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Abstract We describe an integrated modelling approach to accelerate the search for novel, single-phase, multicomponent materials with high magnetocrystalline anisotropy (MCA). For a given system we predict the nature of atomic ordering, its dependence on the magnetic state, and then proceed to describe the consequent MCA, magnetisation, and magnetic critical temperature (Curie temperature). Crucially, within our modelling framework, the same ab initio description of a material’s electronic structure determines all aspects. We demonstrate this holistic method by studying the effects of alloying additions in FeNi, examining systems with the general stoichiometries Fe4Ni3 X and Fe3Ni4 X, for additives including X = Pt, Pd, Al, and Co. The atomic ordering behaviour predicted on adding these elements, fundamental for determining a material’s MCA, is rich and varied. Equiatomic FeNi has been reported to require ferromagnetic order to establish the tetragonal L10 order suited for significant MCA. Our results show that when alloying additions are included in this material, annealing in an applied magnetic field and/or below a material’s Curie temperature may also promote tetragonal order, along with an appreciable effect on the predicted hard magnetic properties.

Weevils represent one of the most speciose and economically important animal clades, but remain poorly studied across much of the Oriental Region. Here, an integrative revision of the Oriental, flightless genus Aphanerostethus Voss, 1957 (Curculionidae: Molytinae) based on X-ray microtomography, multi-gene DNA barcoding (CO1, Cytb, 16S), and traditional morphological techniques (light microscopy, dissections) is presented. Twelve new species, namely, A. armatus Lewis & Kojima, sp. nov., A. bifidus Kojima & Lewis, sp. nov., A. darlingi Lewis, sp. nov., A. decoratus Lewis & Kojima, sp. nov., A. falcatus Kojima, Lewis & Fujisawa, sp. nov., A. incurvatus Kojima & Lewis, sp. nov., A. japonicus Lewis & Kojima, sp. nov., A. magnus Lewis & Kojima, sp. nov., A. morimotoi Kojima & Lewis, sp. nov., A. nudus Lewis & Kojima, sp. nov., A. spinosus Lewis & Kojima, sp. nov., and A. taiwanus Lewis, Fujisawa & Kojima, sp. nov. are described from Japan, Taiwan, Vietnam, and Malaysia. A neotype is designated for A. vannideki Voss, 1957. The hitherto monotypic genus Darumazo Morimoto & Miyakawa, 1985, syn. nov. is synonymized under Aphanerostethus based on new morphological data and Aphanerostethus distinctus (Morimoto & Miyakawa, 1985), comb. nov. is transferred accordingly. X-ray microtomography is successfully used to explore for stable interspecific differences in cuticular, internal and micro morphology. Remarkable species-specific sexual dimorphism in the metatibial uncus is described in seven of the newly described Aphanerostethus species and the evolution of this character is discussed.

Rationale Intense exercise promotes fatigue and can impair cognitive function, particularly toward the end of competition when decision-making is often critical for success. For this reason, athletes often ingest caffeinated energy drinks prior to or during exercise to help them maintain focus, reaction time, and cognitive function during competition. However, caffeine habituation and genetic sensitivity to caffeine (CA) limit efficacy. Paraxanthine (PX) is a metabolite of caffeine reported to possess nootropic properties. This study examined whether ingestion of PX with and without CA affects pre- or post-exercise cognitive function.Methods 12 trained runners were randomly assigned to consume in a double-blind, randomized, and crossover manner 400 mg of a placebo (PL); 200 mg of PL + 200 mg of CA; 200 mg of PL + 200 mg of PX (ENFINITY®, Ingenious Ingredients); or 200 mg PX + 200 mg of CA (PX+CA) with a 7–14-day washout between treatments. Participants donated fasting blood samples and completed pre-supplementation (PRE) side effects questionnaires, the Berg-Wisconsin Card Sorting Test (BCST), and the Psychomotor Vigilance Task Test (PVTT). Participants then ingested the assigned treatment and rested for 60 minutes, repeated tests (PRE-EX), performed a 10-km run on a treadmill at a competition pace, and then repeated tests (POST-EX). Data were analyzed using General Linear Model (GLM) univariate analyses with repeated measures and percent changes from baseline with 95% confidence intervals.Results BCST correct responses in the PX treatment increased from PRE-EX to POST-EX (6.8% [1.5, 12.1], p = 0.012). The error rate in the PL (23.5 [−2.8, 49.8] %, p = 0.078) and CA treatment (31.5 [5.2, 57.8] %, p = 0.02) increased from PRE-EX values with POST-EX errors tending to be lower with PX treatment compared to CA (−35.7 [−72.9, 1.4] %, p = 0.059). POST-EX perseverative errors with PAR rules were significantly lower with PX treatment than with CA (−26.9 [−50.5, −3.4] %, p = 0.026). Vigilance analysis revealed a significant interaction effect in Trial #2 mean reaction time values (p = 0.049, [Formula: see text] = 0.134, moderate to large effect) with POST-EX reaction times tending to be faster with PX and CA treatment. POST-EX mean reaction time of all trials with PX treatment was significantly faster than PL (−23.2 [−43.4, −2.4] %, p = 0.029) and PX+CA (−29.6 [−50.3, −8.80] %, p = 0.006) treatments. There was no evidence that PX ingestion adversely affected ratings of side effects associated with stimulant intake or clinical blood markers.Conclusions Results provide some evidence that pre-exercise PX ingestion improves prefrontal cortex function, attenuates attentional decline, mitigates cognitive fatigue, and improves reaction time and vigilance. Adding CA to PX did not provide additional benefits. Therefore, PX ingestion may serve as a nootropic alternative to CA.

ABSTRACT Iron-sulfur (Fe-S) clusters are ubiquitous inorganic cofactors required for numerous essential cellular pathways. Since they cannot be scavenged from the environment, Fe-S clusters are synthesized de novo in cellular compartments such as the apicoplast, mitochondrion, and cytosol. The cytosolic Fe-S cluster biosynthesis pathway relies on the transport of an intermediate from the mitochondrial pathway. An ATP-binding cassette (ABC) transporter called ABCB7 is responsible for this role in numerous commonly studied organisms, but its role in the medically important apicomplexan parasites has not yet been studied. Here we identify and characterize a Toxoplasma gondii ABCB7 homolog, which we name ABCB7-like (ABCB7L). Genetic depletion shows that it is essential for parasite growth and that its disruption triggers partial stage conversion. Characterization of the knock-down line highlights a defect in the biogenesis of cytosolic and nuclear Fe-S proteins leading to defects in protein translation and other pathways including DNA and RNA replication and metabolism. Our work provides support for a broad conservation of the connection between mitochondrial and cytosolic pathways in Fe-S cluster biosynthesis and reveals its importance for parasite survival.IMPORTANCEIron-sulfur (Fe-S) clusters are inorganic cofactors of proteins that play key roles in numerous essential biological processes, for example, respiration and DNA replication. Cells possess dedicated biosynthetic pathways to assemble Fe-S clusters, including a pathway in the mitochondrion and cytosol. A single transporter, called ABCB7, connects these two pathways, allowing an essential intermediate generated by the mitochondrial pathway to be used in the cytosolic pathway. Cytosolic and nuclear Fe-S proteins are dependent on the mitochondrial pathway, mediated by ABCB7, in numerous organisms studied to date. Here, we study the role of a homolog of ABCB7, which we name ABCB7-like (ABCB7L), in the ubiquitous unicellular apicomplexan parasite Toxoplasma gondii. We generated a depletion mutant of Toxoplasma ABCB7L and showed its importance for parasite fitness. Using comparative quantitative proteomic analysis and experimental validation of the mutants, we show that ABCB7L is required for cytosolic and nuclear, but not mitochondrial, Fe-S protein biogenesis. Our study supports the conservation of a protein homologous to ABCB7 and which has a similar function in apicomplexan parasites and provides insight into an understudied aspect of parasite metabolism.

Background: A growing evidence base supports the value of peer recovery support specialists (PRSS), particularly due to shared lived experience with participants (recipients of PRSS services). However, little research has examined whether congruence on certain aspects of “peerness” (e.g., demographics, experiences) matters for PRSS-participant relationships. Methods: Through a pilot study under the NIDA-funded Initiative for Justice and Emerging Adult Populations (JEAP), adults who had recently received PRSS services (N=100) were interviewed. Participants completed a modified version of the Scales for Participant Alliance with Recovery Coach (SPARC), a measure of PRSS-participant relationship quality, and rated themselves as different/similar to their PRSS in several domains using a six-point scale. Results: Participants had met with their PRSS for a median of 10 sessions over two months. SPARC scores were unrelated to participant demographics or lived experiences. However, better-quality relationships were reported by participants who believed their PRSS was similar to them in relationships with family (p=.004), spirituality/religion (p=.001), age (p

Abstract The mammalian target of rapamycin (mTOR), and specifically the mTOR complex 1 (mTORC1) is the central regulator of anabolism in skeletal muscle. Among the many functions of this kinase complex is the inhibition of the catabolic process of autophagy; however, less work has been done in investigating the role of autophagy in regulating mTORC1 signaling. Using an in vitro model to better understand the pathways involved, we activated mTORC1 by several different means (growth factors, leucine supplementation, or muscle contraction), alone or with the autophagy inhibitor NSC185058. We found that inhibiting autophagy with NSC185058 suppresses mTORC1 activity, preventing any increase in cellular protein anabolism. These decrements were the direct result of action on the mTORC1 kinase, which we demonstrate, for the first time, cannot function when autophagy is inhibited by NSC185058. Our results indicate that, far from being a matter of unidirectional action, the relationship between mTORC1 and the autophagic cascade is more nuanced, with autophagy serving as an mTORC1 input, and mTORC1 inhibition of autophagy as a form of homeostatic feedback to regulate anabolic signaling. Future studies of cellular metabolism will have to consider this fundamental intertwining of protein anabolism and catabolism, and how it ultimately serves to regulate muscle proteostasis.

Abstract Background Evidence indicating the optimal treatment protocol for dogs in adrenal crisis is lacking. Objectives Compare outcomes of dogs presented in adrenal crisis treated with either hydrocortisone (HC) continuous rate infusion (CRI) or intermittent dexamethasone (DEX) administration. Animals Thirty‐nine client‐owned dogs. Methods Multi‐institutional retrospective observational study (July 2016‐May 2022) including dogs diagnosed with adrenal crisis and with available sequential blood work during hospitalization. Dogs were excluded if already on treatment with exogenous corticosteroids. Outcomes assessed included duration of hospitalization, survival, number of repeat measurements of electrolyte concentrations, and time to normalization of electrolyte and acid‐base status. Results No significant difference was found between the groups for hospitalization time (P = .41; HC median [range] 48 h [19‐105 h]; DEX 57 h [17‐167 h]) nor case fatality rate 2/28 in the DEX group and 0/11 in the HC group (P = 1), nor in number of measurements of electrolyte concentrations (P = .90; HC 4 [2‐10]; DEX 4.5 [2‐15]). No significant differences were found between the 2 treatment groups in time to normalization of serum Na (P = .30; HC 33 h [7‐66 h]; DEX 16 h [1.5‐48 h]), K (P = .92; HC 17 h [4‐48 h]; DEX 16 h [1.25‐60 h]) or Na/K ratio (P = .08; HC 17 h [8‐48 h]; DEX 26 h [1.5‐60 h]). Conclusions This study detected no difference in outcomes for dogs in adrenal crisis treated with either DEX boluses or HC CRIs.

Abstract The aim of this study was to identify risk factors for abdominal aortic aneurysm (AAA) from the largest Welsh screening cohort to date. Patients were recruited from 1993 (to 2015) as part of the South East Wales AAA screening programme through general practitioners. Demographic data and risk factors were collected by means of a self‐report questionnaire. Statistical tests were performed to determine whether associations could be observed between AAA and potential risk factors. Odds ratios (OR) were also calculated for each of the risk factors identified. A total of 6879 patients were included in the study. Two hundred and seventy‐five patients (4.0%) presented with AAA, of which 16% were female and 84% were male. Patients with AAA were older than the (no AAA) control group (p

Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview.

Abstract Background Restricted repetitive behavior (RRB) is one of two behavioral domains required for the diagnosis of autism spectrum disorder (ASD). Neuroimaging is widely used to study brain alterations associated with ASD and the domain of social and communication deficits, but there has been less work regarding brain alterations linked to RRB. Methods We utilized neuroimaging data from the National Institute of Mental Health Data Archive to assess basal ganglia and cerebellum structure in a cohort of children and adolescents with ASD compared to typically developing (TD) controls. We evaluated regional gray matter volumes from T1-weighted anatomical scans and assessed diffusion-weighted scans to quantify white matter microstructure with free-water imaging. We also investigated the interaction of biological sex and ASD diagnosis on these measures, and their correlation with clinical scales of RRB. Results Individuals with ASD had significantly lower free-water corrected fractional anisotropy (FAT) and higher free-water (FW) in cortico-basal ganglia white matter tracts. These microstructural differences did not interact with biological sex. Moreover, both FAT and FW in basal ganglia white matter tracts significantly correlated with measures of RRB. In contrast, we found no significant difference in basal ganglia or cerebellar gray matter volumes. Limitations The basal ganglia and cerebellar regions in this study were selected due to their hypothesized relevance to RRB. Differences between ASD and TD individuals that may occur outside the basal ganglia and cerebellum, and their potential relationship to RRB, were not evaluated. Conclusions These new findings demonstrate that cortico-basal ganglia white matter microstructure is altered in ASD and linked to RRB. FW in cortico-basal ganglia and intra-basal ganglia white matter was more sensitive to group differences in ASD, whereas cortico-basal ganglia FAT was more closely linked to RRB. In contrast, basal ganglia and cerebellar volumes did not differ in ASD. There was no interaction between ASD diagnosis and sex-related differences in brain structure. Future diffusion imaging investigations in ASD may benefit from free-water estimation and correction in order to better understand how white matter is affected in ASD, and how such measures are linked to RRB.

Restricted repetitive behaviors (RRB) encompass a variety of inflexible behaviors, which are diagnostic for autism spectrum disorder (ASD). Despite being requisite diagnostic criteria, the neurocircuitry of these behaviors remains poorly understood, limiting treatment development. Studies in translational animal models show environmental enrichment (EE) reduces the expression of RRB, although the underlying mechanisms are largely unknown. This study used functional magnetic resonance imaging to identify functional connectivity alterations associated with RRB and its attenuation by EE in C58 mice, an animal model of RRB. Extensive differences were observed between C58 mice and C57BL/6 control mice. Higher RRB was associated with altered connectivity between the somatosensory network and reticular thalamic nucleus and between striatal and sensory processing regions. Animals housed in EE displayed increased connectivity between the somatosensory network and the anterior pretectal nucleus and hippocampus, as well as reduced connectivity between the visual network and area prostriata. These results suggest aberrant sensory perception is associated with RRB in C58 mice. EE may reduce RRB by altering functional connectivity in pain and visual networks. This study raises questions about the role of sensory processing and pain in RRB development and identifies new potential intervention targets.

Neutrinoless double beta decay is one of the most sensitive probes for new physics beyond the Standard Model of particle physics. One of the isotopes under investigation is ^{136}Xe, which would double beta decay into ^{136}Ba. Detecting the single ^{136}Ba daughter provides a sort of ultimate tool in the discrimination against backgrounds. Previous work demonstrated the ability to perform single atom imaging of Ba atoms in a single-vacancy site of a solid xenon matrix. In this paper, the effort to identify signal from individual barium atoms is extended to Ba atoms in a hexa-vacancy site in the matrix and is achieved despite increased photobleaching in this site. Abrupt fluorescence turn-off of a single Ba atom is also observed. Significant recovery of fluorescence signal lost through photobleaching is demonstrated upon annealing of Ba deposits in the Xe ice. Following annealing, it is observed that Ba atoms in the hexa-vacancy site exhibit antibleaching while Ba atoms in the tetra-vacancy site exhibit bleaching. This may be evidence for a matrix site transfer upon laser excitation. Our findings offer a path of continued research toward tagging of Ba daughters in all significant sites in solid xenon.

Abstract The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure‐induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom‐limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring ‘myth’ that AAA patients should be fearful of and avoid rigorous exercise. On the contrary, by appraising fundamental vascular mechanobiological forces associated with exercise, in conjunction with ‘methodological’ recommendations for risk mitigation specific to this patient population, we highlight that the benefits conferred by cardiopulmonary exercise testing and exercise training across the continuum of intensity far outweigh the short‐term risks posed by potential AAA rupture.

Snakebite envenoming is a priority Neglected Tropical Disease that causes an estimated 81,000–135,000 fatalities each year. The development of a new generation of safer, affordable, and accessible antivenom therapies is urgently needed. With this goal in mind, rigorous characterisation of the specific toxins in snake venom is key to generating novel therapies for snakebite. Monoclonal antibodies directed against venom toxins are emerging as potentially strong candidates in the development of new snakebite diagnostics and treatment. Venoms comprise many different toxins of which several are responsible for their pathological effects. Due to the large variability of venoms within and between species, formulations of combinations of human antibodies are proposed as the next generation antivenoms. Here a high-throughput screening method employing antibody-based ligand fishing of venom toxins in 384 filter-well plate format has been developed to determine the antibody target/s The approach uses Protein G beads for antibody capture followed by exposure to a full venom or purified toxins to bind their respective ligand toxin(s). This is followed by a washing/centrifugation step to remove non-binding toxins and an in-well tryptic digest. Finally, peptides from each well are analysed by nanoLC-MS/MS and subsequent Mascot database searching to identify the bound toxin/s for each antibody under investigation. The approach was successfully validated to rapidly screen antibodies sourced from hybridomas, derived from venom-immunised mice expressing either regular human antibodies or heavy-chain-only human antibodies (HCAbs).

Abstract Brown macroalgae habitats provide a range of ecosystem services, offering coastal protection, supporting and increasing biodiversity, and more recently have been recognized for their potential role as blue carbon habitats. Consequently, accurate areal estimates of these habitats are vitally important. Satellite imagery is often utilized for areal estimates of vegetated habitats due to their ability to capture vast areas but are disadvantaged by their lower resolution. In contrast, imagery collected by unmanned aerial vehicles (UAV) provide high‐resolution datasets but are unable to cover the necessary spatial scale required for calculating areal estimates at regional, national or international scales. This study successfully and accurately corrects the outputs from low‐resolution Sentinel 2 imagery to the standard of high‐resolution UAV imagery by using a novel brown algae index and a simple regression model to provide accurate spatial estimates. This model was applied to rocky shores across Wales, UK to predict a spatial extent of 6.2 km2 for three fucoid macroalgae species; Ascophyllum nodosum, Fucus vesiculosus and F. serratus. The regression model was validated in two ways. First, the data used to create the regression model was split to train and test (50:50) the model, with a root mean square error of ~8%–14%. Secondly, spatial estimates of fucoids in independent aerial imagery were assessed using aerial photography interpretation and compared to that of the regression model (7% difference). The carbon standing stock of fucoids calculated from the spatial estimate (6.2 km2) was found to be significantly lower than that of other marine carbon stores, indicating that fucoids do not significantly contribute as a blue carbon habitat based on biomass alone. This study produces a robust and accurate remote sensing technique to estimate spatial extent of macroalgae at large spatial scales, with possible worldwide applicability.

Abstract Streptococcus mutans is the primary oral caries-forming bacteria, adept at producing “sticky” biofilms via the synthesis of insoluble extracellular polysaccharides (EPS), catalyzed by glucosyltransferases (GTFs). To circumvent the use of broad-spectrum antibiotics to combat these bacteria, this study sought to modify existing EPS-targeting small molecules with the ultimate goal of producing anti-biofilm polymer surfaces specifically targeting S. mutans. To achieve this, a known GTF inhibitor (G43) was modified with methoxy or tetraethyleneglycol substitutions in different positions (nine derivatives, tested at 50-µM) to pinpoint potential sites for future methacrylate functionalization, and then assessed against single-species S. mutans biofilms. As expected, the compounds did not diminish the bacterial viability. In general, the compounds with methoxy substitution were not effective in reducing EPS formation, whereas the tetraethyleneglycol substitution (G43-C3-TEG) led to a decrease in the concentration of insoluble EPS, although the effect is less pronounced than for the parent G43. This aligns with the reduced GTF-C activity observed at different concentrations of G43-C3-TEG, as well as the consequent decrease in EPS formation, and notable structural changes. In summary, this study determined that G43-C3-TEG is non-bactericidal and can selectively reduce the biofilm formation, by decreasing the production of EPS. This molecule will serve to functionalize surfaces of materials to be tested in future research.

Abstract The production of locally atomically ordered FeNi (known by its meteoric mineral name, tetrataenite) is confirmed in bulk samples by simultaneous conversion X‐ray and backscattered γ‐ray 57Fe Mössbauer spectroscopy. Up to 22 volume percent of the tetragonal tetrataenite phase is quantified in samples thermally treated under simultaneous magnetic‐ and stress‐field conditions for a period of 6 weeks, with the remainder identified as the cubic FeNi alloy. In contrast, all precursor samples consist only of the cubic FeNi alloy. Data from the processed alloys are validated using Mössbauer parameters derived from natural meteoritic tetrataenite. The meteoritic tetrataenite exhibits a substantially higher degree of atomic order than do the processed samples, consistent with their low uniaxial magnetocrystalline anisotropy energy of ≈1 kJ·m−3. These results suggest that targeted refinements to the processing conditions of FeNi will foster greater atomic order and increased magnetocrystalline anisotropy, leading to an enhanced magnetic energy product. These outcomes also suggest that deductions concerning paleomagnetic conditions of the solar system, as derived from meteoritic data, may warrant re‐examination and re‐evaluation. Additionally, this work strengthens the argument that tetrataenite may indeed become a member of the advanced permanent magnet portfolio, helping to meet rapidly escalating green energy imperatives.

Background: Low-stress resin-based composites (RBCs) are available to the clinician, some using stress relaxation mechanisms on the basis of network reconfiguration, modulated photopolymerization, or chain transfer reactions. This study investigated those materials in terms of their overall stress relaxation and their relationship with polymerization kinetics and compared them with an experimental low-stress thiourethane (TU) material. Methods: Experimental composites (bisphenol-A-diglycidyl dimethacrylate, urethane dimethacrylate, and triethylene glycol dimethacrylate [50:30:20 mass ratio]; 70% barium aluminosilicate filler; camphoroquinone, ethyl-4-dimethylaminobenzoate, and 2,6-di-tert-butyl-4-methylphenol [0.2:0.8:0.2% by mass]) with or without TU oligomer (synthesized in-house) and commercial composites (SureFil SDR Flow+ Posterior Bulk Fill Flowable Base [SDR Flow+] [Dentsply Sirona], Filtek Bulk Fill Posterior Restorative [3M ESPE], and Filtek Supreme Ultra Universal Restorative [3M ESPE]) were tested. Polymerization kinetics (near-infrared) and polymerization stress (Bioman) were evaluated during light-emitting diode photoactivation at 100 mW/cm2 for 20 seconds. Stress relaxation was assessed using dynamic mechanical analysis. Data were analyzed with a 1-way analysis of variance and Tukey test (α = 0.05). Results: The kinetic profiles of all materials differed substantially, including more than a 2-fold difference in the rate of polymerization between TU-modified composites and SDR Flow+. TU-modified RBCs also showed more than a 2-fold higher conversion at the onset of deceleration vs the experimental control and commercial materials. RBCs that used stress reduction mechanisms showed at least a 34% reduction in polymerization stress compared with the controls and significantly reduced the amount of early-onset stress buildup. SDR Flow+ and the TU-modified RBCs showed the greatest amount of viscoelastic stress relaxation postpolymerization. Conclusions: The novel TU-modified materials showed similar or improved performance compared with commercial low-stress RBCs, showing that chain transfer may be a promising strategy for stress reduction, both during polymerization and after polymerization.

Abstract Objectives: Participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) has numerous benefits, yet many eligible children remain unenrolled. This qualitative study sought to explore perceptions of a novel electronic health record (EHR) intervention to facilitate referrals to WIC and improve communication/coordination between WIC staff and healthcare professionals. Methods: WIC staff in three counties were provided EHR access and recruited to participate. An automated, EHR-embedded WIC participation screening and referral tool was implemented within 8 healthcare clinics; healthcare professionals within these clinics were eligible to participate. The interview guide was developed using the Consolidated Framework for Implementation Research to elicit perceptions of this novel EHR-based intervention. Semi-structured interviews were conducted via telephone. Interviews were recorded, transcribed, coded, and analyzed using thematic analysis. Results: Twenty semi-structured interviews were conducted with eight WIC staff, seven pediatricians, four medical assistants, and one registered nurse. Most participants self-identified as female (95%) and White (55%). We identified four primary themes: (1) healthcare professionals had a positive view of WIC but communication and coordination between WIC and healthcare professionals was limited prior to WIC having EHR access; (2) healthcare professionals favored WIC screening using the EHR but workflow challenges existed; (3) EHR connections between WIC and the healthcare system can streamline referrals to and enrollment in WIC; and (4) WIC staff and healthcare professionals recommended that WIC have EHR access. Conclusions: A novel EHR-based intervention has potential to facilitate healthcare referrals to WIC and improve communication/coordination between WIC and healthcare systems.

Restricted, repetitive behaviors are common symptoms in neurodevelopmental disorders including autism spectrum disorder. Despite being associated with poor developmental outcomes, repetitive behaviors remain poorly understood and have limited treatment options. Environmental enrichment attenuates the development of repetitive behaviors, but the exact mechanisms remain obscure. Using the C58 mouse model of repetitive behavior, we performed diffusion tensor imaging to examine microstructural alterations associated with the development of repetitive behavior and its attenuation by environmental enrichment. The C57BL/6 mouse strain, which displays little or no repetitive behavior, was used as a control group. We observed widespread differences in diffusion metrics between C58 mice and C57BL/6 mice. In juvenile C58 mice, repetitive motor behavior displayed strong negative correlations with fractional anisotropy in multiple gray matter regions, whereas in young adult C58 mice, high repetitive motor behavior was most strongly associated with lower fractional anisotropy and higher radial diffusivity in the striatum. Environmental enrichment increased fractional anisotropy and axial diffusivity throughout gray matter regions in the brains of juvenile C58 mice and overlapped predominantly with cerebellar and sensory regions associated with repetitive behavior. Our results suggest environmental enrichment reduces repetitive behavior development by altering gray matter microstructure in the cerebellum, medial entorhinal cortex, and sensory processing regions in juvenile C58 mice. Under standard laboratory conditions, early pathology in these regions appears to contribute to later striatal and white matter dysfunction in adult C58 mice. Future studies should examine the role these regions play in the development of repetitive behavior and the relationship between sensory processing and cerebellar deficits and repetitive behavior.

Abstract Objectives: Evaluate system-wide antimicrobial stewardship program (ASP) update impact on intravenous (IV)-to-oral (PO) antimicrobial conversion in select community hospitals through pre- and postimplementation trend analysis. Methods: Retrospective study across seven hospitals: region one (four hospitals, 827 beds) with tele-ASP managed by infectious diseases (ID)-trained pharmacists and region two (three hospitals, 498 beds) without. Data were collected pre- (April 2022–September 2022) and postimplementation (April 2023–September 2023) on nine antimicrobials for the IV to PO days of therapy (DOTs). Antimicrobial administration route and (DOTs)/1,000 patient days were extracted from the electronical medical record (EMR). Primary outcome: reduction in IV DOTs/1,000 patient days. Secondary outcomes: decrease in IV usage via PO:total antimicrobial ratios and cost reduction. Results: In region one, IV usage decreased from 461 to 209/1,000 patient days (P = < .001), while PO usage increased from 289 to 412/1,000 patient days (P = < .001). Total antimicrobial use decreased from 750 to 621/1,000 patient days (P = < .001). In region two, IV usage decreased from 300 to 243/1,000 patient days (P = .005), and PO usage rose from 154 to 198/1,000 patient days (P = .031). The PO:total antimicrobial ratios increased in both regions, from .42–.52 to .60–.70 in region one and from .36–.55 to .46–.55 in region two. IV cost savings amounted to $19,359.77 in region one and $4,038.51 in region two. Conclusion: The ASP intervention improved IV-to-PO conversion rates in both regions, highlighting the contribution of ID-trained pharmacists in enhancing ASP initiatives in region one and suggesting tele-ASP expansion may be beneficial in resource-constrained settings.

Abstract Background Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin deficiency in patients with lipodystrophy – a group of rare diseases characterized by a paucity of adipose tissue. MEASuRE (Metreleptin Effectiveness And Safety Registry) is a post-authorization, voluntary registry that gathers long-term safety and effectiveness data on metreleptin. Here, we present the aims and evolution of MEASuRE. Methods MEASuRE was established to collect data from patients receiving commercially supplied metreleptin in the United States (US) and European Union (EU). MEASuRE aims to determine the incidence and severity of safety events and describe the clinical characteristics and therapeutic outcomes in the metreleptin-treated population. A key feature of MEASuRE is that it accumulates data from different sources to meet post-authorization objectives. US data are received directly from treating physicians via a contract research organization-mediated electronic data capture system. In the EU, data are received via the European Registry of Lipodystrophies managed by the European Consortium of Lipodystrophies (ECLip), a platform established by researchers and physicians to advance the knowledge of lipodystrophy. MEASuRE complies with applicable regulatory requirements governing privacy, and the storage, management, and access of data. Results Leveraging processes, infrastructure, and data from the ECLip registry presented several challenges that were addressed during MEASuRE’s development, including the expansion of the ECLip registry to accommodate MEASuRE-specific data elements, extensive data matching processes to ensure data consistency regardless of source, and rigorous data validation following the amalgamation of global data. Through the support of ECLip, MEASuRE is now a fully operational registry with the capacity for gathering and integrating standardized US- and EU-derived data. As of 31st October 2022, 15 US and four EU sites have participated in the MEASuRE, enrolling 85 patients globally. Conclusions Our experiences show that a post-authorization product registry can be successfully integrated into an existing patient registry. We propose that, through collaboration with existing registries and use of their established resources, patient enrolment timelines and data collection for new registries can be expedited. The learnings presented here may be applicable to other registries with similar objectives. Trial registration NCT02325674; Registered 25 December 2014 - Retrospectively registered’. https://clinicaltrials.gov/ct2/show/NCT02325674 .

In this paper we define RAL2 – the second Regional Atmosphere and Land (RAL) science configuration for regional modelling. RAL2 uses the Unified Model (UM) as the basis for the atmosphere and the Joint UK Land Environment Simulator (JULES) for the land. RAL2 defines the science configuration of the dynamics and physics schemes of the atmosphere and land and builds on the baseline of RAL1. There are two RAL2 sub-releases, one for mid-latitudes (RAL2-M) and one for tropical regions (RAL2-T). We document the differences between them and where appropriate discuss how RAL2 relates to RAL1 and the corresponding configuration of the global forecasting model. Our results show an increase in medium and low cloud amounts in the mid-latitudes leading to improved cloud forecasts. The increase in cloud amount leads to a reduced diurnal cycle of screen temperature. There is also a reduction in the frequency of heavier precipitation rates. RAL2 is expected to be the last RAL science configuration with two sub-releases as research effort is focused on producing a single defined configuration of the model that performs effectively in all regions of the world.

Abstract Background Uncontrolled hypertension is a leading risk factor for cardiovascular disease. To ensure continuity of care, community health centers (CHCs) nationwide implemented virtual care (telehealth) during the pandemic. CHCs use the Centers for Medicare & Medicaid Services (CMS) 165v8 Controlling High Blood Pressure measure to report blood pressure (BP) control performance. CMS 165v8 specifications state that if no BP is documented during the measurement period, the patient’s BP is assumed uncontrolled. Methods To examine trends in BP documentation and control rates in CHCs as telehealth use increased during the pandemic compared with pre-pandemic period, we assessed documentation of BP measurement and BP control rates from December 2019 - October 2021 among persons ages 18-85 with a diagnosis of hypertension who had an in-person or telehealth encounter in 11 CHCs. Rates were compared between CHCs that did and did not implement self-measured BP monitoring (SMBP). Results The percent of patients with hypertension with no documented BP measurement was 0.5% in December 2019 and increased to 15.2% (overall), 25.6% (non-SMBP CHCs), and 11.2% (SMBP CHCs) by October 2021. BP control using CMS 165v8 was 63.5% in December 2019 and decreased to 54.9% (overall), 49.1% (non-SMBP), and 57.2% (SMBP) by October 2021. When assessing BP control only in patients with documented BP measurements, CHCs largely maintained BP control rates (63.8% in December 2019; 64.8% (overall), 66.0% (non-SMBP), and 64.4% (SMBP) by October 2021). Conclusions The transition away from in-person to telehealth visits during the pandemic likely increased the number of patients with hypertension lacking a documented BP measurement, subsequently negatively impacting BP control using CMS 165v8. There is an urgent need to enhance the flexibility of virtual care, improve EHR data capture capabilities for patient-generated data, and implement expanded policy and systems-level changes for SMBP, an evidence-based strategy that can build patient trust, increase healthcare engagement, and improve hypertension outcomes.

Aim: To analyze the predictive value of biochemical liver tests in patients with malignant melanoma, breast, colorectal or lung cancers at the time of diagnosis of liver metastases. Methods: A retrospective review of patients with the above-mentioned solid tumors at MedStar Georgetown University Hospital from 2016–2020. Results: The highest optimal cutoff according to sensitivity and specificity for the presence of liver metastases was for AST ≥1.5 × ULN for melanoma, lung, and breast cancers and ≥2 × ULN for colorectal cancer, ALT ≥1.25 × ULN for melanoma, breast and colorectal cancers and ≥1.5 × ULN for lung cancer, and ALP ≥1.5 × ULN for melanoma, breast and colorectal cancers. Conclusion: Using thresholds of liver enzymes above the ULN may improve the diagnostic accuracy for the presence of liver metastases.

OBJECTIVES/GOALS: Research in Action is an on-demand, interactive curriculum designed to increase the ability of clinicians to advance the Academic Learning Health System (aLHS). The 7-module course provides clinicians with the knowledge and skills to lead rigorous quality improvement (QI) projects, translating research evidence into practice. METHODS/STUDY POPULATION: We engaged nurses, physicians, and advanced practice providers (APPs) working in the health system to participate in focus group and advise us in the creation of the curriculum. We conducted focus groups with these stakeholders on the proposed learning objectives, course content, and mode of delivery (in person, virtual, hybrid). Informed by the focus groups, the course was designed for hybrid format so participants could either (1) access the modules on-demand, or (2) learners could participate in a facilitator moderated course where the modules served as the curriculum to guide development of a QI project. The Iowa Model of Evidence-Based Practice was the framework for curriculum development. Upon completion of the modules, stakeholders reviewed each module and provided feedback for improvement. RESULTS/ANTICIPATED RESULTS: Research in Action is a 7-module course, with modules addressing the following topics: (1) Introduction to Quality Improvement, (2) Identify the Problem and Write a Purpose Statement, (3) Form a Team, (4) Appraise and Synthesize the Literature, (5) Design and Pilot the Project, (6) Integrate and Sustain Practice Change, (7) Disseminate the Results. The curriculum is being piloted with multiple clinician groups in the health system. In the next phase of development, a facilitator guide will be created to guide a cohort of clinicians to apply knowledge through discussion sessions and completion of a QI project in the healthcare setting. We anticipate scaling the program for spread to diverse clinician groups in the health system. Pre- and post-implementation data are being collected from current pilot sites. DISCUSSION/SIGNIFICANCE: The aLHS is an essential means for improving healthcare delivery. Research in Action, a hybrid training curriculum, engages frontline clinicians in creating and leading QI projects that implement research evidence into practice to solve problems commonly encountered in the healthcare setting; thus, supporting the advancement of the aLHS.

The rarely collected North American endemic genus Proctorus (Coleoptera, Curculionidae, Ellescini) has hitherto contained two described species, P. armatus LeConte, 1876 and P. decipiens (LeConte, 1876). Here, Proctorus is revised and two new species, namely P. emarginatus sp. nov. and P. truncatus sp. nov., are described. Lectotypes for P. armatus and P. decipiens are designated from known syntypes. All four species in the genus are associated with Salicaceae, but, in addition to differences in external and genital morphology, there is also evidence of differing host plant usage between the species. A photographic key to the four species is provided to facilitate identification.

Collection of finger sweat is explored here as a rapid and convenient way of monitoring patient adherence to antipsychotic drugs. Finger sweat samples (n = 426) collected from patients receiving treatment with clozapine, quetiapine and olanzapine were analysed by liquid chromatography mass spectrometry, including a subgroup of patients with paired plasma samples. Finger sweat samples were also analysed from a negative control group and patients who had handled antipsychotic medication only. The finger sweat test (based on the detection of parent drug in one donated sample) was 100% effective in monitoring adherence within commonly prescribed dosing ranges. In comparison to participants who handled the medication only, the test could distinguish between contact and administration through monitoring of the drug metabolite, or the level of parent drug. Additionally, in a subgroup of patients prescribed clozapine, a statistically significant correlation was observed between the mass of parent drug in finger sweat and plasma concentration. The finger sweat technology shows promise as a dignified, noninvasive method to monitor treatment adherence in patients taking antipsychotics.