0.41, p=0.009) but no association between adherence and day of exercise (χ2=0.27, p=0.8), sleep duration (r=-0.112, p=0.43) or resilience (r=-0.79, p=0.75). Test-retest reliability ratings for CAR were Cronbach's α of 0.48, -11.7 and 0.34 for the beginning, middle and end of the exercise, respectively. CONCLUSIONS: We observed a reduction in morning cortisol and decreased diurnal slope during a high-intensity military exercise, compared with the HQ comparator cohort in whom diurnal slope was preserved. A carefully timed CAR was not feasible in this setting.

FXR Agonism with Bile Acid Mimetic Reduces Pre-Clinical Triple-Negative Breast Cancer Burden.

Bariatric surgery is associated with improved outcomes for several cancers, including breast cancer (BC), although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Patients with greater expression of the bile acid receptor FXR displayed improved survival in specific aggressive BC subtypes. FXR is a nuclear hormone receptor activated by primary bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would induce anticancer effects. Using in vivo and in vitro approaches, we determined the anti-tumor potential of bile acid receptor agonism. Indeed, FXR agonism by the bile acid mimetic known commercially as Ocaliva ("OCA"), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. The transcriptomic analysis of tumors in mice subjected to OCA treatment revealed differential gene expression patterns compared to vehicle controls. Notably, there was a significant down-regulation of the oncogenic transcription factor MAX (MYC-associated factor X), which interacts with the oncogene MYC. Gene set enrichment analysis (GSEA) further demonstrated a statistically significant downregulation of the Hallmark MYC-related gene set (MYC Target V1) following OCA treatment. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, the synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor TGR5 (GPBAR1) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. These findings suggest that FXR is a tumor suppressor gene with a high potential for use in personalized therapeutic strategies for individuals with BC.

Examination of Wnt signaling as a therapeutic target for pancreatic ductal adenocarcinoma (PDAC) using a pancreatic tumor organoid library (PTOL).

Pancreatic ductal adenocarcinoma (PDAC) presents at advanced stages and is refractory to most treatment modalities. Wnt signaling activation plays a critical role in proliferation and chemotherapeutic resistance. Minimal media conditions, growth factor dependency, and Wnt dependency were determined via Wnt inhibition for seven patient derived organoids (PDOs) derived from pancreatic tumor organoid libraries (PTOL). Organoids demonstrating response in vitro were assessed in vivo using patient-derived xenografts. Wnt (in)dependent gene signatures were identified for each organoid. Panc269 demonstrated a trend of reduced organoid growth when treated with ETC-159 in combination with paclitaxel or gemcitabine as compared with chemotherapy or ETC-159 alone. Panc320 demonstrated a more pronounced anti-proliferative effect in the combination of ETC-159 and paclitaxel but not with gemcitabine. Panc269 and Panc320 were implanted into nude mice and treated with ETC-159, paclitaxel, and gemcitabine as single agents and in combination. The combination of ETC-159 and paclitaxel demonstrated an anti-tumor effect greater than ETC-159 alone. Extent of combinatory treatment effect were observed to a lesser extent in the Panc320 xenograft. Wnt (in)dependent gene signatures of Panc269 and 320 were consistent with the phenotypes displayed. Gene expression of several key Wnt genes assessed via RT-PCR demonstrated notable fold change following treatment in vivo. Each pancreatic organoid demonstrated varied niche factor dependencies, providing an avenue for targeted therapy, supported through growth analysis following combinatory treatment of Wnt inhibitor and standard chemotherapy in vitro. The clinical utilization of this combinatory treatment modality in pancreatic cancer PDOs has thus far been supported in our patient-derived xenograft models treated with Wnt inhibitor plus paclitaxel or gemcitabine. Gene expression analysis suggests there are key Wnt genes that contribute to the Wnt (in)dependent phenotypes of pancreatic tumors, providing plausible mechanistic explanation for Wnt (in)dependency and susceptibility or resistance to treatment on the genotypic level.

Prediction of Nanoparticle Photoreactivity in Mixtures of Surface Foulants Requires Kinetic (Non-equilibrium) Adsorption Considerations.

The adsorption of foulants on photocatalytic nanoparticles can suppress their reactivity in water treatment applications by scavenging reactive species at the photocatalyst surface, screening light, or competing for surface sites. These inhibitory effects are commonly modeled using the Langmuir-Hinshelwood model, assuming that adsorbed layer compositions follow Langmuirian (equilibrium) competitive adsorption. However, this assumption has not been evaluated in complex mixtures of foulants. This study evaluates the photoreactivity of titanium dioxide (TiO2) nanoparticles toward a target compound, phenol, in the presence of two classes of foulants ─ natural organic matter (NOM) and a protein, bovine serum albumin (BSA) ─ and mixtures of the two. Langmuir adsorption models predict that BSA should strongly influence the nanoparticle photoreactivity because of its higher adsorption affinity relative to phenol and NOM. However, model evaluation of the experimental phenol decay rates suggested that neither the phenol nor foulant surface coverages are governed by Langmuirian competitive adsorption. Rather, a reactivity model incorporating kinetic predictions of adsorbed layer compositions (favoring NOM adsorption) outperformed Langmuirian models in providing accurate, unbiased predictions of phenol degradation rates. This research emphasizes the importance of using first-principles models that account for adsorption kinetics when assumptions of equilibrium adsorption do not apply.

Population-level comparisons of gene regulatory networks modeled on high-throughput single-cell transcriptomics data.

Single-cell technologies enable high-resolution studies of phenotype-defining molecular mechanisms. However, data sparsity and cellular heterogeneity make modeling biological variability across single-cell samples difficult. Here we present SCORPION, a tool that uses a message-passing algorithm to reconstruct comparable gene regulatory networks from single-cell/nuclei RNA-sequencing data that are suitable for population-level comparisons by leveraging the same baseline priors. Using synthetic data, we found that SCORPION outperformed 12 existing gene regulatory network reconstruction techniques. Using supervised experiments, we show that SCORPION can accurately identify differences in regulatory networks between wild-type and transcription factor-perturbed cells. We demonstrate SCORPION's scalability to population-level analyses using a single-cell RNA-sequencing atlas containing 200,436 cells from colorectal cancer and adjacent healthy tissues. The differences between tumor regions detected by SCORPION are consistent across multiple cohorts as well as with our understanding of disease progression, and elucidate phenotypic regulators that may impact patient survival.

Overcoming doxorubicin resistance in triple-negative breast cancer using the class I-targeting HDAC inhibitor bocodepsin/OKI-179 to promote apoptosis.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a poor prognosis. Doxorubicin is part of standard curative therapy for TNBC, but chemotherapy resistance remains an important clinical challenge. Bocodepsin (OKI-179) is a small molecule class I histone deacetylase (HDAC) inhibitor that promotes apoptosis in TNBC preclinical models. The purpose of this study was to investigate the combination of bocodepsin and doxorubicin in preclinical TNBC models and evaluate the impact on terminal cell fate, including apoptosis and senescence. METHODS: TNBC cell lines were treated with doxorubicin and CellTiter-Glo was used to assess proliferation and determine doxorubicin sensitivity. Select cell lines were treated with OKI-005 (in vitro version of bocodepsin) and doxorubicin and assessed for proliferation, apoptosis as measured by Annexin V/PI, and cell cycle by flow cytometry. Immunoblotting was used to assess changes in mediators of apoptosis, cell cycle arrest, and senescence. Senescence was measured by the senescence-associated ß-galactosidase assay. An MDA-MB-231 xenograft in vivo model was treated with bocodepsin, doxorubicin, or the combination and assessed for inhibition of tumor growth. shRNA knockdown of p53 was performed in the CAL-51 cell line and proliferation, apoptosis and senescence were assessed in response to combination treatment. RESULTS: OKI-005 and doxorubicin resulted in synergistic antiproliferative activity in TNBC cells lines regardless of p53 mutation status. The combination led to increased apoptosis and decreased senescence. In vivo, the combination resulted in increased tumor growth inhibition compared to either single agent. shRNA knock-down of p53 led to increased doxorubicin-induced senescence that was decreased with the addition of OKI-005 in vitro. CONCLUSION: The addition of bocodepsin to doxorubicin resulted in synergistic antiproliferative activity in vitro, improved tumor growth inhibition in vivo, and promotion of apoptosis which makes this a promising combination to overcome doxorubicin resistance in TNBC. Bocodepsin is currently in clinical development and has a favorable toxicity profile compared to other HDAC inhibitors supporting the feasibility of evaluating this combination in patients with TNBC.

Using waste biomass to produce 3D-printed artificial biodegradable structures for coastal ecosystem restoration.

The loss of ecosystem functions and services caused by rapidly declining coastal marine ecosystems, including corals and bivalve reefs and wetlands, around the world has sparked significant interest in interdisciplinary methods to restore these ecologically and socially important ecosystems. In recent years, 3D-printed artificial biodegradable structures that mimic natural life stages or habitat have emerged as a promising method for coastal marine restoration. The effectiveness of this method relies on the availability of low-cost biodegradable printing polymers and the development of 3D-printed biomimetic structures that efficiently support the growth of plant and sessile animal species without harming the surrounding ecosystem. In this context, we present the potential and pathway for utilizing low-cost biodegradable biopolymers from waste biomass as printing materials to fabricate 3D-printed biodegradable artificial structures for restoring coastal marine ecosystems. Various waste biomass sources can be used to produce inexpensive biopolymers, particularly those with the higher mechanical rigidity required for 3D-printed artificial structures intended to restore marine ecosystems. Advancements in 3D printing methods, as well as biopolymer modifications and blending to address challenges like biopolymer solubility, rheology, chemical composition, crystallinity, plasticity, and heat stability, have enabled the fabrication of robust structures. The ability of 3D-printed structures to support species colonization and protection was found to be greatly influenced by their biopolymer type, surface topography, structure design, and complexity. Considering limited studies on biodegradability and the effect of biodegradation products on marine ecosystems, we highlight the need for investigating the biodegradability of biopolymers in marine conditions as well as the ecotoxicity of the degraded products. Finally, we present the challenges, considerations, and future perspectives for designing tunable biomimetic 3D-printed artificial biodegradable structures from waste biomass biopolymers for large-scale coastal marine restoration.

Discrepancies in Mass Shootings and Access to Trauma Care Across the United States, 2014-2018.

INTRODUCTION: The United States has one of the highest rates of gun violence and mass shootings. Timely medical attention in such events is critical. The objective of this study was to assess geographic disparities in mass shootings and access to trauma centers. METHODS: Data for all Level I and II trauma centers were extracted from the American College of Surgeons and the Trauma Center Association of America registries. Mass shooting event data (4+ individuals shot at a single event) were taken from the Gun Violence Archive between 2014 and 2018. RESULTS: A total of 564 trauma centers and 1672 mass shootings were included. Ratios of the number of mass shootings vs trauma centers per state ranged from 0 to 11.0 mass shootings per trauma center. States with the greatest disparity (highest ratio) included Louisiana and New Mexico. CONCLUSION: States in the southern regions of the US experience the greatest disparity due to a high burden of mass shootings with less access to trauma centers. Interventions are needed to increase access to trauma care and reduce mass shootings in these medically underserved areas.

Purpose in life as a resilience factor for brain health: diffusion MRI findings from the Midlife in the U.S. study.

Introduction: A greater sense of purpose in life is associated with several health benefits relevant for active aging, but the mechanisms remain unclear. We evaluated if purpose in life was associated with indices of brain health. Methods: We examined data from the Midlife in the United States (MIDUS) Neuroscience Project. Diffusion weighted magnetic resonance imaging data (n=138; mean age 65.2 years, age range 48-95; 80 females; 37 black, indigenous, and people of color) were used to estimate microstructural indices of brain health such as axonal density, and axonal orientation. The seven-item purpose in life scale was used. Permutation analysis of linear models was used to examine associations between purpose in life scores and the diffusion metrics in white matter and in the bilateral hippocampus, adjusting for age, sex, education, and race. Results and discussion: Greater sense of purpose in life was associated with brain microstructural features consistent with better brain health. Positive associations were found in both white matter and the right hippocampus, where multiple convergent associations were detected. The hippocampus is a brain structure involved in learning and memory that is vulnerable to stress but retains the capacity to grow and adapt through old age. Our findings suggest pathways through which an enhanced sense of purpose in life may contribute to better brain health and promote healthy aging. Since purpose in life is known to decline with age, interventions and policy changes that facilitate a greater sense of purpose may extend and improve the brain health of individuals and thus improve public health.

Assessing the reliability of biomechanical variables during a horizontal deceleration task in healthy adults.

Horizontal deceleration technique is an underpinning factor to musculoskeletal injury risk and performance in multidirectional sport. This study primarily assessed within- and between-session reliability of biomechanical and performance-based aspects of a horizontal deceleration technique and secondarily investigated the effects of limb dominance on reliability. Fifteen participants completed four horizontal decelerations on each leg during test and retest sessions. A three-dimensional motion analysis system was used to collect kinetic and kinematic data. Completion time, ground contact time, rate of horizontal deceleration, minimum centre of mass height, peak eccentric force, impulse ratio, touchdown distance, sagittal plane foot and knee angles at initial contact, maximum sagittal plane thorax angle, and maximum knee flexion moment were assessed. Coefficients of variation (COV) and intraclass correlation coefficients (ICC) were used to assess within- and between-session reliability, respectively. Seven variables showed "great" within-session reliability bilaterally (COV ≤9.13%). ICC scores were 'excellent' (≥0.91; n = 4), or 'good' (0.76-0.89; n = 7), bilaterally. Limb dominance affected five variables; three were more reliable for the dominant leg. This horizontal deceleration task was reliable for most variables, with little effect of limb dominance on reliability. This deceleration task may be reliably used to assess and track changes in deceleration technique in healthy adults.

Resting EEG Periodic and Aperiodic Components Predict Cognitive Decline Over 10 Years.

Measures of intrinsic brain function at rest show promise as predictors of cognitive decline in humans, including EEG metrics such as individual α peak frequency (IAPF) and the aperiodic exponent, reflecting the strongest frequency of α oscillations and the relative balance of excitatory/inhibitory neural activity, respectively. Both IAPF and the aperiodic exponent decrease with age and have been associated with worse executive function and working memory. However, few studies have jointly examined their associations with cognitive function, and none have examined their association with longitudinal cognitive decline rather than cross-sectional impairment. In a preregistered secondary analysis of data from the longitudinal Midlife in the United States (MIDUS) study, we tested whether IAPF and aperiodic exponent measured at rest predict cognitive function (N = 235; age at EEG recording M = 55.10, SD = 10.71) over 10 years. The IAPF and the aperiodic exponent interacted to predict decline in overall cognitive ability, even after controlling for age, sex, education, and lag between data collection time points. Post hoc tests showed that "mismatched" IAPF and aperiodic exponents (e.g., higher exponent with lower IAPF) predicted greater cognitive decline compared to "matching" IAPF and aperiodic exponents (e.g., higher exponent with higher IAPF; lower IAPF with lower aperiodic exponent). These effects were largely driven by measures of executive function. Our findings provide the first evidence that IAPF and the aperiodic exponent are joint predictors of cognitive decline from midlife into old age and thus may offer a useful clinical tool for predicting cognitive risk in aging.

Prioritising plastic pollution research in blue carbon ecosystems: A scientometric overview.

The Blue Carbon Ecosystems (BCEs), comprising mangroves, saltmarshes, and seagrasses, located at the land-ocean interface provide crucial ecosystem services. These ecosystems serve as a natural barrier against the transportation of plastic waste from land to the ocean, effectively intercepting and mitigating plastic pollution in the ocean. To gain insights into the current state of research, and uncover key research gaps related to plastic pollution in BCEs, this study conveyed a comprehensive overview using bibliometric, altmetric, and literature synthesis approaches. The bibliometric analysis revealed a significant increase in publications addressing plastic pollution in BCEs, particularly since 2018. Geographically, Chinese institutions have made substantial contributions to this research field compared to countries and regions with extensive BCEs and established blue carbon science programs. Furthermore, many studies have focused on mangrove ecosystems, while limited attention was given to exploring plastic pollution in saltmarsh, seagrass, and multiple ecosystems simultaneously. Through a systematic analysis, this study identified four major research themes in BCE-plastics research: a) plastic trapping by vegetated coastal ecosystems, b) microbial plastic degradation, c) ingestion of plastic by benthic organisms, and d) effects of plastic on blue carbon biogeochemistry. Upon synthesising the current knowledge in each theme, we employed a perspective lens to outline future research frameworks, specifically emphasising habitat characteristics and blue carbon biogeochemistry. Emphasising the importance of synergistic research between plastic pollution and blue carbon science, we underscore the opportunities to progress our understanding of plastic reservoirs across BCEs and their subsequent effects on blue carbon sequestration and mineralisation. Together, the outcomes of this review have overarching implications for managing plastic pollution and optimising climate mitigation outcomes through the blue carbon strategies.

Resting EEG Periodic and Aperiodic Components Predict Cognitive Decline Over 10 Years.

Measures of intrinsic brain function at rest show promise as predictors of cognitive decline in humans, including EEG metrics such as individual alpha peak frequency (IAPF) and the aperiodic exponent, reflecting the strongest frequency of alpha oscillations and the relative balance of excitatory:inhibitory neural activity, respectively. Both IAPF and the aperiodic exponent decrease with age and have been associated with worse executive function and working memory. However, few studies have jointly examined their associations with cognitive function, and none have examined their association with longitudinal cognitive decline rather than cross-sectional impairment. In a preregistered secondary analysis of data from the longitudinal Midlife in the United States (MIDUS) study, we tested whether IAPF and aperiodic exponent measured at rest predict cognitive function (N = 235; age at EEG recording M = 55.10, SD = 10.71) over 10 years. The IAPF and the aperiodic exponent interacted to predict decline in overall cognitive ability, even after controlling for age, sex, education, and lag between data collection timepoints. Post-hoc tests showed that "mismatched" IAPF and aperiodic exponents (e.g., higher exponent with lower IAPF) predicted greater cognitive decline compared to "matching" IAPF and aperiodic exponents (e.g., higher exponent with higher IAPF; lower IAPF with lower aperiodic exponent). These effects were largely driven by measures of executive function. Our findings provide the first evidence that IAPF and the aperiodic exponent are joint predictors of cognitive decline from midlife into old age and thus may offer a useful clinical tool for predicting cognitive risk in aging.

Laryngological Complaint Prevalence in Hypermobile Ehlers-Danlos or Hypermobility Spectrum Disorders.

OBJECTIVE: The aim was to study laryngological complaints in patients with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSD). METHODS: A total of 363 patients met inclusion for the study by completing questions related to voice, upper airway, and swallowing between July 7, 2020 and July 13, 2022. Demographic data, voice-related questions, and hypermobility diagnosis were analyzed retrospectively. From those, 289 patients were diagnosed with hEDS or HSD with 74 that did not meet the diagnostic criteria for either diagnosis serving as controls. RESULTS: There were no statistically significant differences between patients with hEDS and HSD regarding Voice Handicap Index (VHI-10) scores, voice, upper airway, or swallow complaints. However, more hEDS/HSD patients answered positively to the laryngeal dysfunction question versus controls (p = 0.031). 22.5% of hEDS/HSD patients (n = 65) reported hoarseness, of which 52.3% reported hoarseness >2 days/month. 33.9% (n = 98) with hEDS/HSD reported symptoms of dysphagia, and 27.0% (n = 78) reported laryngeal dysfunction symptoms. Controls demonstrated 20.3% prevalence of hoarseness, of which 46.7% reported hoarseness >2 days/month. 24.3% of controls had dysphagia and 14.9% laryngeal dysfunction symptoms. Of the 363 patients, VHI-10 scores >11 were more likely in patients reporting >2 days of hoarseness/month (p = 0.001) versus those with <2 days of hoarseness/month. There was an increased prevalence of voice, upper airway, and dysphagia symptoms in hEDS/HSD patients compared with previously reported prevalence data in the general population. CONCLUSION: A significant proportion of patients diagnosed with hypermobility due to hEDS or HSD were found to have voice, upper airway, and dysphagia symptoms. These rates are higher than those previously reported in the general population. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:773-778, 2024.

Using a human-factors engineering approach to evaluate environmental cleaning in Veterans' Affairs acute and long-term care facilities: A qualitative analysis.

BACKGROUND: Environmental cleaning is important in the interruption of pathogen transmission. Although prevention initiatives have targeted environmental cleaning, practice variations exist and compliance is low. Evaluation of human factors influencing variations in cleaning practices can be valuable in developing interventions to standardized practices. We conducted a work-system analysis using a human-factors engineering (HFE) framework to identify barriers and facilitators to environmental cleaning practices in acute and long-term care settings within the Veterans' Affairs health system. METHODS: We conducted a qualitative study with key stakeholders at 3 VA facilities. We analyzed transcripts for thematic content and mapped themes to the HFE framework. RESULTS: Staffing consistency was felt to improve cleaning practices and teamwork. We found that many environmental management service (EMS) staff were veterans who were motivated to serve fellow veterans, especially to prevent infections. However, hiring veterans comes with regulatory hurdles that affect staffing. Sites reported some form of monitoring their cleaning process, but there was variation in method and frequency. The EMS workload was affected by whether rooms were occupied by patients or were semiprivate rooms; both were reportedly more difficult to clean. Room design and surface finishes were identified as important to cleaning efficiency. CONCLUSION: HFE work analysis identified barriers and facilitators to environmental cleaning. These findings highlight intervention entry points that may facilitate standardized work practices. There is a need to develop task-specific procedures such as cleaning occupied beds and semiprivate rooms. Future research should evaluate interventions that address these determinants of environmental cleaning.