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Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. Methods: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. Results: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85–1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63–0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08–1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. Conclusions: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04894877.

Abstract. The purpose of this study was to better understand effects of video game rewards on information processing using neuroimaging techniques. Excitation transfer theory, with the limited capacity model of motivated mediated messages, was used to predict that game rewards (administered through goal-directed spatial decision-making demands) will increase hippocampal activity. Activity will remain heightened in a subsequent declarative memory task. It was also predicted that heightened hippocampal activity during encoding will result in better recall after a 25-min delay. Both hypotheses were supported. Participants who played the goal-directed spatial decision-making game experienced greater hippocampal activation during the encoding phase of the memory task. And they demonstrated better recall for the encoded information after the delay. There was also a negative correlation between hippocampal activation and a primary inhibitory neurotransmitter, gamma-aminobutyric acid. These results suggest that goal-directed spatial decision-making mechanics can be important for facilitating hippocampal activation and declarative memory. They stress the need for future research to consider how these mechanics could be implemented in games for learning or as a potential intervention technique for those with memory impairments.

Post-transplant diabetes mellitus (PTDM) is common following heart transplant, impacting greater than 20% of patients with most cases occurring in the first year after transplant. PTDM is associated with multiple negative sequelae including increased post-operative infections, a higher rate of renal failure, and increased mortality. Compared with pre-transplant diabetes mellitus, PTDM has several unique risk factors and immunosuppressive medications play an important role in disease pathophysiology. Newer treatments for hyperglycemia, including glucagon like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, may counter the mechanisms of immunosuppression-related hyperglycemia making them an appealing treatment option for patients with PTDM. Here, we review the definitions, incidence, risk factors, pathophysiology, clinical outcomes, treatment options, pharmacologic considerations, and future directions in PTDM.

A polygenic risk score (PGS) is associated with obstructive coronary artery disease (CAD) independent of traditional risk factors. Coronary computed tomography angiography (CTA) can characterize coronary plaques, including features of highrisk CAD. However, it is unknown if a PGS is associated with obstructive CAD and high-risk CAD phenotypes in patients with symptoms suggestive of CAD.

In South Carolina (SC), 42% of youth are overweight or obese. Two sets of modifiable behaviors contributing to obesity are physical activity (PA) and dietary habits. School-based interventions have successfully improved these behaviors. The purpose of this study was to identify SC public school personnel perspectives on the most common barriers and facilitators to regular PA and healthy eating behaviors in schools.A needs assessment survey was conducted with school personnel statewide. There were 17 questions on the survey that addressed: (1) demographic information about participants' educational backgrounds, (2) barriers to regular PA and healthy eating behaviors in schools, and (3) facilitators to regular PA and healthy eating behaviors in schools. Univariate and bivariate descriptive statistical analyses were performed using IBM SPSS Statistics 27.Participants (N = 1311) indicated insufficient time for regular PA (n = 514, 39.2%) and limited access to healthy foods for healthy eating (n = 271, 20.7%) as main barriers. The primary facilitators were support from administrators for regular PA (n = 264, 20.1%) and support from cafeteria staff for healthy eating (n = 234, 17.8%). Further analyses explored how factors compared based on roles in schools, academic levels, and school district classifications.Results suggest that overarching barriers and facilitators to school-based interventions addressing childhood obesity exist, so common strategies to mitigate challenges and maximize supports can be used in schools. Future studies are needed to examine how decreasing barriers and enhancing facilitators affect the implementation and outcomes of these school-based interventions.

The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial randomized participants with chronic coronary disease (CCD) to guideline-directed medical therapy with or without angiography and revascularization. The study examined the association of nonadherence with health status outcomes.The study sought to compare 12-month health status outcomes of adherent and nonadherent participants with CCD with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management.Self-reported medication-taking behavior was assessed at randomization with a modified 4-item Morisky-Green-Levine Adherence Scale, and participants were classified as adherent or nonadherent. Twelve-month health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ-7) summary score (SS), which ranges from 0 to 100 (higher score = better). The association of adherence with outcomes was evaluated using Bayesian proportional odds models, including an interaction by study arm (conservative vs invasive).Among 4,480 randomized participants, 1,245 (27.8%) were nonadherent at baseline. Nonadherent participants had worse baseline SAQ-7 SS in both conservative (72.9 ± 19.3 vs 75.6 ± 18.4) and invasive (71.0 ± 19.8 vs 74.2 ± 18.7) arms. In adjusted analyses, adherence was associated with higher 12-month SAQ-7 SS in both treatment groups (mean difference in SAQ-7 SS with conservative treatment = 1.6 [95% credible interval: 0.3-2.9] vs with invasive management = 1.9 [95% credible interval: 0.8-3.1]), with no interaction by treatment.More than 1 in 4 participants reported medication nonadherence, which was associated with worse health status in both conservative and invasive treatment strategies at baseline and 12 months. Strategies to improve medication adherence are needed to improve health status outcomes in CCD, regardless of treatment strategy. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Objective To integrate an auto-notification system into clinical workflow, so timely communication of sentinel events (elective surgery, hospital admission, or ER visit) in immunosuppressed rheumatic disease patients happened by design. Methods We developed an algorithm that triggered auto-notification within the electronic medical record to rheumatology when a patient experienced a sentinel event. A telephone encounter was created that included event type, baseline therapy, and event date. This was forwarded to the rheumatologist, who recorded guideline-driven recommendations and returned it to nursing. Instructions were included to communicate recommendations to the patient, inpatient rheumatology team, or other clinician. This was studied over four months at a multi-specialty medical practice in Central Pennsylvania. Primary outcomes were percentage of total notifications, notifications by sentinel event type where a change in care plan was recommended, as well as percentage of time where rheumatologists were notified of sentinel events, compared to prior to the intervention. Secondary outcomes were staff work effort. Results 240 notifications were received - 57% for elective surgeries, 39% for ER visits, and 4% for admissions. The need for change in care plan was only 17% for ER visits but was 25% for hospital admissions and 44% for elective surgeries. The percentage of time rheumatologists were notified of events increased from 57.6% to 100%. The average number of messages received per week was 2.2, requiring a weekly average of 13 minutes of work per physician. Conclusion We developed an easy, well-received process that "hardwires" rheumatologist notification sentinel events to facilitate timely care.

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported.We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death.Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy.In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.

BACKGROUND: The timing of antihypertensive drugs administration is controversial. The aim was to compare the efficacy of dosing of antihypertensive drugs in the morning versus evening. METHODS: A PubMed, EMBASE, and clinicaltrials.gov databases search for randomized clinical trials of antihypertensive therapies where patients were randomized to morning versus evening dosing. The outcomes were ambulatory blood pressure parameters (day-time, night-time, and 24/48-hour systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and cardiovascular outcomes. RESULTS: Of 72 randomized controlled trials included, evening dosing significantly reduced ambulatory blood pressure parameters: 24/48-hour SBP (mean difference [MD]=1.41 mm Hg; [95% CI, 0.48–2.34]), DBP (MD=0.60 mm Hg [95% CI, 0.12–1.08]), night-time SBP (MD=4.09 mm Hg [95% CI, 3.01–5.16]), DBP (MD, 2.57 mm Hg [95% CI, 1.92–3.22]), with a smaller reduction in day-time SBP (MD=0.94 mm Hg [95% CI, 0.01–1.87]), and DBP (MD=0.87 mm Hg [95% CI, 0.10–1.63]), and numerically lower cardiovascular events compared with morning dosing. However, when controversial data by Hermida (23 trials, 25 734 patients) were omitted ( P heterogeneity CONCLUSIONS: Evening dosing of antihypertensive drugs significantly reduced ambulatory blood pressure parameters and lowered cardiovascular events but the effect was mainly driven by trials by Hermida group. Unless the intention is to specifically lower night-time blood pressure, antihypertensive drugs should be taken at a time of day that is convenient, optimizes adherence, and minimizes undesirable effects.

Background and objectiveThere are overwhelming health disparities in the Deep South. It is important to include the voice of communities affected by these disparities when developing interventions. The goal of the current study was to develop an academic community engaged partnership to strengthen the ability to address priority health concerns of rural African American communities with a focus on health literacy and health advocacy.MethodsA community-based participatory research approach was used to administer a 15-item community health survey in five rural communities led by African American mayors in Alabama (N = 752). The survey assessed the health concerns and the potential behaviors that may be associated with those health concerns.ResultsThe five communities demonstrated similarities as well as differences in both the health concerns endorsed and the potential health behaviors that may contribute to those concerns. All five communities identified cardiovascular disease as a health concern with three endorsing mental health issues and 2 dental health. With respect to behaviors, all five communities identified either unhealthy eating/exercise and substance use as concerns with one community identifying racism as a risky behavior affecting health.ConclusionThe results presented replicate CBPR studies demonstrating that communities are important sources of information about local health priorities and concerns.

Climate-driven permafrost thaw alters the strongly coupled carbon and nitrogen cycles within the Arctic tundra, influencing the availability of limiting nutrients including nitrate (NO3−). Researchers have identified two primary mechanisms that increase nitrogen and NO3− availability within permafrost soils: (1) the ‘frozen feast’, where previously frozen organic material becomes available as it thaws, and (2) ‘shrubification’, where expansion of nitrogen-fixing shrubs promotes increased soil nitrogen. Through the synthesis of original and previously published observational data, and the application of multiple geospatial approaches, this study investigates and highlights a third mechanism that increases NO3− availability: the hydrogeomorphic evolution of polygonal permafrost landscapes. Permafrost thaw drives changes in microtopography, increasing the drainage of topographic highs, thus increasing oxic conditions that promote NO3− production and accumulation. We extrapolate relationships between NO3− and soil moisture in elevated topographic features within our study area and the broader Alaskan Coastal Plain and investigate potential changes in NO3− availability in response to possible hydrogeomorphic evolution scenarios of permafrost landscapes. These approximations indicate that such changes could increase Arctic tundra NO3− availability by ~250–1000%. Thus, hydrogeomorphic changes that accompany continued permafrost degradation in polygonal permafrost landscapes will substantially increase soil pore water NO3− availability and boost future fertilization and productivity in the Arctic.

School-based interventions and strategies targeting physical activity (PA) and eating patterns have successfully addressed unhealthy behaviors contributing to excess weight in school-age children. The purpose of this study was to investigate South Carolina (SC) public school administrators' perceptions of and experiences with weight-related issues in schools and associated barriers and facilitators to awareness, selection, and implementation of school-based healthy PA and eating interventions and strategies.This qualitative descriptive study, guided by the Social Ecological Model and the Steps in Quality Intervention Development Model, involved semistructured interviews with SC public school administrators from all academic levels (N = 28). Data were analyzed using thematic analysis.Four themes were identified from interviews (N = 28): weight-related terminology or stigma, experiences with school-based healthy PA and eating interventions and strategies, barriers to school-based healthy PA and eating interventions and strategies, and facilitators to school-based healthy PA and eating interventions and strategies.Schools are well-positioned to provide interventions and strategies to improve PA and dietary habits leading to childhood obesity. School administrators, while knowledgeable and experienced with weight-related issues and school-based interventions and strategies, encounter barriers and facilitators that impact offerings and delivery. Understanding these challenges and supports is important in the development, adaptation, and implementation of school-based interventions and strategies focused on healthy PA and eating behaviors.

Climate change will alter the balance between frozen and thawed conditions in Arctic systems. Increased temperatures will make the extensive northern permafrost carbon stock vulnerable to decomposition and translocation. Production, cycling, and transport of dissolved organic carbon (DOC) are crucial processes for high-latitude ecosystem carbon loss that result in considerable export off the Arctic landscape. To identify where and under what conditions permafrost DOC is mobilized in an Arctic headwater catchment, we measured radiocarbon (14C) of DOC and assessed DOC composition with ultraviolet–visible spectroscopy (UV–Vis) of surface waters and shallow and deep subsurface porewaters from 17 drainages in the Barrow Environmental Observatory in Alaska. Samples were collected in July and September 2013 to assess changes in age and chemistry of DOC over time. DOC age was highly variable ranging from modern (19 ‰ Δ14C) to approximately 7000 BP (−583 ‰ Δ14C). DOC age increased with depth, over the summer as the active layer deepened, and with increasing drainage size. DOC quality indicators reflected a DOC source rich in high molecular-weight and aromatic compounds, characteristics consistent with vegetation-derived organic matter that had undergone little microbial processing, throughout the summer and a weak relationship with DOC age. In deep porewaters, DOC age was also correlated with several biogeochemical indicators (including dissolved methane concentration, δ13C, and the apparent fractionation factor), suggesting a coupling between carbon and redox biogeochemistry influencing methane production. In the drained thawed lake basins included in this study, DOC concentrations and contributions of vegetation-derived organic matter declined with increasing basin age. The weak relationship between DOC age and chemistry and consistency in DOC chemical indicators over the summer suggest a high lability of old DOC released by thawing permafrost.

Rh(OAc)2/HPW/SiO2 is an effective bifunctional catalyst for the halide-free carbonylation of methanol to methyl acetate and acetic acid.

Informal caregivers are an essential component of stroke survivor care, yet they are at risk for poorer outcomes due to their own unmet needs, feelings of isolation and abandonment, and lack of personal resources. While a substantial body of research literature on stroke caregiving exists, there is a notable research gap related to the specific needs of working age (18-64) stroke caregivers. The purpose of this study was to characterize unmet needs and concerns, caregiver self-efficacy, social support, and quality of life of working age caregivers of stroke survivors. A cross-sectional descriptive design was used. Participants (N=103) included family or friends that provided unpaid care for a stroke survivor outside of healthcare institutions recruited through national organizations, local support groups, and Facebook ads. Participants completed an online survey comprised of questions exploring sociodemographic characteristics, stroke survivor functional independence, perceived social support, and caregiver needs and concerns, strain, self-efficacy, and quality of life. Descriptive statistics and linear regression analysis were performed using the IBM Statistical Program for Social Sciences (SPSS) v28 software package. In individual regression models, stroke survivor functional independence, caregiver self-efficacy, perceived social support, race, gender, relationship with the stroke survivor, transportation, and responsibilities outside of the caregiving role were predictive of caregiver quality of life. In multiple regression models, stroke survivor functional independence, caregiver self-efficacy, race and gender were statistically significant predictors of caregiver quality of life. In conclusion, this study adds to the current literature by exploring unmet needs and concerns of working age caregivers of stroke survivors and relationships between caregiver quality of life and sociodemographic characteristics, stroke survivor functional independence, perceived social support, and caregiver needs and concerns, strain, and self-efficacy. A greater understanding of these needs can inform intervention designs to meet the unique needs of a diverse population of informal caregivers of stroke survivors.

We have developed a course-based undergraduate research experience (CURE) that can be carried out in the context of an existing second-semester or upper-level organic laboratory course. In this three-week laboratory module, students synthesize a small library of molecules, test them in a robust biological assay, and design a new compound library on the basis of their results.

Previous studies report hippocampal volume loss can help predict conversion from normative aging to mild cognitive impairment to dementia. Additionally, a growing literature indicates that stress-related allostatic load may increase disease vulnerability. The current study examined the relationship between stress-related cytokines (ie, interleukin-6 [IL-6]), cognition as measured by Mini-Mental State Examination (MMSE) scores, and hippocampal volume. Mixed models were employed to examine both within- (across time) and between-subject effects of IL-6 and hippocampal volume on MMSE score among 566 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The within-subject analysis found left hippocampal volume significantly (p = .009) predicted MMSE score. Between-subject analysis found the effect of IL-6 on MMSE was moderated by right hippocampal volume (p = .001). These results replicate previous findings and also extend prior work demonstrating stress-related cytokines may play a role in Alzheimer’s disease progression.

Recent investigations have identified water polo athletes as at risk for concussions and repetitive subconcussive head impacts. Head impact exposure in collegiate varsity women's water polo, however, has not yet been longitudinally quantified. We aimed to determine the relationship between cumulative and acute head impact exposure across pre-season training and changes in serum biomarkers of brain injury. Twenty-two Division I collegiate women's water polo players were included in this prospective observational study. They wore sensor-installed mouthguards during all practices and scrimmages during eight weeks of pre-season training. Serum samples were collected at six time points (at baseline, before and after scrimmages during weeks 4 and 7, and after the eight-week pre-season training period) and assayed for neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) using Simoa

Background In the ISCHEMIA trial, individuals randomized to the conservative strategy (CON) could undergo coronary catheterization (cath) for suspicion of an endpoint event, persistent symptoms despite optimal medical therapy, or through protocol non-adherence. Understanding the reasons for cath in CON participants can aid in ISCHEMIA results interpretation. Purpose To describe the frequency of and factors associated with early cath in ISCHEMIA CON participants. Methods A prespecified, post-hoc analysis of the 2591 CON participants was performed with multivariable analyses to identify independent factors associated with cath within 6 months of randomization (“early cath”). Results Overall 8.7% (225/2591) of CON participants underwent an early cath: with 4.6% (119/2591) for a suspected endpoint, 1.6% (41/2591) for medical treatment failure, and 2.6% (67/2591) for protocol non-adherence; 67% of all these caths (151/225) occurred within the first 3 months from randomization. Independent factors associated with cath among CON participants included daily (HR=5.84, CI: 2.73–12.47, p Conclusions The rate of early cath in the ISCHEMIA CON strategy was low and driven mainly by a suspected endpoint event. Severe/moderate baseline angina and quality of life impairment were independently associated with very early cath. Chances of early cath were greater with worsening pre-randomization angina and need for additional antianginal medication, and less with well controlled LDL-C and decreasing angina pattern. The baseline severity of ischemia or extent of disease on coronary imaging were not related to early cath. These results give important insight into the coronary disease treatment trajectory in the conservative strategy of the ISCHEMIA trial, further inform real-life decision making and point to the efficacy of optimal medical therapy in reducing the need for cath. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health, National Heart Lunch and Blood Institute

Previous studies have found that block play results in better spatial ability which may lead to greater mathematical skills. The current study examined a specific type of block play, structured blo...

The pathways and timing of drainage from the inundated centers of ice-wedge polygons in a warming climate have important implications for carbon flushing, advective heat transport, and transitions from methane to carbon dioxide dominated emissions. Here, we expand on previous research using a recently developed analytical model of drainage from a low-centered polygon. Specifically, we perform (1) a calibration to field data identifying necessary model refinements and (2) a rigorous model sensitivity analysis that expands on previously published indications of polygon drainage characteristics. This research provides intuition on inundated polygon drainage by presenting the first in-depth analysis of drainage within a polygon based on hydrogeological first principles. We verify a recently developed analytical solution of polygon drainage through a calibration to a season of field measurements. Due to the parsimony of the model, providing the potential that it could fail, we identify the minimum necessary refinements that allow the model to match water levels measured in a low-centered polygon. We find that (1) the measured precipitation must be increased by a factor of around 2.2, and (2) the vertical soil hydraulic conductivity must decrease with increasing thaw depth. Model refinement (1) accounts for runoff from rims into the ice-wedge polygon pond during precipitation events and possible rain gauge undercatch, while refinement (2) accounts for the decreasing permeability of deeper soil layers. The calibration to field measurements supports the validity of the model, indicating that it is able to represent ice-wedge polygon drainage dynamics. We then use the analytical solution in non-dimensional form to provide a baseline for the effects of polygon aspect ratios (radius to thaw depth) and coefficient of hydraulic conductivity anisotropy (horizontal to vertical hydraulic conductivity) on drainage pathways and temporal depletion of ponded water from inundated ice-wedge polygon centers. By varying the polygon aspect ratio, we evaluate the relative effect of polygon size (width), inter-annual increases in active-layer thickness, and seasonal increases in thaw depth on drainage. The results of our sensitivity analysis rigorously confirm a previous analysis indicating that most drainage through the active layer occurs along an annular region of the polygon center near the rims. This has important implications for transport of nutrients (such as dissolved organic carbon) and advection of heat towards ice-wedge tops. We also provide a comprehensive investigation of the effect of polygon aspect ratio and anisotropy on drainage timing and patterns, expanding on previously published research. Our results indicate that polygons with large aspect ratios and high anisotropy will have the most distributed drainage, while polygons with large aspect ratios and low anisotropy will have their drainage most focused near their periphery and will drain most slowly. Polygons with small aspect ratios and high anisotropy will drain most quickly. These results, based on parametric investigation of idealized scenarios, provide a baseline for further research considering the geometric and hydraulic complexities of ice-wedge polygons.

Deep-water access is arguably the most effective, but under-studied, mechanism that plants employ to survive during drought. Vulnerability to embolism and hydraulic safety margins can predict mortality risk at given levels of dehydration, but deep-water access may delay plant dehydration. Here, we tested the role of deep-water access in enabling survival within a diverse tropical forest community in Panama using a novel data-model approach. We inversely estimated the effective rooting depth (ERD, as the average depth of water extraction), for 29 canopy species by linking diameter growth dynamics (1990-2015) to vapor pressure deficit, water potentials in the whole-soil column, and leaf hydraulic vulnerability curves. We validated ERD estimates against existing isotopic data of potential water-access depths. Across species, deeper ERD was associated with higher maximum stem hydraulic conductivity, greater vulnerability to xylem embolism, narrower safety margins, and lower mortality rates during extreme droughts over 35years (1981-2015) among evergreen species. Species exposure to water stress declined with deeper ERD indicating that trees compensate for water stress-related mortality risk through deep-water access. The role of deep-water access in mitigating mortality of hydraulically-vulnerable trees has important implications for our predictive understanding of forest dynamics under current and future climates.

Normal-pressure hydrocephalus (NPH) is a common cause of gait apraxia, cognitive impairment, and urinary incontinence in the elderly. It is usually a primary idiopathic disorder but can be secondary. We present a case of secondary NPH due to biopsy-confirmed rheumatoid meningitis initially refractory to intravenous (IV) immunotherapy. Our patient reported an excellent response right after shunting. Her gait remains normal one and a half years later. We searched PubMed for similar cases of rheumatoid meningitis with gait abnormality for additional clinicopathologic discussion. The patient’s movement disorder initially improved with steroid taper. However, she developed progressive symptoms, later on, refractory to IV solumedrol and rituximab. She underwent ventriculoperitoneal shunting (VPS) and reported an outstanding outcome. This is the first reported biopsy-confirmed case of rheumatoid meningitis causing NPH to undergo shunting for immediate improvement. Previous cases of rheumatoid meningitis-associated Parkinsonism have improved with steroid induction. Although our patient’s rheumatoid arthritis is now controlled, her case illustrates that NPH in autoinflammatory conditions may not recover with immune suppression alone. VPS is an option for a faster response in secondary NPH due to rheumatoid meningitis or other inflammatory disorders with progressive symptoms despite standard induction therapy.

Vadose zone transport of tritium and nitrate can be important considerations at radioactive waste sites, landfills, or areas with industrial impacts. These contaminants are of particular concern because they typically have a relatively higher mobility in the subsurface compared to other compounds. Here, we describe a semiarid site with tritium and nitrate contamination involving a manmade ponded water source above a thick unsaturated zone at Los Alamos National Laboratory in New Mexico, USA. This study demonstrates the value of vadose zone flow and transport modeling for the development of field investigation plans (i.e., identifying optimal borehole locations and depths for contaminant characterization), and how a combination of modeling with isotope and geochemical measurements can provide insight into how tritium and nitrate transport in the vadose zone in semiarid environments. Modeling results suggest that at this location, tritium transport is well predicted by classical multiphase theory. Our work expands the demonstrated usefulness of a standard tritium conceptual model to sites with ponded surface conditions and agrees with previous results where a standard model was able to explain the evolution of a tritium plume at an arid waste disposal site. In addition, depth-based analyses of δ18O and δ2H of pore waters helped confirm the extent of pond infiltration into the vadose zone, and the δ15N of nitrate showed that the contaminant release history of the site was different than originally assumed.

Woodlands and pastures across the Post Oak Savannas (POS) in Texas have been undergoing thicketization over the last century via encroachment by understory shrubs such as Yaupon (Ilex decidua, Ilex vomitoria) and expansion of eastern redcedar (Juniperus virginiana). Because a large part of POS overlies the Carrizo-Wilcox (CW) aquifer - the third most important aquifer in Texas, there is a strong incentive to identify opportunities to increase groundwater recharge through land management. The purpose of this research is to evaluate the influence of thicketization of post oak (Quercus stellata) stands on deep drainage (DD) in POS. We achieved this by, a) applying chloride mass balance on soil cores, and b) simultaneously monitoring soil moisture in a woodland pasture setting in POS. Four sites representing different vegetation covers were identified for sampling: 1) a thicketized oak woodland paired with an adjacent open site, 2) a woodland mosaic, 3) a pasture and 4) a pine-oak stand paired with an adjacent open site. A total of 24 soil cores to the depth of 260 cm were collected and (soil) pore water chloride concentrations at multiple depths were measured. Soil moisture was monitored at 21 locations, to the depth of 140-260 cm using a neutron moisture meter. Negligible DD was estimated in the thicketized woodland, whereas most open locations recorded 3-18 cm/year and the woodland mosaic 0-1 cm of DD. Soil moisture data, collected from Jul-2020 to Jun-2021 also suggested higher deep drainage fluxes under open areas - with occurrence of sub-surface saturation only under the open areas and never under the woodlands. These results suggest that the thicketization in oak savannas is substantially reducing groundwater recharge. Given the extent of thicketized oak savannas across United States, this could be impacting water budgets and groundwater recharge rates on regional scales.

Background: While women have lower risks of cardiovascular disease (CVD) than men, type 2 diabetes mellitus (T2D) seems to be a stronger risk factor for major adverse cardiac events (MACE) for women. No study has evaluated sex differences in MACE for patients with T2D admitted for non-CVD diagnoses in the NIS. Pneumonia is one of the most common primary diagnoses in the inpatient setting. Methods: Patients hospitalized in 2013 for a primary diagnosis of pneumonia were identified from the NIS. MACE was defined as acute myocardial infarction (AMI) , ischemic stroke, cardiac arrest, or cardiogenic shock, and was compared by sex in patients with T2D. Multivariable logistic regression models were used to estimate odds of in-hospital MACE adjusted for demographics, cardiovascular risk factors, comorbidities, and pneumonia severity. Results: In 2013, 192,100 patients were admitted for a primary diagnosis of pneumonia, and 50,776 of these patients had T2D. Of the patients with T2D, 50.9% were female. Female patients with T2D were less likely to smoke and had fewer comorbidities than male patients with T2D (all P Conclusion: While T2D seems to be a stronger risk factor for AMI in female patients, male and female patients with T2D have an overall similar risk of in-hospital MACE when admitted for pneumonia. Disclosure S.Leventhal: None. G.Rubinfeld: None. J.S.Berger: Advisory Panel; Amgen Inc., Janssen Scientific Affairs, LLC. J.D.Newman: None. N.R.Smilowitz: Advisory Panel; Abbott.

Background: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. Aims: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. Methods: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers ( N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). Results: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. Conclusions: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.

Quorum sensing gene expression in vibrios is regulated by the LuxR/HapR family of transcriptional factors, which includes Vibrio vulnificus SmcR. The consensus binding site of Vibrio LuxR/HapR/SmcR proteins is palindromic but highly degenerate with sequence variations at each promoter. To examine the mechanism by which SmcR recognizes diverse DNA sites, we generated SmcR separation-of-function mutants that either repress or activate transcription but not both. SmcR N55I is restricted in recognition of single base-pair variations in DNA binding site sequences and thus is defective at transcription activation but retains interaction with RNA polymerase (RNAP) alpha. SmcR S76A, L139R and N142D substitutions disrupt the interaction with RNAP alpha but retain functional DNA binding activity. X-ray crystallography and small angle X-ray scattering data show that the SmcR DNA binding domain exists in two conformations (wide and narrow), and the protein complex forms a mixture of dimers and tetramers in solution. The three RNAP interaction-deficient variants also have two DNA binding domain conformations, whereas SmcR N55I exhibits only the wide conformation. These data support a model in which two mechanisms drive SmcR transcriptional activation: interaction with RNAP and a multi-conformational DNA binding domain that permits recognition of variable DNA sites.

Objective:Peripheral artery disease (PAD) is an atherothrombotic disease of the lower limbs with substantial morbidity and mortality. We used next-generation sequencing to identify genome-wide expression signatures associated with prevalent PAD and its outcomes.Approach and Results:We performed whole blood RNA sequencing among patients with severe symptomatic PAD undergoing lower extremity revascularization and controls. Dysregulated pathways and blood transcriptional modules were identified by comparing patients with PAD (n=42) to age- and sex-matched controls (N=29). The identified signature was compared in patients with PAD before LER with or without incident major adverse cardiac or limb events (MACLE). A novel microRNA associated with prevalent PAD and incident MACLE was then evaluated in a mouse hindlimb ischemia model. One hundred twenty-seven transcripts were differentially expressed (77 upregulated and 50 downregulated; adjustedP0.5) and analyzed using weighted gene co-expression network analysis. Weighted gene co-expression network analysis revealed blood modules enriched for immune activation, secretory granules, and coagulation in patients with PAD. Of these 127 differentially expressed transcripts, 40 were significantly associated with MACLE (log-rank false discovery rate Conclusions:A whole blood transcript signature identified patients with symptomatic PAD and PAD patients at increased risk of MACLE. A previously uncharacterized transcript microRNA-4477b was overexpressed in prevalent PAD, incident MACLE, and in a mouse hindlimb ischemia model. Our novel transcriptomic signature provides insight into potential mechanisms of patients with severe symptomatic PAD.

Refactoring is the art of improving the internal structure of a program without altering its external behavior, and it is an important task when it comes to software maintainability. While existing studies have focused on the detection of refactoring operations by mining software repositories, little was done to understand how developers document their refactoring activities. Therefore, there is recent trend trying to detect developers documentation of refactoring, by manually analyzing their internal and external software documentation. However, these techniques are limited by their manual process, which hinders their scalability. Hence, in this study, we tackle the detection of refactoring documentation as binary classification problem. We focus on the automatic detection of refactoring activities in commit messages by relying on text-mining, natural language preprocessing, and supervised machine learning techniques. We design our tool to overcome the limitation of the manual process, previously proposed by existing studies, through exploring the transformation of commit messages into features that are used to train various models. For our evaluation, we use and compare five different binary classification algorithms, and we test the effectiveness of these models using an existing dataset of manually curated messages that are known to be documenting refactoring activities in the source code. The experiments are carried out with different data sizes and number of bits. As per our results, the combination of Chi-Squared with Bayes point machine and Fisher score with Bayes point machine could be the most efficient when it comes to automatically identifying refactoring text patterns in commit messages, with an accuracy of 0.96, and an F-score of 0.96.

Tropical ecosystems contribute significantly to global emissions of methane (CH4), and landscape topography influences the rate of CH4 emissions from wet tropical forest soils. However, extreme events such as drought can alter normal topographic patterns of emissions. Here we explain the dynamics of CH4 emissions during normal and drought conditions across a catena in the Luquillo Experimental Forest, Puerto Rico. Valley soils served as the major source of CH4 emissions in a normal precipitation year (2016), but drought recovery in 2015 resulted in dramatic pulses in CH4 emissions from all topographic positions. Geochemical parameters including (i) dissolved organic carbon (C), acetate, and soil pH and (ii) hydrological parameters like soil moisture and oxygen (O2) concentrations varied across the catena. During the drought, soil moisture decreased in the slope and ridge, and O2 concentrations increased in the valley. We simulated the dynamics of CH4 emissions with the Microbial Model for Methane Dynamics-Dual Arrhenius and Michaelis–Menten (M3D-DAMM), which couples a microbial functional group CH4 model with a diffusivity module for solute and gas transport within soil microsites. Contrasting patterns of soil moisture, O2, acetate, and associated changes in soil pH with topography regulated simulated CH4 emissions, but emissions were also altered by rate-limited diffusion in soil microsites. Changes in simulated available substrate for CH4 production (acetate, CO2, and H2) and oxidation (O2 and CH4) increased the predicted biomass of methanotrophs during the drought event and methanogens during drought recovery, which in turn affected net emissions of CH4. A variance-based sensitivity analysis suggested that parameters related to aceticlastic methanogenesis and methanotrophy were most critical to simulate net CH4 emissions. This study enhanced the predictive capability for CH4 emissions associated with complex topography and drought in wet tropical forest soils.