A randomized clinical trial to evaluate feasibility, tolerability, and preliminary target engagement for a novel executive working memory training in adolescents with ADHD.

OBJECTIVE: Working memory training for Attention-Deficit/Hyperactivity Disorder (ADHD) has focused on increasing working memory capacity, with inconclusive evidence for its effectiveness. Alternative training targets are executive working memory (EWM) processes that promote flexibility or bolster stability of working memory contents to guide behavior via selective attention. This randomized, placebo-controlled study was designed to assess feasibility, tolerability, and behavioral target engagement of a novel EWM training for ADHD. METHOD: 62 ADHD-diagnosed adolescents (12-18 years) were randomized to EWM training or placebo arms for 20 remotely coached sessions conducted over 4-5 weeks. Primary outcome measures were behavioral changes on EWM tasks. Secondary outcomes were intervention tolerability, trial retention, and responsiveness to adaptive training difficulty manipulations. RESULTS: Linear regression analyses found intervention participants showed medium effect size improvements, many of which were statistically significant, on Shifting and Filtering EWM task accuracy and Shifting and Updating reaction time measures. Intervention participants maintained strong self-rated motivation, mood, and engagement and progressed through the adaptive difficulty measures, which was further reflected in high trial retention. CONCLUSIONS: The results suggest that these EWM processes show promise as training targets for ADHD. The subsequent NIMH R33-funded extension clinical trial will seek to replicate and extend these findings.

Martian atmospheric hydrogen and deuterium: Seasonal changes and paradigm for escape to space.

Mars' water history is fundamental to understanding Earth-like planet evolution. Water escapes to space as atoms, and hydrogen atoms escape faster than deuterium giving an increase in the residual D/H ratio. The present ratio reflects the total water Mars has lost. Observations with the Mars Atmosphere and Volatile Evolution (MAVEN) and Hubble Space Telescope (HST) spacecraft provide atomic densities and escape rates for H and D. Large increases near perihelion observed each martian year are consistent with a strong upwelling of water vapor. Short-term changes require processes in addition to thermal escape, likely from atmospheric dynamics and superthermal atoms. Including escape from hot atoms, both H and D escape rapidly, and the escape fluxes are limited by resupply from the lower atmosphere. In this paradigm for the escape of water, the D/H ratio of the escaping atoms and the enhancement in water are determined by upwelling water vapor and atmospheric dynamics rather than by the specific details of atomic escape.

A Mock Circulatory Loop Analysis of Cardiorenal Hemodynamics With Intra-Aortic Mechanical Circulatory Support.

Type 1 cardiorenal syndrome is associated with significant excess morbidity and mortality in patients with severe acute decompensated heart failure. Previous trials of vasoactive drugs and ultrafiltration have not shown superiority over placebo or intravenous diuretics. Pilot data suggest short-term mechanical support devices may support diuresis in the cardiorenal syndrome. We evaluated the intra-aortic balloon pump (IABP) and a novel intra-aortic entrainment pump (IAEP) in a mock circulation loop (MCL) biventricular systolic heart failure model, to assess impact on renal flow and cardiac hemodynamics. Both devices produced similar and only modest increase in renal flow (IABP 3.3% vs. IAEP 4.3%) and cardiac output, with associated reduction in afterload elastance in the MCL. There were minor changes in coronary flow, increase with IABP and minor decrease with IAEP. Differences in device preload and afterload did not impact percentage change in renal flow with IABP therapy, however, there was a trend toward higher percentage flow change with IAEP in response to high baseline renal flow. The IAEP performed best in a smaller aorta and with more superior positioning within the descending aorta. Demonstrated changes in MCL flow during IAEP were of lower magnitude than previous animal studies, possibly due to lack of autoregulation and hormonal responses.

Differentiation, adaptation, and perseverance: Maturing conceptualizations of education-focused science faculty in the United States.

Science education reform has been underway for almost a century with the general aim to engage students and train scientists needed to find solutions to global challenges, and also ensure a general public well disposed towards science. In an effort to aid science reform, more recently, colleges and universities have been augmenting their academic workforce by embedding education-focused science faculty into science departments. However, little research has investigated how this approach, and the identity of these faculty, may be changing over time. Here we investigate how conceptualizations of professional identities of these faculty across the United States have changed over the last two decades. We found three professional identities amongst these faculty: Science Faculty with Education Specialties (SFES), Discipline-Based Education Researchers (DBER), and faculty who identify as both SFES and DBER. Evidence indicates this is a maturing field within higher-education science departments, with more direct hiring and training pathways, but with potentially diminishing agency. Finally, data reveal resilience and perseverance despite negative biases from peers and college administrators, especially at PhD-granting institutions.

An exploration of neural predictors of treatment compliance in cognitive-behavioral group therapy for hoarding disorder.

A persistent and influential barrier to effective cognitive-behavioral therapy (CBT) for patients with hoarding disorder (HD) is treatment retention and compliance. Recent research has suggested that HD patients have abnormal brain activity identified by functional magnetic resonance (fMRI) in regions often engaged for executive functioning (e.g., right superior frontal gyrus, anterior insula, and anterior cingulate), which raises questions about whether these abnormalities could relate to patients' ability to attend, understand, and engage in HD treatment. We examined data from 74 HD-diagnosed adults who completed fMRI-measured brain activity during a discarding task designed to elicit symptom-related brain dysfunction, exploring which regions' activity might predict treatment compliance variables, including treatment engagement (within-session compliance), homework completion (between-session compliance), and treatment attendance. Brain activity that was significantly related to within- and between-session compliance was found largely in insula, parietal, and premotor areas. No brain regions were associated with treatment attendance. The results add to findings from prior research that have found prefrontal, cingulate, and insula activity abnormalities in HD by suggesting that some aspects of HD brain dysfunction might play a role in preventing the engagement needed for therapeutic benefit.

Integrating Computational and Biological Hemodynamic Approaches to Improve Modeling of Atherosclerotic Arteries.

Atherosclerosis is the primary cause of cardiovascular disease, resulting in mortality, elevated healthcare costs, diminished productivity, and reduced quality of life for individuals and their communities. This is exacerbated by the limited understanding of its underlying causes and limitations in current therapeutic interventions, highlighting the need for sophisticated models of atherosclerosis. This review critically evaluates the computational and biological models of atherosclerosis, focusing on the study of hemodynamics in atherosclerotic coronary arteries. Computational models account for the geometrical complexities and hemodynamics of the blood vessels and stenoses, but they fail to capture the complex biological processes involved in atherosclerosis. Different in vitro and in vivo biological models can capture aspects of the biological complexity of healthy and stenosed vessels, but rarely mimic the human anatomy and physiological hemodynamics, and require significantly more time, cost, and resources. Therefore, emerging strategies are examined that integrate computational and biological models, and the potential of advances in imaging, biofabrication, and machine learning is explored in developing more effective models of atherosclerosis.

Horizontal versus vertical strategies for infection prevention: current practices and controversies.

PURPOSE OF REVIEW: Healthcare-associated infections (HAIs) represent a major burden on healthcare facilities. Effective infection prevention strategies are essential to prevent the spread of HAIs. These can be broadly classified as vertical and horizontal interventions. Through this review, we aim to assess the merits of these strategies. RECENT FINDINGS: Vertical strategies include active surveillance testing and isolation for patients infected or colonized with a particular organism. These strategies are beneficial to curb the spread of emerging pathogens and during outbreaks. However, the routine use of contact precautions for organisms such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus remains controversial. Horizontal interventions are larger-scale and reduce HAIs by targeting a common mode of transmission shared by multiple organisms. Among these, hand hygiene, chlorhexidine gluconate bathing of select patients and environmental decontamination are the most high-yield and must be incorporated into infection prevention programs. As antimicrobial stewardship is also an effective horizontal strategy, antimicrobial stewardship programs must operate in synergy with infection prevention programs for maximal impact. SUMMARY: Overall, horizontal interventions are considered more cost-effective and have a broader impact. Infection control programs may opt for a combination of vertical and horizontal strategies based on local epidemiology and available resources.

Occupational exposures to asbestos in the steel industry: An analysis of the AISI sampling campaign (1989-1997).

The American Iron and Steel Institute (AISI) gathered data between 1989 and 1997 to build an "objective database" to further understand the occupational exposures generated by the few asbestos-containing materials remaining at various steelmaking companies at this time. This paper analyzed the 520 samples from this campaign which occurred at five different steel manufacturers: Georgetown Steel Company, Inland Steel Company, Ling-Temco-Vought (LTV) Corporation, United States Steel Corporation, and Weirton Steel Corporation. This database is believed to have never previously been systematically organized. Samples were grouped based on sampling times to determine whether they should most appropriately be compared to the OSHA short-term excursion limit (EL) or the 8-hr time-weighted average (TWA) permissible exposure limit (PEL). Sampling times of 30 min or less were considered short-term samples, and samples of 180 min or greater were considered representative workday samples. Samples that did not fit into either category, with sampling times between 31 and 179 min, were considered task samples. Overall, the data indicated that the airborne concentrations were quite low in 1989 and they continued to be low through the study period which ended in 1997. Only seven out of 286 (approximately 2.5%) short-term or representative workday samples were in exceedance of the current OSHA OELs that were implemented in 1994 (short-term samples being compared to the 1 f/cc EL and representative workday samples being compared to the 0.1 f/cc 8-hr TWA PEL). Consistent with prior data, analysis of this dataset supports the view that materials containing asbestos were not used in many applications in the steel industry, and measured airborne concentrations of asbestos were almost always below the occupational exposure limits (OELs) in the post-OSHA era (1972-2000).

The presence of erionite in North American geologies and the estimated mesothelioma potency by region.

OBJECTIVE: Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers. MATERIALS AND METHODS: Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined. RESULTS AND DISCUSSION: The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5. CONCLUSION: The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent).

Design and high-throughput implementation of MALDI-TOF/MS-based assays for Parkin E3 ligase activity.

Parkinson's disease (PD) is a progressive neurological disorder that manifests clinically as alterations in movement as well as multiple non-motor symptoms including but not limited to cognitive and autonomic abnormalities. Loss-of-function mutations in the gene encoding the ubiquitin E3 ligase Parkin are causal for familial and juvenile PD. Among several therapeutic approaches being explored to treat or improve the prognosis of patients with PD, the use of small molecules able to reinstate or boost Parkin activity represents a potential pharmacological treatment strategy. A major barrier is the lack of high-throughput platforms for the robust and accurate quantification of Parkin activity in vitro. Here, we present two different and complementary Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF/MS)-based approaches for the quantification of Parkin E3 ligase activity in vitro. Both approaches are scalable for high-throughput primary screening to facilitate the identification of Parkin modulators.

The natural and human-mediated expansion of a human-commensal lizard into the fringes of Southeast Asia.

BACKGROUND: Human-commensal species often display deep ancestral genetic structure within their native range and founder-effects and/or evidence of multiple introductions and admixture in newly established areas. We investigated the phylogeography of Eutropis multifasciata, an abundant human-commensal scincid lizard that occurs across Southeast Asia, to determine the extent of its native range and to assess the sources and signatures of human introduction outside of the native range. We sequenced over 350 samples of E. multifasciata for the mitochondrial ND2 gene and reanalyzed a previous RADseq population genetic dataset in a phylogenetic framework. RESULTS: Nuclear and mitochondrial trees are concordant and show that E. multifasciata has retained high levels of genetic structure across Southeast Asia despite being frequently moved by humans. Lineage boundaries in the native range roughly correspond to several major biogeographic barriers, including Wallace's Line and the Isthmus of Kra. Islands at the outer fringe of the range show evidence of founder-effects and multiple introductions. CONCLUSIONS: Most of enormous range of E. multifasciata across Southeast Asia is native and it only displays signs of human-introduction or recent expansion along the eastern and northern fringe of its range. There were at least three events of human-introductions to Taiwan and offshore islands, and several oceanic islands in eastern Indonesia show a similar pattern. In Myanmar and Hainan, there is a founder-effect consistent with post-warming expansion after the last glacial maxima or human introduction.

Contact precautions as a barrier to hand hygiene: The Plan-Do-Study-Act (PDSA) framework to improve compliance with gloved hand hygiene.

In an identified quality improvement effort, nurses were observed regarding their workflow while in contact precaution rooms. Multiple opportunities for hand hygiene were missed while nurses were in gloves, predominantly while moving between "dirty" and "clean" tasks. An education initiative afterward did not show improvement in hand hygiene rates.

Estradiol effects on an emotional interference task in adolescents with current and remitted depression.

Attentional biases to emotional stimuli are thought to reflect vulnerability for mood disorder onset and maintenance. This study examined the association between the endogenous sex hormone estradiol and emotional attentional biases in adolescent females with either current or remitted depression. Three groups of participants (mean age ± SD) completed the Emotional Interrupt Task: 1) 20 adolescent females (15.1 ± 1.83 years) currently diagnosed with Major Depressive Disorder (MDD), 2) 16 adolescent females (16.4 ± 1.31 years) who had experienced at least one episode of MDD in their lifetime but currently met criteria for MDD in remission, and 3) 30 adolescent female (15.4 ± 1.83 years) healthy controls. Attentional interference (AI) scores were calculated as differences in target response reaction time between trials with emotional facial expressions versus neutral facial expressions. Estradiol levels were assayed by Salimetrics LLC using saliva samples collected within 30 min of waking on assessment days. Robust multiple regression with product terms evaluated estradiol's main effect on AI scores, as well as hypothesized estradiol × diagnostic group interactions. Although neither mean estradiol levels nor mean AI scores in the current-MDD and remitted-MDD groups differed from controls, the relationship between estradiol and overall AI score differed between control adolescents and the remitted-MDD group. Specifically, the remitted-MDD adolescents performed worse (i.e., showed greater attentional interference) when they had higher estradiol; no significant relationship existed in the current-MDD group. Because this finding was driven by angry and not happy stimuli, it appears higher estradiol levels were associated with greater susceptibility to the attention-capturing effects of negatively-valenced emotional content in girls at risk for MDD from prior history.

Diblock bottlebrush polymer in a non-polar medium: Self-assembly, surface forces, and superlubricity.

Whilst bottlebrush polymers have been studied in aqueous media for their conjectured role in biolubrication, surface forces and friction mediated by bottlebrush polymers in non-polar media have not been previously reported. Here, small-angle neutron scattering (SANS) showed that a diblock bottlebrush copolymer (oligoethyleneglycol acrylate/ethylhexyl acrylate; OEGA/EHA) formed spherical core-shell aggregates in n-dodecane (a model oil) in the polymer concentration range 0.1-2.0 wt%, with a radius of gyration Rg âˆ¼ 7 nm, comprising 40-65 polymer molecules per aggregate. The surface force apparatus (SFA) measurements revealed purely repulsive forces between surfaces bearing inhomogeneous polymer layers of thickness L âˆ¼ 13-23 nm, attributed to adsorption of a mixture of polymer chains and surface-deformed micelles. Despite the surface inhomogeneity, the polymer layers could mediate effective lubrication, demonstrating superlubricity with the friction coefficient as low as µ ∼ 0.003. The analysis of velocity-dependence of friction using the Eyring model shed light on the mechanism of the frictional process. That is, the friction mediation was consistent with the presence of nanoscopic surface aggregates, with possible contributions from a gel-like network formed by the polymer chains on the surface. These unprecedented results, correlating self-assembled polymer micelle structure with the surface forces and friction the polymer layers mediate, highlight the potential of polymers with the diblock bottlebrush architecture widespread in biological living systems, in tailoring desired surface interactions in non-polar media.

Coated Cast Saw Blades Decrease Blade Temperature During Cast Removal.

BACKGROUND: Thermal injuries can occur during cast removal with an oscillating saw. The purpose of this study is to describe the effect of blade material, blade wear, and cast material on blade temperature. METHODS: Short arm plaster and fiberglass casts were cured overnight and bivalved with either new or worn stainless-steel or tungsten-disulfide coated blades. Blade use was defined as removing 1 short arm cast. Blades used to remove more than 20 casts were defined as worn. Ten trials were performed with each combination of blade material, blade wear, and cast material, except for the combination of fiberglass and a worn stainless-steel blade due to complete erosion of cutting teeth. Thirty casts were removed with stainless-steel blades, and 40 casts were removed with coated blades. Blade temperature was measured continuously at 5 Hz using a T-type thermocouple and microcontroller board. A Mann-Whitney U test was used to compare the mean maximum temperature between groups. RESULTS: For plaster casts, new and worn stainless-steel blades produced mean maximum temperatures of 51.4°C and 63.7°C ( P =0.003), respectively. New stainless-steel blades produced significantly higher mean maximum temperatures on fiberglass casts than plaster casts (95.9°C vs. 51.4°C, P <.001). For plaster casts, new and worn coated blades produced mean maximum temperatures of 56.9°C and 53.8°C ( P =0.347). For fiberglass casts, new and worn coated blades produced mean maximum temperatures of 76.6°C and 77.7°C ( P =0.653). As with new stainless-steel blades, new coated blades produced significantly higher mean maximum temperatures on fiberglass than plaster (76.6°C vs. 56.9°C, P <0.001). Mean maximum temperatures between new stainless-steel and coated blades during removal of plaster casts were 51.4°C and 56.9°C ( P =0.131), respectively. However, new coated blades demonstrated significantly lower mean maximum temperatures during fiberglass cast removal compared to new stainless-steel blades (76.6°C vs. 95.9°C, P =0.016). CONCLUSIONS: Coated blades outperformed stainless-steel in nearly all combinations. We recommend limited use of stainless-steel blades to minimize blade temperatures during cast removal. CLINICAL RELEVANCE: Appropriate selection of blade material and monitoring blade wear minimizes blade temperature during cast removal.

A one-pot reduction route to bimetallic manganese 1,8-naphthyridine complexes.

Reaction of the dinucleating ligand 2,7-bis(6-methyl-2-pyridyl)-1,8-naphthyridine (MeL) with the MnI and MnII precursors MnBr(CO)5 and MnCl2 resulted in the formation of the monometallic complexes [MnBr(CO)3(MeL)] (1) and [MnCl2(MeL)] (3). In both cases, formation of bimetallic manganese complexes could be achieved by reduction with KC8, yielding the carbonyl-bridged complex [Mn2(CO)6(MeL)] (2) and the helicate complex [Mn2(MeL)2] (4), respectively. EPR results demonstrate that 4 represents a novel, weakly antiferromagnetically coupled homovalent dimer (J = -0.85 cm-1). The two formally Mn0 ions are both high spin (S = 3/2) and exhibit a zero-field splitting of ≈1 cm-1, suggesting reduction of the complex is substantially ligand centered, and may be better described as a MnII complex coupled to two open shell singlet ligands [MnII2(MeL2-)2]. X-ray crystallography, UV-Vis spectroscopy and DFT analysis support this finding.

Evaluating Indices for Non-invasive Myocardial Recovery Assessment in LVAD-Supported Heart Failure Patients.

Accurate assessment of myocardial recovery (MR) under left ventricular assist device (LVAD) support is essential for clinicians to manage heart failure patients. However, current techniques for assessing MR are time-consuming, invasive, and infrequent. Measuring MR using indices derived from LVAD operating data instead provides a potential real-time alternative. Several of these indices for assessing the MR of LVAD-supported heart failure patients were collated from the literature and subject to a comprehensive comparative analysis. The objective of this analysis was to determine the most accurate index for assessing systolic cardiac function under LVAD-support, characterized by maximal end-systolic elastance (Emax), while remaining insensitive to preload & afterload. The indices were compared in computational simulation, utilizing an LVAD + cardiovascular system model to sweep through a large array of Emax and resistance conditions. Results demonstrated the index that correlated best with Emax, showing the highest accuracy, was the ratio between maximum flow acceleration and flow pulsatility (average R2 =0.9790). The same index also exhibited the lowest % variation (sensitivity) to preload & afterload (1.32% & 13.53% respectively). However, opportunities for improvement remain among current recovery assessment indices, with this study providing a baseline of performance for potential future indices to improve upon.Clinical relevance- This study presents a potential real-time measure of native cardiac function in LVAD-supported heart failure patients to support patient management and further recovery.

The use of UV-C radiation for terminal disinfection of pathogenic Gram-negative rods: a pilot study.

In this controlled study, we found that exposure to ultraviolet-C (UV-C) radiation was able to arrest the growth of selected pathogenic enteric and nonfermenting Gram-negative rods. Further studies are needed to confirm the clinical efficacy and determine optimal implementation strategies for utilizing UV-C terminal disinfection.

Three-Dimensional Energy Transfer in Space Plasma Turbulence from Multipoint Measurement.

A novel multispacecraft technique applied to Magnetospheric Multiscale Mission data in the Earth's magnetosheath enables evaluation of the energy cascade rate from the full Yaglom's equation. The method differs from existing approaches in that it (i) is inherently three-dimensional, (ii) provides a statistically significant number of estimates from a single data stream, and (iii) allows visualization of energy flux in turbulent plasmas. This new "lag polyhedral derivative ensemble" technique exploits ensembles of tetrahedra in lag space and established curlometerlike algorithms.