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American Samoa is experiencing rapid relative sea level rise due to increases in global sea level and significant post-2009 earthquake land subsidence, endangering homes and critical infrastructure. Wave and water-level observations collected over a fringing reef at Faga‘itua Bay, American Samoa, in 2017 reveal depth-limited shoreline sea-swell wave heights over the range of conditions sampled. Using field data to calibrate a one-dimensional, phase-resolving nonhydrostatic wave model (SWASH), we examine the influence of water level on wave heights over the reef for a range of current and future sea levels. Assuming a fixed reef bathymetry, model results predict rising sea levels will escalate nearshore extreme water levels that are dominated by an increase in nearshore sea-swell wave heights. Model results provide insight into how and at what reef depths rising sea levels reduce reef capacity to dissipate wave energy, compounding shoreline threats. This study aims to bring increased attention to the immediate threats to American Samoa’s way of life, and to demonstrate the utility of SWASH for extrapolating wave transformation to future sea level.

Rising groundwater tables due to sea level rise (SLR) pose a critical but understudied threat to low‐lying coastal regions. This study uses field observations and dynamic modeling to investigate drivers of groundwater variability and to project flooding risks from emergent groundwater in Imperial Beach, California. Hourly groundwater table data from four monitoring wells (2021–2024) reveal distinct aquifer behaviors across soil types. In transmissive coastal sandy soils, groundwater levels are dominated by ocean tides, with secondary contributions from non‐tidal sea level variability and seasonal recharge. In this setting, we calibrated an empirical groundwater model to observations, and forced the model with regional SLR scenarios. We project that groundwater emergence along the low‐lying coastal road will begin by the 2060s under intermediate SLR trajectories, and escalate to near‐daily flooding by 2100. Over 20% of San Diego County's coastline shares similar transmissive sandy geology and thus similar flooding risk. Results underscore the urgency of integrating groundwater hazards into coastal resilience planning, as current adaptation strategies in Imperial Beach—focused on surface flooding—are insufficient to address infrastructure vulnerabilities from below. This study provides a transferable framework for assessing groundwater‐driven flooding in transmissive coastal aquifers, where SLR‐induced groundwater rise threatens critical infrastructure decades before permanent inundation. Plain Language Summary Rising groundwater levels caused by sea level rise could flood coastal communities before oceans permanently cover the land. In Imperial Beach, California, a low‐lying city already facing coastal flooding, we studied how tides, ocean levels, and rainfall affect groundwater. Near the beach, sandy soils allow ocean tides to push groundwater up and down daily. A model created using data from groundwater wells predicts that rising seas will cause groundwater to emerge onto roads and other low‐lying areas during high tides by the 2060s. By 2100, flooding could occur almost daily. Over 20% of San Diego County's coastline has similar sandy soils, meaning many communities face this hidden risk. Current community plans focusing on flooding from ocean waves and storms do not consider rising groundwater, leaving roads, pipes, and buildings vulnerable to damage from below. Our findings call for urgent updates to coastal planning to address this threat. The approach used here can help other coastal towns identify where and when groundwater flooding may become a critical issue. Key Points Coastal groundwater levels in Imperial Beach, California, are driven by ocean tides, non‐tidal sea level variability, and recharge Rising groundwater tables from sea level rise will drive significant coastal flooding in Imperial Beach by mid to late century Coastal resilience plans must integrate groundwater emergence risks to avoid ineffective flood mitigation

Coastal systems face unprecedented challenges from sea level rise (SLR), threatening natural mechanisms that dissipate ocean wave energy and regulate shoreline stability. This dissertation integrates three critical lines of investigation to assess how SLR disrupts coastal protection systems across spatial and temporal scales. First, groundwater observation and modeling reveals that sea level rise is projected to exacerbate coastal flooding through subsurface emergence in Imperial Beach, California by the end of the century. Second, hydrodynamic analysis of a reef in American Samoa demonstrates that SLR reduces reef dissipation of nearshore sea-swell wave energy. If reefs are unable to dissipate incident sea-swell energy due to SLR, places like American Samoa will need to prepare for dramatic increases in wave run-up and nearshore wave forces. Third, satellite-derived shoreline analyses of O‘ahu, Hawai‘i, demonstrate that interannual sea level variability drives interannual beach width change for many of O‘ahu’s beaches. The increased shoreline sea-swell variability due to SLR modeled in American Samoa may drive increases in sandy beach shoreline erosion around many shorelines of O‘ahu. These findings collectively highlight the need for adaptive strategies that address groundwater flooding, reef degradation, and sediment dynamics as interconnected components of coastal resilience.

Background This study illustrates the use of logistic regression and machine learning methods, specifically random forest models, in health services research by analyzing outcomes for a cohort of patients with concomitant peripheral artery disease and diabetes mellitus. Methods Cohort study using fee-for-service Medicare beneficiaries in 2015 who were newly diagnosed with peripheral artery disease and diabetes mellitus. Exposure variables include whether patients received preventive measures in the 6 months following their index date: HbA1c test, foot exam, or vascular imaging study. Outcomes include any reintervention, lower extremity amputation, and death. We fit both logistic regression models as well as random forest models. Results There were 88,898 fee-for-service Medicare beneficiaries diagnosed with peripheral artery disease and diabetes mellitus in our cohort. The rate of preventative treatments in the first six months following diagnosis were 52% ( n  = 45,971) with foot exams, 43% ( n  = 38,393) had vascular imaging, and 50% ( n  = 44,181) had an HbA1c test. The directionality of the influence for all covariates considered matched those results found with the random forest and logistic regression models. The most predictive covariate in each approach differs as determined by the t-statistics from logistic regression and variable importance (VI) in the random forest model. For amputation we see age 85 + (t = 53.17) urban-residing (VI = 83.42), and for death (t = 65.84, VI = 88.76) and reintervention (t = 34.40, VI = 81.22) both models indicate age is most predictive. Conclusions The use of random forest models to analyze data and provide predictions for patients holds great potential in identifying modifiable patient-level and health-system factors and cohorts for increased surveillance and intervention to improve outcomes for patients. Random forests are incredibly high performing models with difficult interpretation most ideally suited for times when accurate prediction is most desirable and can be used in tandem with more common approaches to provide a more thorough analysis of observational data.

Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical detection of melioidosis in humans is primarily by culturing B. pseudomallei, and there are no standardized detection protocols for NHP. NHP are an important animal model for melioidosis research including clinical trials and development of biodefense countermeasures. We evaluated the diagnostic potential of the multiple antigen serological assay, BurkPx, in NHP using two sera sets: (i) 115 B. pseudomallei-challenged serum samples from 80 NHP collected each week post-exposure (n = 52) and at euthanasia (n = 47), and (ii) 126 B. pseudomallei-naïve/negative serum samples. We observed early IgM antibody responses to carbohydrate antigens followed by IgG antibody recognition to multiple B. pseudomallei protein antigens during the second week of infection. B. pseudomallei negative serum samples had low to intermediate antibody cross reactivity to the antigens in this assay. Infection time was predicted as the determining factor in the variation of antibody responses, with 77.67% of variation explained by the first component of the principal component analysis. A multiple antigen model generated a binary prediction metric ([Formula: see text]), which when applied to all data resulted in 100% specificity and 63.48% sensitivity. Removal of week 1 B. pseudomallei challenged serum samples increased the sensitivity of the model to 95%. We employed a previously standardized assay for humans, the BurkPx assay, and assessed its diagnostic potential for detection of B. pseudomallei exposure in NHP. The assay is expected to be useful for surveillance in NHP colonies, in investigations of suspected accidental releases or exposures, and for identifying vaccine correlates of protection.

Abstract Rationale Pulmonary arterial hypertension (PAH) is a medically incurable disease resulting in death from right ventricular (RV) failure. Both pulmonary vascular and RV remodeling are linked to dynamic changes in the microvasculature. Therefore, we hypothesized that circulating angiostatic factors could be linked to outcomes and represent novel biomarkers of disease severity in PAH. Objectives We sought to determine the relationship of a potent angiostatic factor, endostatin (ES), with disease severity and mortality in PAH. Furthermore, we assessed genetic predictors of ES expression and/or function and their association with outcomes in PAH. Methods We measured levels of serum ES in two independent cohorts of patients with PAH. Contemporaneous clinical data included New York Heart Association functional class, 6-minute-walk distance, invasive hemodynamics, and laboratory chemistries. Measurements and Main Results Serum ES correlated with poor functional status, decreased exercise tolerance, and invasive hemodynamics variables. Furthermore, serum ES was a strong predictor of mortality. A loss-of-function, missense variant in the gene encoding ES, Col18a1, was linked to lower circulating protein and was independently associated with reduced mortality. Conclusions Our data link increased expression of ES to disease severity in PAH and demonstrate a significant relationship with adverse outcomes. Circulating ES levels can be genetically influenced, implicating ES as a genetically determined modifier of disease severity impacting on survival. These observations support serum ES as a potential biomarker in PAH with the capacity to predict poor outcomes. More importantly, this study implicates Col18a1/ES as a potential new therapeutic target in PAH.

Background Optic nerve sheath diameters (ONSD) have been validated as an accurate screening tool to detect elevated intracranial pressure in hypertensive encephalopathy. The neurologic manifestations of preeclampsia and/or eclampsia mimic those of hypertensive encephalopathy. This study was performed to assess the incidence of elevated optic nerve sheath diameters of patients with severe preeclampsia and neurologic criteria compared to non-preeclamptic patients. The secondary objective was to determine baseline optic nerve sheath diameters in patients with severe preeclampsia without neurologic criteria and preeclampsia without severe features. Methods Single site cohort study including 62 pregnant women 18 years or older and 20 weeks or further gestation. Patients with preeclampsia without severe features, preeclampsia with severe features by non-neurologic criteria, preeclampsia with severe features with neurologic criteria, and patients without preeclampsia were enrolled via convenience sampling. One blinded reviewer measured sheath diameters; baseline demographics and pregnancy data were collected by chart review. Statistical analysis was completed with STATA/IC 16. Categorical variables were compared by the χ 2  test. Continuous variables were presented as mean ± standard deviation, and discrete variables were presented as medians and compared by Kruskal–Wallis testing. Normality was confirmed by Shapiro–Wilk testing. Linear and logistic regression were used to test the association between the preeclampsia groups and optic nerve sheath diameters. Models were presented as unadjusted and adjusted for BMI, gestation, hypertension, diabetes, parity, and gravidity. Results The incidence of optic nerve sheath diameters > 5.8 mm was 43.8% in the severe preeclampsia with neurologic features cohort, and 42.1% in the control cohort, with a relative risk of 1.04. Patients with severe preeclampsia without neurologic features had sheath diameters of 5.75 mm ± 1.09 mm; non-severe preeclampsia patients had sheath diameters of 5.54 mm ± 1.26 mm. Conclusions We did not find a significant elevated optic nerve sheath diameter relative risk between severe preeclampsia patients with neurologic features and non-preeclampsia control patients. This is the first study to assess a North American population utilizing ACOG criteria for severe and non-severe preeclampsia, with severe cohorts additionally stratified by neurologic criteria.

Current antiretroviral therapy (ART) for HIV/AIDS slows disease progression by reducing viral loads and increasing CD4 counts. Yet ART is not curative due to the persistence of CD4+ T-cell proviral reservoirs that chronically resupply active virus. Elimination of these reservoirs through the administration of synergistic combinations of latency reversing agents (LRAs), such as histone deacetylase (HDAC) inhibitors and protein kinase C (PKC) modulators, provides a promising strategy to reduce if not eradicate the viral reservoir. Here, we demonstrate that largazole and its analogues are isoform-targeted histone deacetylase inhibitors and potent LRAs. Significantly, these isoform-targeted HDAC inhibitors synergize with PKC modulators, namely bryostatin-1 analogues (bryologs). Implementation of this unprecedented LRA combination induces HIV-1 reactivation to unparalleled levels and avoids global T-cell activation within resting CD4+ T-cells.

This study examined how the Australian news media have portrayed public hospital Emergency Departments (EDs) over the last two decades. A systematic review and media frame analysis, searching Factiva and Australia and New Zealand News Stream for digital and print news articles published between January 2000 and January 2020. Eligibility criteria were (1) discussed EDs in public hospitals; (2) the primary focus of the article was the ED; (3) focused on the Australian context; (4) were published by one of the Australian state-based news outlets (e.g., The Sydney Morning Herald, Herald Sun). A pair of reviewers independently screened 242 articles for inclusion according to the pre-established criteria. Discrepancies were resolved via discussion. 126 articles met the inclusion criteria. Pairs of independent reviewers identified frames in 20% of the articles using an inductive approach to develop a framework for coding the remaining articles. News media rely heavily on reporting problems within and with the ED, while also proposing a cause. Praise for EDs was minimal. Opinions were primarily from government spokespeople, professional associations, and doctors. ED performance was often reported as fact, with no reference to the source of the information. Rhetorical framing devices, such as hyperbole and imagery, were used to emphasise dominant themes. The negative bias inherent in news media reporting of EDs could potentially damage public awareness of ED functioning, with implications for the likelihood of the public’s accessing ED services. Like in the film Groundhog Day, news media reporting is stuck in a loop reporting the same narrative over and over again.

Abstract Background Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV)–infected individuals globally. Screening for TB at the point of HIV diagnosis with a high-sensitivity assay presents an opportunity to reduce mortality. Methods We performed a cluster randomized trial of TB screening among adults newly diagnosed with HIV in 12 primary health clinics in rural Thyolo, Malawi. Clinics were allocated in a 1:1 ratio to perform either point-of-care Xpert MTB/RIF assay (Xpert) or point-of-care light-emitting diode fluorescence microscopy (LED-FM) for individuals screening positive for TB symptoms. Asymptomatic participants were offered isoniazid preventive therapy in both arms. Investigators, but not clinic staff or participants, were masked to allocation. Our primary outcome was the incidence rate ratio (RR) of all-cause mortality within 12 months of HIV diagnosis. Results Prevalent TB was diagnosed in 24 of 1001 (2.4%) individuals enrolled in clinics randomized to Xpert, compared with 10 of 841 (1.2%) in clinics randomized to LED-FM. All-cause mortality was 22% lower in the Xpert arm than in the LED-FM arm (6.7 vs 8.6 per 100 person-years; RR, 0.78 [95% confidence interval {CI}, .58–1.06]). A planned subgroup analysis suggested that participants with more advanced HIV (World Health Organization clinical stage 3 or 4) disease had lower mortality in clinics randomized to Xpert than to LED-FM (RR, 0.43 [95% CI, .22–.87]). Conclusions In rural Malawi, using point-of-care Xpert MTB/RIF to test symptomatic patients for TB at the time of HIV diagnosis reduced all-cause 12-month mortality among individuals with advanced HIV. Clinical Trials Registration NCT01450085. In this randomized trial of screening for tuberculosis among adults in rural Malawi with newly diagnosed HIV, all-cause mortality was 22% lower overall, and 57% lower among participants with clinically advanced HIV, when using point-of-care Xpert MTB/RIF vs point-of-care fluorescence microscopy.