Emergence of the isotropic Kitaev honeycomb latticeα-RuCl3and its magnetic properties.

We present a comprehensive investigation of the crystal and magnetic structures of the van der Waals antiferromagnetα-RuCl3using single crystal x-ray and neutron diffraction. The crystal structure at room temperature is a monoclinic (C2/m). However, with decreasing temperature, a remarkable first-order structural phase transition is observed, leading to the emergence of a rhombohedral (R3-) structure characterized by three-fold rotational symmetry forming an isotropic honeycomb lattice. On further cooling, a zigzag-type antiferromagnetic order develops belowTN=6∼6.6K. The critical exponent of the magnetic order parameter was determined to beß=0.11(1), which is close to the two-dimensional Ising model. Additionally, the angular dependence of the magnetic critical field of the zigzag antiferromagnetic order for the polarized ferromagnetic phase reveals a six-fold rotational symmetry within theab-plane. These findingsreflect the symmetry associated with the Ising-like bond-dependent Kitaev spin interactions and underscore the universality of the Kitaev interaction-dominated antiferromagnetic system.

Virtual surgical planning for mandibular reconstruction in an abbreviated admission pathway.

OBJECTIVES: Virtual Surgical Planning (VSP) creates individualized surgical plans for free flap reconstruction of mandibular defects. Prior studies indicate that VSP can offer cost benefits due to reduced operative time and length of stay (LOS). We assessed the impact of VSP in the context of a validated postoperative abbreviated LOS clinical pathway. METHODS: This study assessed patients undergoing VSP vs conventional fibular free flap reconstruction for mandibular defects (12/2015-10/2020) and their operative time, ischemia time, and LOS were evaluated. RESULTS: Forty-four patients underwent VSP reconstruction, while 52 patients underwent conventional reconstruction for mandibular defects. VSP was associated with significantly lower total operative time (6 h and 57 mins vs 7 h and 54 mins, p = 0.011), but not length of stay or ischemia time. Total OR time was significantly increased with increasing number of segments needed in both the VSP group (p = 0.002) and the conventional group (p = 0.015). CONCLUSION: Shorter operative times and LOS have been attributed to the use of VSP in free tissue transfers. It is argued that these reductions offset the added cost of VSP. Our study indicates that there is no cost benefit for VSP utilization due to a significantly reduced operative time with no impact on length of admission in an abbreviated admission clinical pathway following free tissue transfer.

Microvascular Free Flap Outcomes in Maxillectomy Defects from Invasive Fungal Sinusitis.

OBJECTIVES: Microvascular free tissue transfer is routinely used for reconstructing midface defects in patients with malignancy, however, studies regarding reconstructive outcomes in invasive fungal sinusitis (IFS) are lacking. We aim to describe outcomes of free flap reconstruction for IFS defects, determine the optimal time to perform reconstruction, and if anti-fungal medications or other risk factors of an immunocompromised patient population affect reconstructive outcomes. METHODS: Retrospective review of reconstruction for IFS (2010-2022). Age, BMI, hemoglobin A1c, number of surgical debridements, and interval from the last debridement to reconstruction were compared between patients with delayed wound healing versus those without. Predictor variables for delayed wound healing and the effect of time on free flap reconstruction were analyzed. RESULTS: Twenty-seven patients underwent free flap reconstruction for IFS. Three patients were immunocompromised from leukemia and 21 had diabetes mellitus (DM). Patients underwent an average of four surgical debridements for treatment of IFS. The interval from the last IFS debridement to flap reconstruction was 5.58 months (±5.5). Seven flaps (25.9%) had delayed wound healing. A shorter interval of less than 2 months between the last debridement for IFS and reconstructive free flap procedure was associated with delayed wound healing (Fisher Exact Test p = 0.0062). Other factors including DM, BMI, HgA1c, and bone reconstruction were not associated with delayed wound healing. CONCLUSION: Patients with maxillectomy defects from IFS can undergo microvascular-free flap reconstruction with good outcomes while on anti-fungal medication. Early reconstruction in the first 2 months after the last IFS debridement is associated with delayed wound healing. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1642-1647, 2024.

MAIP: An Open-Source Tool to Enrich High-Throughput Screening Output and Identify Novel, Druglike Molecules with Antimalarial Activity.

Efforts to tackle malaria must continue for a disease that threatens half of the global population. Parasite resistance to current therapies requires new chemotypes that are able to demonstrate effectiveness and safety. Previously, we developed a machine-learning-based approach to predict compound antimalarial activity, which was trained on the compound collections of several organizations. The resulting prediction platform, MAIP, was made freely available to the scientific community and offers a solution to prioritize molecules of interest in virtual screening and hit-to-lead optimization. Here, we experimentally validate MAIP and demonstrate how the approach was used in combination with a robust compound selection workflow and a recently introduced innovative high-throughput screening (HTS) cascade to select and purchase compounds from a public library for subsequent experimental screening. We observed a 12-fold enrichment compared with a randomly selected set of molecules, and the eight hits we ultimately selected exhibit good potency and absorption, distribution, metabolism, and excretion (ADME) profiles.

Design of the Global Health chemical diversity library v2 for screening against infectious diseases.

There is a need for novel chemical matter for phenotypic and target-based screens to find starting points for drug discovery programmes in neglected infectious diseases and non-hormonal contraceptives that disproportionately affect Low- and Middle-Income Countries (LMICs). In some disease areas multiple screens of corporate and other libraries have been carried out, giving rise to some valuable starting points and leading to preclinical candidates. Whilst in other disease areas, little screening has been carried out. Much screening against pathogens has been conducted phenotypically as there are few robustly validated protein targets. However, many of the active compound series identified share the same molecular targets. To address the need for new chemical material, in this article we describe the design of a new library, designed for screening in drug discovery programmes for neglected infectious diseases. The compounds have been selected from the Enamine REAL (REadily AccessibLe) library, a virtual library which contains approximately 4.5 billion molecules. The molecules theoretically can be synthesized quickly using commercially available intermediates and building blocks. The vast majority of these have not been prepared before, so this is a source of novel compounds. In this paper we describe the design of a diverse library of 30,000 compounds from this collection (graphical abstract). The new library will be made available to laboratories working in neglected infectious diseases, subject to a review process. The project has been supported by the Bill & Melinda Gates Foundation and the Wellcome Trust (Wellcome).

The increasing threat to European forests from the invasive foliar pine pathogen, Lecanosticta acicola.

European forests are threatened by increasing numbers of invasive pests and pathogens. Over the past century, Lecanosticta acicola, a foliar pathogen predominantly of Pinus spp., has expanded its range globally, and is increasing in impact. Lecanosticta acicola causes brown spot needle blight, resulting in premature defoliation, reduced growth, and mortality in some hosts. Originating from southern regions of North American, it devastated forests in the USA's southern states in the early twentieth century, and in 1942 was discovered in Spain. Derived from Euphresco project 'Brownspotrisk,' this study aimed to establish the current distribution of Lecanosticta species, and assess the risks of L. acicola to European forests. Pathogen reports from the literature, and new/ unpublished survey data were combined into an open-access geo-database (http://www.portalofforestpathology.com), and used to visualise the pathogen's range, infer its climatic tolerance, and update its host range. Lecanosticta species have now been recorded in 44 countries, mostly in the northern hemisphere. The type species, L. acicola, has increased its range in recent years, and is present in 24 out of the 26 European countries where data were available. Other species of Lecanosticta are largely restricted to Mexico and Central America, and recently Colombia. The geo-database records demonstrate that L. acicola tolerates a wide range of climates across the northern hemisphere, and indicate its potential to colonise Pinus spp. forests across large swathes of the Europe. Preliminary analyses suggest L. acicola could affect 62% of global Pinus species area by the end of this century, under climate change predictions. Although its host range appears slightly narrower than the similar Dothistroma species, Lecanosticta species were recorded on 70 host taxa, mostly Pinus spp., but including, Cedrus and Picea spp. Twenty-three, including species of critical ecological, environmental and economic significance in Europe, are highly susceptible to L. acicola, suffering heavy defoliation and sometimes mortality. Variation in apparent susceptibility between reports could reflect variation between regions in the hosts' genetic make-up, but could also reflect the significant variation in L. acicola populations and lineages found across Europe. This study served to highlight significant gaps in our understanding of the pathogen's behaviour. Lecanosticta acicola has recently been downgraded from an A1 quarantine pest to a regulated non quarantine pathogen, and is now widely distributed across Europe. With a need to consider disease management, this study also explored global BSNB strategies, and used Case Studies to summarise the tactics employed to date in Europe.

Outcomes After Pharyngeal Flap Surgery in Children: A Comparison of Lined Versus Unlined Flaps.

OBJECTIVE: The addition of a uvular flap (PFU) was hypothesized to improve outcomes over standard pharyngeal flap (PF) for correction of velopharyngeal dysfunction. We report differences in outcomes of PF vs PFU at our institution. DESIGN: Retrospective cohort study. SETTING: Tertiary children's hospital. PATIENTS: Children who underwent PF or PFU with the three highest-volume surgeons at our institution in 2004-2017. OUTCOME MEASURES: We examined differences in complications between groups, frequency and type of revision surgery, and speech-related measures including nasometry, pressure-flow testing (PFT) and perceptual speech analysis (PSA). RESULTS: 160 patients were included, 41 PF and 119 PFU (including 18 with Hogan technique). Patients undergoing PFU were older (7.6 yr vs 6.0 yr; p = 0.037) and more likely to have cleft palate (63/119 vs 14/41; p = 0.047). There was no significant difference in complications. With PFU, a decrease in airspace contracting revision surgeries was noted, (4/119 vs 8/41; p = 0.002) which drove a reduction in revision surgery of all types (7/119 vs 13/41; p = 0.033). However, patients that did undergo revision surgery after PFU underwent more revision procedures (p = 0.032). PSA scores were found to be lower (less hypernasal) after PFU (p = 0.009) compared to PF. Objective speech measures had varying results, with nasometry demonstrating a significant difference between groups (p = 0.001), while PFT (p = 0.525) did not demonstrate a statistical difference. CONCLUSION: The use of a uvular lining flap in pharyngeal flap surgery may be associated with improved long term surgical outcomes, including both improvements in subjective and objective testing and a lower rate of revision surgery, without increased complications.

An evaluation of the Chesapeake Bay management strategy to improve water quality in small agricultural watersheds.

Chesapeake Bay water quality has been a concern since 1970. In rural areas, agriculture is the dominant N and P source, and the voluntary application of best management practices (BMPs) is the primary management tool. Here we test the hypothesis that the current management approach of primarily voluntary, untargeted BMP implementation is insufficient to create detectable, widespread reductions in N, P, and total suspended solid (TSS) concentrations in agricultural watersheds of the Choptank basin, a tributary of Chesapeake Bay. To test this hypothesis, we assessed BMP implementation and sampled water quality on participating farms, at intermediate streams within each watershed, and at watershed outlets of four watersheds from 2013 to 2014. We also present water quality data from 2003 to 2014 at the outlets of 12 additional agricultural and one forested watershed and survey-directed interviews of farmers. By the end of 2014, large numbers of BMPs, both structural and cultural, had been implemented. Of the 16 agricultural watersheds, 50% showed significant decreases in baseflow N, 37.5% showed no changes, and 12.5% showed increasing TN. Baseflow P significantly decreased at just one watershed, increased at one, and remained stable at 14. Stormflow N was similar to baseflow, but stormflow P was 5 times higher than baseflow. These data partially support our hypothesis. Surveys suggested farmers considered themselves responsible for the quality of water leaving their farms, but out-of-pocket cost was the major impediment to further BMP adoption. We suggest that greater outreach and more financial support for farmers to implement BMPs is required to increase the types and densities of BMPs needed to achieve regional water quality goals.

The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species.

Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg.

Utilizing process improvement strategies to generate clinic templates and improve patient flow in pediatric otolaryngology.

OBJECTIVES: To examine outcomes from process improvement strategies aimed to: 1) develop computer generated physician clinic templates using captured and historic clinical data, and, 2) introduce said new template designs while maintaining historic daily patient volumes. METHODS: An Institutional Review Board approved retrospective review of time stamped data collection in a tertiary facility pediatric otolaryngology clinic. RESULTS: A discrete-event simulation was built from timestamps associated with clinic interaction milestones. The data were analyzed to develop standard clinic templates with the goal to reduce patient overall visit length by 10%. A total of 12,052 clinic visits were analyzed, 8,045 before (avg. of 62.9 visits/day) and 4,007 after (avg. of 65.7 visits/day) template standardization. The change led to a 10.5% (5.5 min, p < 0.001) decrease in total clinic visit time from 52.3 ± 25.9 min to 46.8 ± 25.0 min. This data extrapolated over a year is estimated to save 1,567 clinic hours. Secondarily, it was found that patient experience was not affected as a result of this change. CONCLUSION: Discrete-event simulation, using the principles of process improvement, is effective in guiding clinic operational redesign. This quality improvement project decreased the average length of clinic visit by 10% with no impact on historic high clinic volumes. Patient flow can improve in high volume pediatric otolaryngology practices by using process improvement strategies and discrete-event simulations to create standardized provider templates. Theoretically, this strategy can lead to improved patient and physician experiences along with an increase in patient visits over time.

Propranolol for Treatment of Infantile Hemangioma: Efficacy and Effect on Pediatric Growth and Development.

PURPOSE: Propranolol has been successful in treating problematic infantile hemangiomas (IH) but concerns regarding its effect on normal growth and development have been raised. This study examines physical growth, developmental milestones, and human growth hormone (hGH) levels in infants receiving propranolol for problematic IH. METHOD: Monthly heights and weights of children undergoing propranolol therapy for IH were prospectively collected and tabulated. Data analysis and comparison to World Health Organization (WHO) weight-for-age and weight-to-length z-scores was performed. Questionnaires regarding milestones, efficacy, and guardian satisfaction were performed, and a combination of both chart results and phone conducted surveys was tabulated. Serum from a small representative cohort of age-matched children with IH treated and not treated with propranolol was collected. RESULTS: A total of 185 children receiving propranolol therapy between 2008 and 2013 for IH were assigned to this study. The children were divided into two cohorts based on the presence of comorbidities or risk factors that may affect growth and development (n = 142 no comorbidities, n = 43 with comorbidities). Neither cohort demonstrated deviation from normal weight in comparison to WHO normative data. There was a significant deviation for BMI-for-age and weight-for-age z-scores in our population, especially in patients on propranolol for more than 7 months. Based on data from participants, via either completed questionnaires or chart results, most children met their developmental milestones at or before target ages, regardless of the presence of comorbidities. Eighty percent of guardians noticed clinical improvement of the IH, with 91% either happy about or neutral to using the medication. hGH levels were higher in patients receiving propranolol therapy, but not significantly different. CONCLUSION: Propranolol therapy is effective and well tolerated in the treatment of infantile hemangiomas. This study suggests that propranolol does not impair growth and has no impact on normal pediatric development.

Process improvement strategy to implement an outpatient surgery center efficiency model in an academic inpatient setting.

OBJECTIVES: By utilizing process improvement methodology, we aim to: 1) create an ambulatory surgical efficiency model (SEM) confined to an inpatient setting, and 2) reduce patient wait time and improve patient flow within the operating room. METHODS: A prospective cohort of all otolaryngology cases performed from May 2016 to October 2017 at a tertiary, academic, pediatric hospital. Intraoperative timestamps were collected to determine turnover times. Time to procedure was collected from clinic visit to the day of operation. RESULTS: A total of 5955 patients were enrolled. 3393 cases were performed prior to the implementation of SEM and 2562 after. Of the 2562 cases, 819 were deemed appropriate for the SEM. Prior to the SEM, the average number of working days between the clinic visit and operating room (WD) was 31.1 days (95% CI 30.7-31.4). After the SEM, the WD for non-SEM cases was 30.0 days (95% CI 29.7-30.2), and the WD for SEM cases was 14.4 days (95% CI 14.2-14.6). The average turnover time was significantly less for SEM cases at 11.4 min (95% CI 10.7-12.2) vs. non-SEM cases at 24.4 min (95% CI 23.9-25.0) (p < 0.0001). CONCLUSION: Process improvement methodology is effective in improving perioperative patient flow. This quality improvement project decreased the average time from diagnosis to surgical procedure, as well as decreased the average turnover time between cases. Patient flow can improve with a high-volume SEM within an inpatient hospital operating room setting. This strategy can be instrumental in improving patient care by providing increased access to the operating room.

Clinical Significance of Screening Electrocardiograms for the Administration of Propranolol for Problematic Infantile Hemangiomas.

OBJECTIVE: Low-dose nonselective ß blockade is an effective treatment for problematic infantile hemangioma (PIH). Screening electrocardiograms (ECG) are performed prior to the initiation of propranolol to minimize the risk of exacerbating undiagnosed heart block. How ECG results affect subsequent propranolol usage and patient management remains unclear. We examined the value of ECG prior to propranolol therapy in a quaternary pediatric hospital. METHODS: A retrospective chart review was performed on all infants who received propranolol (2 mg/kg/day divided three times daily) to treat PIH at Arkansas Children's Hospital from Sept. 2008 to Sept. 2015. All available demographic, historical, and clinical data were obtained. ECGs and echocardiographic data were reviewed and summarized. A pediatric cardiologist read all ECGs. RESULTS: A total of 333 patients (75% female) received propranolol therapy. ECG information was available for 317 (95%). Abnormal findings were present on 44/317 (13.9%) of study ECGs. The most common abnormal finding was "voltage criteria for ventricular hypertrophy" (n = 35, 76.1%). Two patients had abnormal rhythms; one had first-degree atrioventricular (AV) block, and one had occasional premature atrial contractions. Of the 31 patients who underwent echocardiograms, 20 (35%) were abnormal. 2.9% of infants with PIH treated with propranolol required a follow-up with a cardiologist. No patient was precluded from taking propranolol due to the findings on screening ECG. CONCLUSIONS: Screening ECGs prior to propranolol therapy are abnormal in nearly 14% of patients with PIH but are unlikely to preclude therapy. In the absence of prior cardiac history, this cohort offers further evidence suggesting that screening ECGs may be of limited value in determining the safety of propranolol in otherwise healthy infants with PIH.

MAIP: a web service for predicting blood-stage malaria inhibitors.

Malaria is a disease affecting hundreds of millions of people across the world, mainly in developing countries and especially in sub-Saharan Africa. It is the cause of hundreds of thousands of deaths each year and there is an ever-present need to identify and develop effective new therapies to tackle the disease and overcome increasing drug resistance. Here, we extend a previous study in which a number of partners collaborated to develop a consensus in silico model that can be used to identify novel molecules that may have antimalarial properties. The performance of machine learning methods generally improves with the number of data points available for training. One practical challenge in building large training sets is that the data are often proprietary and cannot be straightforwardly integrated. Here, this was addressed by sharing QSAR models, each built on a private data set. We describe the development of an open-source software platform for creating such models, a comprehensive evaluation of methods to create a single consensus model and a web platform called MAIP available at https://www.ebi.ac.uk/chembl/maip/ . MAIP is freely available for the wider community to make large-scale predictions of potential malaria inhibiting compounds. This project also highlights some of the practical challenges in reproducing published computational methods and the opportunities that open-source software can offer to the community.

Operative and postoperative outcomes in elderly patients undergoing endoscopic sinus surgery.

PURPOSE: Chronic rhinosinusitis (CRS) is increasingly common in the elderly population (≥ 65 years old). Compared to their younger counterparts, differences exist in the etiology of CRS and outcomes of Endoscopic Sinus Surgery (ESS) for elderly patients. The aim of this study is to determine if differences in surgical outcomes are present between these two patient populations to facilitate patient pre-operative counseling by their healthcare providers. METHODS: Retrospective chart review conducted at a single tertiary care center for patients undergoing ESS between June 2014 and June 2019. Patients were classified into two cohorts (adult and elderly) based on age (< 65 and ≥ 65 years old). Demographics, surgical, and postoperative variables were extracted from our institution's electronic medical records. ANOVA and t-test analysis were performed to determine the presence of significant differences between the two cohorts. SNOT-22 scores were used to determine QOL improvements. RESULTS: Compared to the adult cohort, elderly patients had significant QOL improvement after surgical treatment (p = 0.001), but had a similar successful response to treatment (p = 0.74). Elderly patients had no difference in the incidence of operative/perioperative complications (p = 0.89) or intraoperative or postoperative bleeding (p = 0.301, p = 0.62), but had an increased incidence of postoperative infection (p = 0.000). CONCLUSION: ESS remains an effective treatment modality for the management of CRS, and a safe practice for elderly patients despite the increase in complexity of their medical comorbidities and polypharmacy. QOL improvements are significant, though patient counseling should take into account that improvements may not be as pronounced as in younger patients.

Effects of motion and audio-visual redundancy on upright and inverted face and feature preferences in 4-13-month old pre- and full-term NICU graduates.

NICU infants are reported to have diminished social orientation and increased risk of socio-communicative disorders. In this eye tracking study, we used a preference for upright compared to inverted faces as a gauge of social interest in high medical risk full- and pre-term NICU infants. We examined the effects of facial motion and audio-visual redundancy on face and eye/mouth preferences across the first year. Upright and inverted baby faces were simultaneously presented in a paired-preference paradigm with motion and synchronized vocalization varied. NICU risk factors including birth weight, sex, and degree of CNS injury were examined. Overall, infants preferred the more socially salient upright faces, making this the first report, to our knowledge, of an upright compared to inverted face preference among high medical risk NICU infants. Infants with abnormalities on cranial ultrasound displayed lower social interest, i.e. less of a preferential interest in upright faces, when viewing static faces. However, motion selectively increased their upright face looking time to a level equal that of infants in other CNS injury groups. We also observed an age-related sex effect suggesting higher risk in NICU males. Females increased their attention to the mouth in upright faces across the first year, especially between 7-10 months, but males did not. Although vocalization increased diffuse attention toward the screen, contrary to our predictions, there was no evidence that the audio-visual redundancy embodied in a vocalizing face focused additional attention on upright faces or mouths. This unexpected result may suggest a vulnerability in response to talking faces among NICU infants that could potentially affect later verbal and socio-communicative development.

Listeria monocytogenes Response to Anaerobic Environments.

Listeria monocytogenes is a Gram-positive facultative anaerobic bacterium that is responsible for the disease, listeriosis. It is particularly lethal in pregnant women, the fetus, the elderly and the immunocompromised. The pathogen survives and replicates over a wide range of temperatures (4 to 42 °C), pH, salt and oxygen concentrations. Because it can withstand various environments, L. monocytogenes is a major concern in food processing industries, especially in dairy products and ready-to-eat fruits, vegetables and deli meats. The environment in which the pathogen is exposed can influence the expression of virulence genes. For instance, studies have shown that variations in oxygen availability can impact resistance to stressors. Further investigation is needed to understand the essential genes required for the growth of L. monocytogenes in anaerobic conditions. Therefore, the purpose of this review is to highlight the data on L. monocytogenes under known environmental stresses in anaerobic environments and to focus on gaps in knowledge that may be advantageous to study in order to better understand the pathogenicity of the bacterium.

Inflammatory cardiac fibroblast phenotype underlies chronic alcohol-induced cardiac atrophy and dysfunction.

AIMS: The purpose of this study was to investigate mechanisms of chronic alcohol-induced cardiac remodeling and dysfunction. We also sought to determine the role of cardiac fibroblasts, which play a dynamic role in cardiac remodeling, in mediating these effects. MAIN METHODS: Adult male Wistar rats were exposed to ethanol (EtOH) vapor inhalation for 16 weeks. Echocardiography was performed to assess terminal cardiac structure and function. Cardiac fibroblasts were isolated from the left ventricle (LV) for both ex vivo and in vitro analysis. Cultured H9C2 cells were also exposed to conditioned media from alcohol-exposed cardiac fibroblasts. Gene expression in whole LV tissue, isolated cardiac fibroblasts, or cultured H9C2 cells was determined by real-time PCR, and protein expression was determined by Western blot. KEY FINDINGS: EtOH led to LV wall thinning and impaired systolic function, and decreased contractile protein mRNA levels. EtOH increased LV inflammatory markers, JNK and Akt activation, and decreased mTOR expression. EtOH induced myofibroblast activation as assessed by flow cytometry, and increased LV collagen III expression. EtOH increased expression of several inflammatory mediators in cardiac fibroblasts both ex vivo and in vitro. Administration of conditioned media from EtOH-treated fibroblasts decreased contractile protein mRNA levels and impaired Akt and mTOR signaling in differentiated H9C2 cardiomyocytes. SIGNIFICANCE: Our results indicate that EtOH-induced cardiac atrophy and dysfunction is associated with activation of inflammatory pathways. Furthermore, EtOH may induce a pro-inflammatory cardiac fibroblast phenotype, leading to aberrant fibroblast-myocyte cross-talk. Thus, EtOH may promote cardiac muscle wasting in part by activation of pro-inflammatory fibroblasts.

Tin titanate-the hunt for a new ferroelectric perovskite.

We review all the published literature and show that there is no experimental evidence for homogeneous tin titanate SnTiO3 in bulk or thin-film form. Instead a combination of unrelated artefacts are easily misinterpreted. The x-ray Bragg data are contaminated by double scattering from the Si substrate, giving a strong line at the 2θ angle exactly where perovskite SnTiO3 should appear. The strong dielectric divergence near 560 K is irreversible and arises from oxygen site detrapping, accompanied by Warburg/Randles interfacial anomalies. The small (4 µC cm-2) apparent ferroelectric hysteresis remains in samples shown to be pure (Sn,Ti)O2 rutile/cassiterite, in which ferroelectricity is forbidden. Only very recent work reveals real bulk SnTiO3, but it possesses an ilmenite-like structure with an elaborate array of stacking faults, not suitable for ferroelectric devices. Unpublished TEM data reveal an inhomogeneous SnO layered structured thin films, related to shell-core structures. The harsh conclusion is that there is a combination of unrelated artefacts masquerading as ferroelectricity in powders and ALD films; and only a trace of a second phase in PLD film data suggests any perovskite content at all. The fact that x-ray, dielectric, and hysteresis data all lead to the wrong conclusion is instructive and reminds us of earlier work on copper calcium titanate (a well-known boundary-layer capacitor).

Characterization of a high-brightness, laser-cooled Li+ ion source.

Ion sources based on laser cooling have recently provided new pathways to high-resolution microscopy, ion milling, and ion implantation. Here, we present the design and detailed characterization of a 7Li magneto-optical trap ion source (MOTIS) with a peak brightness of (1.2 ± 0.2) × 105 A m-2 sr-1 eV-1 and a maximum continuous current over 1 nA. These values significantly surpass previous Li MOTIS performance benchmarks. Using simple models, we discuss how the performance of this system relates to fundamental operating limits. This source will support a range of projects using lithium ion beams for surface microscopy and nanostructure characterization, including Li+ implantation for studies of ionic transport in energy storage materials.