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Abstract Ultrafast manipulation of the Néel vector in metallic antiferromagnets most commonly occurs by generation of spin-orbit (SOT) or spin-transfer (STT) torques. Here, we predict another possibility for antiferromagnetic domain switching by using novel laser optical torques (LOTs). We present results of atomistic spin dynamics simulations from the application of LOTs for all-optical switching of the Néel vector in the antiferromagnet Mn2Au. The driving mechanism takes advantage of the sizeable exchange enhancement, characteristic of antiferromagnetic dynamics, allowing for picosecond 90 and 180-degree precessional toggle switching of the Néel vector with laser fluences on the order of mJ/cm2. A special symmetry of these novel torques greatly minimises the over-shooting effect common to precessional spin switching by SOT and STT methods. We demonstrate the opportunity for LOTs to produce deterministic, non-toggle switching of single antiferromagnetic domains. Lastly, we show that even with sizeable ultrafast heating by laser in metallic systems, there exist a large interval of laser parameters where the LOT-assisted toggle and preferential switchings in magnetic grains have probabilities close to one. The proposed protocol could be used on its own for all-optical control of antiferromagnets for computing or memory storage, or in combination with other switching methods to lower energy barriers and/or to prevent over-shooting of the Néel vector.

Abstract Coherent light-matter interactions mediated by opto-magnetic phenomena like the inverse Faraday effect (IFE) are expected to provide a non-thermal pathway for ultrafast manipulation of magnetism on timescales as short as the excitation pulse itself. As the IFE scales with the spin-orbit coupling strength of the involved electronic states, photo-exciting the strongly spin-orbit coupled core-level electrons in magnetic materials appears as an appealing method to transiently generate large opto-magnetic moments. Here, we investigate this scenario in a ferrimagnetic GdFeCo alloy by using intense and circularly polarized pulses of extreme ultraviolet radiation. Our results reveal ultrafast and strong helicity-dependent magnetic effects which are in line with the characteristic fingerprints of an IFE, corroborated by ab initio opto-magnetic IFE theory and atomistic spin dynamics simulations.

Abstract Adiponectin (APN) is an adipokine which predominantly expresses in adipocytes with neuroprotective and anti-inflammatory effects. We have recently indicated that circulatory trimeric APN can enter the brain by crossing the blood–brain barrier (BBB) and modulate microglia-mediated neuroinflammation. Here, we found that the microglial NLR family pyrin domain containing 3 (NLRP3)-inflammasome activation was exacerbated in APN −/− 5xFAD mice in age-dependent manner. The focus of this study was to develop a new and tractable therapeutic approach for treating Alzheimer’s disease (AD)-related pathology in 5xFAD mice using peripheral APN gene therapy. We have generated and transduced adeno-associated virus (AAV2/8) expressing the mouse mutated APN gene (APNC39S) into the liver of 5xFAD mice that generated only low-molecular-weight trimeric APN (APNTri). Single dose of AAV2/8-APNC39S in the liver increased circulatory and cerebral APN levels indicating the overexpressed APNTri was able to cross the BBB. Overexpression of APNTri decreased both the soluble and fibrillar Aβ in the brains of 5xFAD mice. AAV2/8-APNTri treatment reduced Aβ-induced IL-1β and IL-18 secretion by suppressing microglial NLRP3-inflammasome activation. The memory functions improved significantly in AAV-APNTri-treated 5xFAD mice with reduction of dystrophic neurites. These findings demonstrate that peripheral gene delivery to overexpress trimeric APN can be a potential therapy for AD. Graphical Abstract

In mammals, the molecular mechanisms underlying transgenerational inheritance of phenotypic traits in serial generations of progeny after ancestral environmental exposures, without variation in DNA sequence, remain elusive. We’ve recently described transmission of a beneficial trait in rats and mice, in which F0 supplementation of methyl donors, including folic acid, generates enhanced axon regeneration after sharp spinal cord injury in untreated F1 to F3 progeny linked to differential DNA methylation levels in spinal cord tissue. To test whether the transgenerational effect of folic acid is transmitted via the germline, we performed whole-genome methylation sequencing on sperm DNA from F0 mice treated with either folic acid or vehicle control, and their F1, F2, and F3 untreated progeny. Transgenerational differentially methylated regions (DMRs) are observed in each consecutive generation and distinguish folic acid from untreated lineages, predominate outside of CpG islands and in regions of the genome that regulate gene expression, including promoters, and overlap at both the differentially methylated position (DMP) and gene levels. These findings indicate that molecular changes between generations are caused by ancestral folate supplementation. In addition, 29,719 DMPs exhibit serial increases or decreases in DNA methylation levels in successive generations of untreated offspring, correlating with a serial increase in the phenotype across generations, consistent with a ‘wash-in’ effect. Sibship-specific DMPs annotate to genes that participate in axon- and synapse-related pathways.

Background: At a comprehensive cancer center, hundreds of patients are screened daily for infections requiring the implementation of isolation precautions. Discontinuation of precautions is determined by negative testing, resolution of infection, or other criteria. Determining appropriate discontinuation of isolation precautions is labor intensive for Infection Preventionists (IPs). An unintended consequence of manual discontinuation is that numerous patients remain on isolation indefinitely. This was amplified during the COVID-19 pandemic when thousands of patients were placed on isolation precautions. Using electronic health record (EHR) tools, opportunities for process improvements were developed. Our goal was to establish an automated method to resolve isolation precautions. We aimed to decrease the number of manually resolved precautions by 25% each fiscal year (FY), compared to our baseline of activity in FY 2019 (FY19). Our secondary aim was to automate adding and resolving precautions when testing is initiated for suspected transmissible conditions (rule-out testing features).

Background: Candida auris (C. auris) is a multidrug-resistant fungus that is increasingly implicated in outbreaks in healthcare facilities worldwide. The Centers for Disease Control and Prevention (CDC) and the Texas Department of State Health Services recommend healthcare facilities screen patients who are considered high-risk for C. auris, including patients with an overnight stay in a healthcare facility outside the United States (U.S.) in the previous year, or recently stayed in a rehabilitation (rehab) facility, long-term acute care (LTAC), or skilled nursing facility (SNF). Screening patients for C. auris colonization allows for early implementation of infection control measures, preventing transmission to healthcare workers and other patients. According to the CDC, most cases of C. auris result from local spread within and among healthcare facilities in the same city or state. In Texas, 160 clinical cases have been reported during the past 12 months. At present, the necessity of screening high-risk patients at our center for C. auris is not known. We aimed to determine the prevalence of C. auris colonization among our patient population. Method: During a 4-week period, we performed targeted screening of patients meeting the CDC’s high-risk definition for C. auris. Admitted patients were screened by an Infection Preventionist (IP) using the electronic health record to identify patients who were either international or admitted from a rehab or care facility. A composite swab of bilateral axilla and groin creases was collected using an eSwab™ (Becton Dickinson) and sent to a reference lab (Mayo Clinic Laboratories) for polymerase chain reaction (PCR)-based detection of C. auris. Additionally, we reviewed historic cases of C. auris diagnosed at our institution to better define our at-risk patients. Results: Between July 14 – August 8, 2023, we consecutively screened 25 high-risk patients, including 18 (72%) international and 7 (28%) patients from rehabs, LTAC, or SNF. None were positive for C. auris. Since 2019, we identified six patients with C. auris positive cultures, including five clinical cases and one colonization case. Five patients were international and one was local with no history of international travel or stay in a care facility. Interestingly, all six were known to be colonized with extended-spectrum beta-lactamase (ESBL) E. coli. Conclusion: We have a very low prevalence of C. auris among CDC-defined high-risk patients. A review of historic C. auris cases indicated an association with colonization by other multidrug-resistant organisms, specifically ESBL E. coli, which will inform future screening protocols at our institution.

Background: Healthcare-acquired infections (HAIs) continue to be a major challenge. In fact, an increased risk of HAIs has been linked to high-touch surfaces contaminated with multidrug-resistant organisms (MDROs), and enhanced environmental disinfection is linked to reduced HAI rates. Recently, more focus has been placed on emerging disinfection technologies, such as UV light-producing portable device that emits light at a wavelength of 222 nm, which has previously demonstrated germicidal capabilities at short contact times. In this study, we aim i) to evaluate the efficacy of a filtered far-UV-C handheld device (FFUHH) to reduce bacterial loads on high-touch surfaces in clinical workrooms in a cancer center, and ii) to isolate, identify and establish a genetic relationship between these environmental clinically significant pathogens and the ones recovered from patients. Methods: Samples were collected weekly on a rotating schedule over a 24-week period from five high-touch items (dictation device, mouse, armchair, desk, and keyboard) in multiple clinical work rooms on hematologic malignancy and stem cell transplant units. Contact plates for colony count and swabs were collected pre- and post-intervention with the FFUHH on standardized adjacent areas respectively for each surface. The swabs were enriched and cultured on selective media to isolate clinically significant pathogens. Whole genome sequencing (WGS) was then performed on environmental pathogens validated by MALDI-TOF as well as clinical samples collected from patients in the same unit around the time of environmental sample collection. Results: A total of 440 plates, 220 pre- and 220 post-interventions, were collected and analyzed. The highest mean colony count pre-treatment was detected from the armchairs and the lowest for the keyboards. The mean reduction of colony forming units (CFUs) ranged between 53% for the keyboard and 83% for the mouse. The reduction was statistically significant across all surfaces with P values < 0.05, except for the keyboard (Figure 1). We isolated many pathogens of the human microbiota identified by MALDI-TOF such as Micrococcus luteus, S. capitis as well as methicillin-resistant S. epidermidis, S. haemolyticus and S. hominis. We also identified several Candida parapsilosis, Pseudomonas stutzeri, one Listeria grayi and one Acinetobacter baumanni. Finally, WSG allowed us to further characterize an environmental multi-drug resistant S. epidermidis ST5 strain associated with patient bacteremia, and ST16 strains detected on surfaces both pre- and post-FFUHH treatment. Conclusion: The FFUHH effectively reduced the microbial burden on high-touch surfaces in clinical workrooms on hematologic malignancy and stem cell units.

OBJECTIVES:. Occurrence of post-intubation laryngotracheal stenosis (LTS) with respect to COVID-19 status. DESIGN:. Retrospective cross-sectional inpatient database. SETTING:. Eleven Midwest academic and community hospitals, United States. PATIENTS:. Adults, mechanically ventilated, from January 2020 to August 2022, who were subsequently readmitted within 6 months with a new diagnosis of LTS. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Six thousand eight hundred fifty-one COVID-19 negative and 1316 COVID-19 positive patients were intubated and had similar distribution by age (median 63.77 vs. 63.16 yr old), sex (male, 60.8%; n = 4173 vs. 60%; n = 789), endotracheal tube size (≥ 7.5, 75.8%; n = 5192 vs. 75.5%; n = 994), and comorbidities. The ICU length of stay (median [interquartile range (IQR)], 7.23 d [2.13–16.67 d] vs. 3.95 d [1.91–8.88 d]) and mechanical ventilation days (median [IQR], 5.57 d [1.01–14.18 d] vs. 1.37 d [0.35–4.72 d]) were longer in the COVID-19 positive group. The occurrence of LTS was double in the COVID-19 positive group (12.7%, n = 168 vs. 6.4%, n = 440; p < 0.001) and was most commonly diagnosed within 60 days of intubation. In multivariate analysis, the risk of LTS increased by 2% with each additional ICU day (hazard ratio [HR], 1.02; 95% CI, 1.02–1.03; p < 0.001), by 3% with each additional day of ventilation (HR, 1.03; 95% CI, 1.02–1.04; p < 0.001), and by 52% for each additional reintubation (HR, 1.52; 95% CI, 1.36–1.71; p < 0.001). We observed no significant association COVID-19 status and risk of LTS. CONCLUSIONS:. The occurrence of post-intubation LTS was double in a COVID-19 positive cohort, with higher risk with increasing number of days intubated, days in the ICU and especially with the number of reintubations. COVID-19 status was not an independent risk factor for LTS.

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques, hyperphosphorylated tau protein, and neurofibrillary tangles in the brain. The overexpression of amyloid-β precursor protein (APP) in an AD brain results in the binding of APP intracellular domain (AICD) to Fe65 protein via the C-terminal Fe65-PTB2 interaction, which then triggers the secretion of amyloid-β and the consequent pathogenesis of AD. Apparently, targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for AD. Recently, exosome, a type of extracellular vesicle with diameter around 30–200 nm, has gained much attention as a potential delivery tool for brain diseases, including AD, due to their ability to cross the blood–brain barrier, their efficient uptake by autologous cells, and their ability to be surface-modified with target-specific receptor ligands. Here, the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65, enabled the development of a novel exosome-based targeted drug delivery system, which carried Corynoxine-B (Cory-B, an autophagy inducer) to the APP overexpressed-neuron cells in the brain of AD mice. The Fe65-engineered HT22 hippocampus neuron cell-derived exosomes (Fe65-EXO) loaded with Cory-B (Fe65-EXO-Cory-B) hijacked the signaling and blocked the natural interaction between Fe65 and APP, enabling APP-targeted delivery of Cory-B. Notably, Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells, leading to amelioration of the cognitive decline and pathogenesis in AD mice, demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.

Three-dimensional (3D) spheroid models are crucial for cancer research, offering more accurate insights into tumour biology and drug responses than traditional 2D cell cultures. However, inconsistent and low-throughput spheroid production has hindered their application in drug screening. Here, we present an automated high-throughput platform for a spheroid selection, fabrication, and sorting system (SFSS) to produce uniform gelatine-encapsulated spheroids (GESs) with high efficiency. SFSS integrates advanced imaging, analysis, photo-triggered fabrication, and microfluidic sorting to precisely control spheroid size, shape, and viability. Our data demonstrate that our SFSS can produce over 50 GESs with consistent size and circularity in 30 min with over 97% sorting accuracy while maintaining cell viability and structural integrity. We demonstrated that the GESs can be used for drug screening and potentially for various assays. Thus, the SFSS could significantly enhance the efficiency of generating uniform spheroids, facilitating their application in drug development to investigate complex biological systems and drug responses in a more physiologically relevant context.

IntroductionThere have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening.MethodsBetween August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma.ResultsOf the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants.ConclusionUse of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.

Abstract. Theological anthropology is not a new theme in the discussion of Christian theology. The Christian theologians since the early period have given serious thought to the theme. However, many people do not know that the development of theological anthropological thought is not as simple as imagined. Aspects of anthropology associated with theology from early Christianity to the Middle Ages are very different from what is developed during the Enlightenment until todaywhen anthropology has become one of the established scientific disciplines. This study used a critical descriptive-analytical method to examine the development of Christian theological anthropological thought throughout the history of Christianity to this day. The results of the study indicated that the struggle of theological anthropological thought is present as an effort to answer challenges in a certain context and time. Abstrak. Antropologi Teologis bukanlah sebuah tema baru dalam diskusi teologi Kristen. Para pemikir Kristen sejak periode awal telah memberikan pemikiran yang serius terkait tema tersebut. Hanya saja, banyak pihak yang tidak mengetahui bahwa perkembangan pemikiran antropologi teologis tidak sesederhana seperti apa yang dibayangkan. Aspek antropologi yang dikaitkan dengan teologi pada periode Awal Kristianitas sampai Abad-abad Pertengahan sangat berbeda dengan apa yang ditemukan masa Pencerahan sampai hari ini, ketika antropologi telah menjadi salah satu bidang keilmuan yang mapan. Penelitian ini menggunakan metode deskriptif-analitis yang kritis untuk menelaah perkembangan pemikiran Antropologi Teologis Kristen di sepanjang sejarah Kristianitas sampai hari ini. Hasil penelitian menunjukkan bahwa pergulatan pemikiran Antropologi Teologis hadir sebagai upaya untuk menjawab tantangan dalam konteks dan waktu tertentu.

Rationale & Objective: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT). Study Design: Retrospective observational cohort study Setting & Participants: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018. Predictors: Demographic and clinical characteristics of patients with CKD. Outcomes: Hospital admissions. Analytical Approach: We evaluated the association of demographic and clinical features with hospitalizations, length of hospital stay, and cost. Results: Approximately 81.5% of the patients were admitted at least once, with 42,283 admissions, costing Australian dollars (AUD) 231 million. The average number of admissions per person-year was 1.7, and the cost was AUD 9,060, 10 times and 2 times their Australian averages, respectively. Single (1-day) admissions constituted 59.2% of all the hospital episodes, led by neoplasms (largely chemotherapy), anemia, CKD-related conditions and eye conditions (largely cataract extractions), but only 14.8% of the total costs. Approximately 41% of admissions were >1-day admissions, constituting 85.2% of the total costs, with cardiovascular conditions, respiratory conditions, CKD-related conditions, and injuries, fractures, or poisoning being the dominant causes. Readmission within 30 days of discharge constituted >42% of the admissions and 46.8% costs. Admissions not directly related to CKD constituted 90% of the admissions and costs. More than 40% of the admissions and costs were through the emergency department. Approximately 19% of the hospitalized patients and 27% of the admissions did not have kidney disease mentioned as either principal or associate causes. Limitations: Variable follow-up times because of different dates of consent. Conclusions: The hospital burden of patients with CKD is mainly driven by complex multiday admissions and readmissions involving comorbid conditions, which may not be directly related to their CKD. Strategies to prevent these complex admissions and readmissions should minimize hospital costs and outcomes. Plain-Language Summary: We analyzed primary causes, types, and costs of hospitalizations among 7,201 patients with chronic kidney disease (CKD) from renal speciality clinics across Queensland, Australia, over an average follow-up of 3.54 years. The average annual cost per person was $9,060, and was the highest in those with more advanced CKD, higher age, and with diabetes. More than 85% of costs were driven by more complex hospitalizations with longer length of stay. Cardiovascular disease was the single largest contributor for hospitalizations, length of hospital stay, and total costs. Readmission within 30 days of discharge, particularly for the same disorder, and multiday admissions should be the main targets for mitigation of hospital costs in this population.

Abstract Background Fulminant myocarditis is a clinical syndrome associated with threatening dysrhythmia which temporary pacemaker can be used for life-saving support. As a method of physiological pacing, His bundle pacing (HBP) maintain better cardiac synchronization than traditional right ventricular (RV) pacing. Case presentation It’s a severe case of fulminant myocarditis in a 41-year-old patient who presented for recurrent arrhythmias with hemodynamic instability. Temporary His bundle pacing combined with optimal medical therapy and extracorporeal membrane oxygenators (ECMO) supported him through his critical period of hospitalization. Conclusions During 1-year follow up, the cardiac function recovery was obvious without any pacing related complications. Echocardiography showed better atrioventricular and intra-ventricular synchronization during HBP in DDD mode. This is the first reported case of temporary His-purkinje conduction system pacing used for severe fulminant myocarditis.

Abstract Background A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. Methods VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. Discussion Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. Trial registration Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

Modern economies are centered on electricity, which is also contributing to an increasing amount of energy services. As a result of increased household incomes, electrification of transport and rising demand for digital connected devices and air conditioning, there will be a rise in the need for energy. Residential electricity consumption in India has tripled over the past few decades with houses having access to uninterrupted power supply. This study is conducted in order to understand the determinants of electricity consumption such as income, family size, stock of electrical appliances, size of dwellings and their influence on consumer’s electricity consumption. It also seeks to examine if the consumers are willing to reduce their electricity consumption and are interested in shifting to renewable energy resources considering the costs involved in shifting to more sustainable energies. Due to the nature of power, which is invisible from the moment it was discovered, as well as consumer attitudes and behavior, saving electricity may appear to be a challenging undertaking. However, if the consumer acquires a basic understanding of what electricity is, how it is utilized, and, more significantly, how energy is wasted, the problem might become very simple. This will make consumers more aware of wasteful electricity use and perhaps encourage them to modify their daily consumption of electricity.

Abstract In this paper, we address the problem that standard stochastic Landau-Lifshitz-Gilbert (sLLG) simulations typically produce results that show unphysical mesh-size dependence. The root cause of this problem is that the effects of spin-wave fluctuations are ignored in sLLG. We propose to represent the effect of these fluctuations by a full-spin-wave-scaled stochastic LLG, or FUSSS LLG method. In FUSSS LLG, the intrinsic parameters of the sLLG simulations are first scaled by scaling factors that integrate out the spin-wave fluctuations up to the mesh size, and the sLLG simulation is then performed with these scaled parameters. We developed FUSSS LLG by studying the Ferromagnetic Resonance (FMR) in Nd2Fe14B cubes. The nominal scaling greatly reduced the mesh size dependence relative to sLLG. We then performed three tests and validations of our FUSSS LLG with this modified scaling. (1) We studied the same FMR but with magnetostatic fields included. (2) We simulated the total magnetization of the Nd2Fe14B cube. (3) We studied the effective, temperature- and sweeping rate-dependent coercive field of the cubes. In all three cases, we found that FUSSS LLG delivered essentially mesh-size-independent results, which tracked the theoretical expectations better than unscaled sLLG. Motivated by these successful validations, we propose that FUSSS LLG provides marked, qualitative progress towards accurate, high precision modeling of micromagnetics in hard, permanent magnets.

Diabetic neuropathy (DN) is a long-term complication of diabetes mellitus, affecting different periphery nerve systems including sensory and motor neurons. Hyperglycemia is the major cause of DN with symptoms such as weakness of balance or coordination, insensitivity to sensation, weakness of the muscles as well as numbness and pain in limbs Analgesic drug such as opioids can be effective to relief neuropathy pain but there is no effective treatment. Adiponectin is an anti-diabetic adipokine, which possesses insulin-sensitizing and neuroprotective effects. In this project, we aim to identify an agent which is dual acting to opioid and adiponectin receptors. Within a virtual screening repositioning campaign, a large collection of compounds with different structures comprehensive of adipoRon-like piperidine derivatives was screened by docking. Recently developed opioid receptor benzomorphanic agonists finally emerged as good ligands to adiponectin receptors showing some 2D and 3D structural similarities with AdipoRon. Particularly, we have identified (+)-MML1017, which has high affinity to the same binding domain of AdipoR1 and AdipoR2 as AdipoRon. Our western blot results indicate (+)-MML1017 activates AMPK phosphorylation through both adipoR1 and adipoR2 in neuronal cell line. Moreover, pretreatment of (+)-MML1017 can improve the cell viability with motor neurons under hyperglycermic conditions. The (+)-MML1017 also activates μ-opioid receptor cells in a concentration-dependent manner. Our study identified a novel compound having dual activity on opioid receptors and adiponectin receptors that may have analgesic effects and neuroprotective effects to treat diabetic neuropathy.

This paper is an attempt to find out the canonical meaning of the insertion of the text of Deuteronomy 1: 1-8 in the overall framework of Deuteronomy. The method used in this research is canonical hermeneutics developed by Brevard S. Childs, this approach enables the interpreter to see the intent of the editor of the Scriptures in the preparation of text sequences in such a way as to the perspective of the final canon. The canonical analysis shows that Deuteronomy 1: 1-8 is the initial part of the minor form (chapters 1-4) that is deliberately inserted and placed at the front as a close link to the previous book (even the first four books of the holy book) and is both an introduction and legitimacy of authority Deuteronomy even for the whole Deuteronomic History. This text comes from the editor of the exile and gives a message of new hope for the exiled Israeli community.This paper is an attempt to find out the canonical meaning of the insertion of the text of Deuteronomy 1: 1-8 in the overall framework of Deuteronomy. The method used in this research is canonical hermeneutics developed by Brevard S. Childs, this approach enables the interpreter to see the intent of the editor of the Scriptures in the preparation of text sequences in such a way as to the perspective of the final canon. The canonical analysis shows that Deuteronomy 1: 1-8 is the initial part of the minor form (chapters 1-4) that is deliberately inserted and placed at the front as a close link to the previous book (even the first four books of the holy book) and is both an introduction and legitimacy of authority Deuteronomy even for the whole Deuteronomic History. This text comes from the editor of the exile and gives a message of new hope for the exiled Israeli community.

Public Dental health must be maintained from an early age. However, it is not easy to make the children interested, understand, and aware of dental health. This paper discussed alternative methods for educating the children using IRVO model in augmented reality technology-based educational games. The game was built from several materials consisting of dental health education recommended by the dentist. Some of the interactions represented in the game application consist of point of view, selection and release, event creation, and manipulation. This educational game is implemented using the 3DS Max and D-Fusion Studio. This game has been approved for counsellors such as dentists, nurses, community health workers, and children. According to the resulting test, more than 75% of the dentists and children are interested in using this game and declared that they could use this application easily.

The wasp genus Psenulus is the most diverse genus of the family Psenidae in the superfamily Apoidea, with its diversity peaking in the Oriental realm. Six species of the genus are here recorded for the first time from the Hong Kong SAR. Three of these, Psenulus ephippius sp. nov., Psenulus gibbus sp. nov. and Psenulus pallens sp. nov. are described as new to science. An identification key, figures for all taxa recorded in Hong Kong and phenology of five of the six species are also provided.

Abstract Background Renal biopsy is often required to obtain information for diagnosis, management and prognosis of kidney disease that can be broadly classified into acute kidney injury (AKI) and chronic kidney disease (CKD). The most common conditions identified on renal biopsy are glomerulonephritis and tubulo-interstitial disorders. There is a paucity of information on management strategies and therapeutic outcomes in AKI and CKD patients. A renal biopsy registry will provide information on biopsy-proven kidney disorders to improve disease understanding and tracking, healthcare planning, patient care and outcomes. Methods A registry of patients, that includes biopsy-proven kidney disease, was established through the collaboration of nephrologists from Queensland Hospital and Health Services and pathologists from Pathology Queensland services. The registry is in keeping with directions of the Advancing Kidney Care 2026 Collaborative, established in September 2018 as a Queensland Health initiative. Phase 1 of the registry entailed retrospective acquisition of data from all adult native kidney biopsies performed in Queensland, Australia, from 2002 to 2018. Data were also linked with the existing CKD.QLD patient registry. From 2019 onwards, phase 2 of the registry involves prospective collection of all incident consenting patients referred to Queensland public hospitals and having a renal biopsy. Annual reports on patient outcomes will be generated and disseminated. Discussion Establishment of the Queensland Renal Biopsy Registry (QRBR) aims to provide a profile of patients with biopsy-proven kidney disease that will lead to better understanding of clinico-pathological association and facilitate future research. It is expected to improve patient care and outcomes.

Progressive conduction system disease affects patients with transthyretin cardiac amyloidosis, often requiring permanent pacing as the His-Purkinje system is affected. We present a case of left bundle branch pacing in a patient with transthyretin cardiac amyloidosis and infra-Hisian conduction disease with a favorable improvement in cardiac function and stable pacing thresholds. (Level of Difficulty: Intermediate.)

Samples from the Genesis Solar Wind Sample Return (NASA Discovery 5) are a unique opportunity to study the initial stages of space weathering, i.e., the physical and chemical effects of solar-wind irradiation. Arrays of collectors containing multiple materials were each exposed to a different solar-wind regime (fast, slow, bulk, or coronal mass ejection) at the L1 point for long durations (years). Materials exposed to the solar wind included metals, semiconductors, and insulators. Although the time of exposure was obviously short relative to samples having extraterrestrial origins, optical properties, surface chemical properties, and matrix structure have changed in many collectors due to exposure to solar wind. The thickness of amorphous zones, where present, appears to correspond with the depth of the peak of the solar-wind H distribution in each regime. Damage from high-energy particles was negligible because the collectors were 700 μ m or less in thickness and shielded from the back by the spacecraft. Micrometeorite impacts and sputtering were also negligible because of the short exposure times. Our current results are preliminary: We hope future workers will extend this study both to support Genesis characterization efforts and to further understand space-weathering processes on a geologic timescale.

NSTEACS is subset of ACS that may present with a wide degree of stenosis from normal vessels to severe obstruction. Identification of which population of NSTEACS that has normal vessels has attracted a great attention. Several trials on non-invasive imaging such as coronary CT have been largely investigated. Current available trials have showed that coronary CT is accurately identify significant stenosis in patients with NSTEACS thus can be used to rule out the disease and reduce the need and duration of unneeded antithrombotic. However, several limitations of the studies has to be taken into account when translating into clinical practice. Nevertheless, current evidence are showing promising results on the role of coronary CT in management of NSTEACS.

Abstract Background Microglia-mediated neuroinflammation is important in Alzheimer’s disease (AD) pathogenesis. Extracellular deposition of β-amyloid (Aβ), a major pathological hallmark of AD, can induce microglia activation. Adiponectin (APN), an adipocyte-derived adipokine, exerts anti-inflammatory effects in the periphery and brain. Chronic APN deficiency leads to cognitive impairment and AD-like pathologies in aged mice. Here, we aim to study the role of APN in regulating microglia-mediated neuroinflammation in AD. Methods Inflammatory response of cultured microglia (BV2 cells) to AβO and effects of APN were studied by measuring levels of proinflammatory cytokines (tumor necrosis factor α [TNFα] and interleukin-1β [IL-1β]) in cultured medium before and after exposure to AβO, with and without APN pretreatment. Adiponectin receptor 1 (AdipoR1) and receptor 2 (AdipoR2) were targeted by small interference RNA. To study the neuroprotective effect of APN, cultured HT-22 hippocampal cells were treated with conditioned medium of AβO-exposed BV2 cells or were co-cultured with BV2 cells in transwells. The cytotoxicity of HT-22 hippocampal cells was assessed by MTT reduction. We generated APN-deficient AD mice (APN−/−5xFAD) by crossing APN-knockout mice with 5xFAD mice to determine the effects of APN deficiency on microglia-mediated neuroinflammation in AD. Results AdipoR1 and AdipoR2 were expressed in BV2 cells and microglia of mice. Pretreatment with APN for 2 h suppressed TNFα and IL-1β release induced by AβO in BV2 cells. Additionally, APN rescued the decrease of AMPK phosphorylation and suppressed nuclear translocation of nuclear factor kappa B (NF-κB) induced by AβO. Compound C, an inhibitor of AMPK, abolished these effects of APN. Knockdown of AdipoR1, but not AdipoR2 in BV2 cells, inhibited the ability of APN to suppress proinflammatory cytokine release induced by AβO. Moreover, pretreatment with APN inhibited the cytotoxicity of HT-22 cells co-cultured with AβO-exposed BV2 cells. Lastly, APN deficiency exacerbated microglia activation in 9-month-old APN−/−5xFAD mice associated with upregulation of TNFα and IL-1β in the cortex and hippocampus. Conclusions Our findings demonstrate that APN inhibits inflammatory response of microglia to AβO via AdipoR1-AMPK-NF-κB signaling, and APN deficiency aggravates microglia activation and neuroinflammation in AD mice. APN may be a novel therapeutic agent for inhibiting neuroinflammation in AD.

Abstract Background Workforce shortages, particularly in rural areas, limit the delivery of health services in Zambia. Policymakers and researchers co-created this study to identify potential non-monetary employment incentives and assess their cost-effectiveness to attract and retain public sector health workers to the rural areas of Zambia. Methods The study consisted of two key phases: a discrete choice experiment (DCE), preceded by a qualitative component to inform DCE questionnaire development. Firstly, in qualitative interviews with 25 health workers and focus group discussions (FGDs) with 253 health students, participants were asked to discuss job attributes and potential incentives that would influence their job choices. Based on this exercise and in consultation with policymakers, job attributes were selected for inclusion in a discrete choice experiment (DCE) questionnaire. Secondly, this questionnaire, consisting of hypothetical job “choice sets,” was presented to 474 practicing health workers and students. A conditional logit regression model was applied to the data from this DCE questionnaire to estimate preferences for various job attributes. Using administrative data, we estimated the cost of implementing potential attraction and retention strategies per health worker year worked. Results Although health workers preferred urban jobs to rural jobs (OR 1.39, 95% CI 1.11–1.75), employment incentives influenced health workers’ decision to choose rural jobs. If superior housing was offered in a rural area compared to a basic housing allowance in an urban job, participants would be five times as likely to choose the rural job (OR 5.04, 95% CI 4.12–6.18). Education incentives and facility-based improvements also increased the likelihood of rural job uptake. Housing benefits were estimated to have the lowest total costs per health worker year worked, and offer high value in terms of cost per percentage point increase in rural job uptake. Conclusions Non-monetary incentives such as housing, education, and facility improvements can be important motivators of health worker choice of location and could mitigate rural health workforce shortages. These results can provide valuable insight into the types of job attributes and incentives that are most likely to be effective in attracting and retaining health workers in rural areas.

In an energy harvesting wireless sensor node (EHWSN), balance of energy harvested and consumption using dynamic energy management to achieve the goal of perpetual operation is one of the most important research topics. In this study, a novel fuzzy Q-learning (FQL)-based dynamic energy management (FQLDEM) is proposed in adapting its policy to the time varying environment, regarding both the harvested energy and the energy consumption of the WSN. The FQLDEM applies Q-learning to train, evaluate, and update the fuzzy rule base and then uses the fuzzy inference system (FIS) for determining the working duty cycle of the sensor of the EHWSN. Through the interaction with the energy harvesting environment, the learning agent of the FQL will be able to find the appropriate fuzzy rules in adapting the working duty cycle for the goal of energy neutrality such that the objective of perpetual operation of the EHWSN can be achieved. Experimental results show that the FQLDEM can maintain the battery charge status at a higher level than other existing methods did, such as the reinforcement learning (RL) method and dynamic duty cycle adaption (DDCA), and achieve the perpetual operation of the EHWSN. Furthermore, experimental results for required on-demand sensing measurements exhibit that the FQLDEM method can be slowly upgraded to meet 65% of the service quality control requirements in the early stage, which outperforms the RL-based and DDCA methods.

BACKGROUND:Studies estimate that the number of cancer survivors will double by 2050 due to improvements in diagnostic accuracy and treatment efficacy. Despite the growing population of cancer survivors, there is a paucity of research regarding how these individuals experience the transition from active treatment to long-term surveillance. While research has explored this transition from more organized venues, such as support groups for cancer survivors, this paper explores the discourses surrounding cancer survivorship on social media, paying particular attention to how individuals who identify as cancer survivors represent their experience. METHODS:We identified social media posts relating to cancer survivorship on Twitter and Instagram in early June 2018, in order to coincide with National Cancer Survivorship Day on June 3, 2018. We used nine pre-selected hashtags to identify content. For each hashtag, we manually collected the 150 most recent posts from Twitter and the 100 most recent plus the top 9 posts from Instagram. Our preliminary sample included 1172 posts; after eliminating posts from one hashtag due to irrelevance, we were left with 1063 posts. We randomly sampled 200 of these to create a subset for analysis; after review for irrelevant posts, 193 posts remained for analysis (118 from Instagram and 75 from Twitter). We utilized a grounded theory approach to analyze the posts, first open-coding a subset to develop a codebook, then applying the codebook to the rest of the sample and finally memo writing to develop themes. RESULTS:Overall, there is substantial difference in the tone and thematic content between Instagram and Twitter posts, Instagram takes on a more narrative form that represents journeys through cancer treatment and subsequent survivorship, whereas Twitter is more factual, leaning towards advocacy, awareness and fundraising. In terms of content type, 120 posts (62%) of the sample were images, of which 42 (35%) were images of the individual posting and 28 (23%) were images of patients posted by family or friends. Of the remaining images, 14 (12%) were of support groups and 7 (6%) were of family or friends. We identified four salient themes through analysis of the social media posts from Twitter and Instagram: social support, celebrating milestones and honoring survivors, expressing identity, and renewal vs. rebirth. DISCUSSION:We observed a marked relationship between physical appearance, functional status and survivorship. Additionally, our findings suggest the importance of social support for cancer patients and survivors as well as the role social media can pay in identity formation. CONCLUSION:Our findings suggest that individuals who identify as survivors on social media define their identity fluidly, incorporating elements of physical, emotional and psychological health as well as autonomy.

BackgroundCampylobacter jejuni is the most common bacterial cause of human infectious intestinal disease.MethodsWe genome sequenced 601 human C. jejuni isolates, obtained from two large prospective studies of infectious intestinal disease (IID1 [isolates from 1993-1996; n = 293] and IID2 [isolates from 2008-2009; n = 93]), the INTEGRATE project [isolates from 2016-2017; n = 52] and the ENIGMA project [isolates from 2017; n = 163].ResultsThere was a significant increase in the prevalence of the T86I mutation conferring resistance to fluoroquinolone between each of the three later studies (IID2, INTEGRATE and ENIGMA) and IID1. Although the distribution of major multilocus sequence types (STs) was similar between the studies, there were changes in both the abundance of minority STs associated with the T86I mutation, and the abundance of clones within single STs associated with the T86I mutation.DiscussionFour population-based studies of community diarrhoea over a 25 year period revealed an increase over time in the prevalence of the T86I amongst isolates of C. jejuni associated with human gastrointestinal disease in the UK. Although associated with many STs, much of the increase is due to the expansion of clones associated with the resistance mutation.

This study examines the perceptions of preparers of financial reports towards the issues surrounding corporate quarterly financial reporting in Malaysia. Questionnaires were mailed to chief financial officers of the Kuala Lumpur Stock Exchange (KLSE)1 listed companies, from whom 106 usable responses were gathered. The findings provide evidence that some preparers are not keen of the idea of quarterly reporting, despite the enforcement of the requirement. However, a majority of preparers are content with the current allowable reporting lag of two months, satisfied with the current content of the quarterly reports, and agree that management should at least discuss the quarterly results with the auditors. With respect to other matters, preparers expressed the view that the quarterly reports are reliable. However, there is also evidence that the first three quarterly reports are perceived to be less reliable than the fourth quarterly reports. The findings serve as an avenue for more research on quarterly financial reporting in Malaysia and other jurisdictions.

The study of laser-induced ultrafast magnetization dynamics is crucial for the development of information recording technology. Due to the complex mechanism, there is still a lack of comprehensive understanding for ultrafast magnetization dynamics. As an essential stage of laser-induced ultrafast magnetization switching process, the transient ferromagnetic like state (TFLS), has attracted much attention. Different from other studies on TFLS through the difference of magnetization dynamics between rare-earth and transition-metal, our study mainly focuses on the influence of energy injection and relaxation on TFLS in the process of ultrafast magnetization dynamics. The influence of various parameters on the formation of energy exchange dependent TFLS is studied. The results of simulation well support our view. Understanding the mechanism behind the TFLS is of great significance to promote the application of laser-induced ultrafast magnetization switching.

Abstract Background There is an increasing global movement of foreign female entertainment workers (FEWs), a hard-to-reach population vulnerable to HIV/STIs. This paper described the needs assessment phase before intervention implementation where the socio-organisation, sexual risk behaviours and access to health services of foreign FEWs in Singapore were explored. We also highlighted how qualitative inquiry, census enumeration technique and community-based engagement approaches were used to gain access and to develop a culturally appropriate STI prevention intervention. Methods In-depth interviews, observations, informal conversational interviews, mystery client and critical incident technique were used. We estimated the size of FEW population using the census enumeration technique. The findings were used to inform intervention development and implementation. Results We estimated 376 Vietnamese and 330 Thai FEWs in 2 geographical sites where they operated in Singapore. Their reasons for non-condom use included misconceptions on the transmission and consequences of STI/HIV, low risk perception of contracting HIV/STI from paid/casual partner, lack of skills to negotiate or to persuade partner to use condom, unavailability of condoms in entertainment establishments and fear of the police using condom as circumstantial evidence. They faced difficulties in accessing health services due to fear of identity exposure, stigmatisation, cost and language differences. To develop the intervention, we involved FEWs and peer educators, and ensured that the intervention was non-stigmatising and met their needs. To foster their participation, we used culturally-responsive recruitment strategies, and ensured that the trial was anonymous and acceptable to the FEWs. These strategies were effective as we achieved a participation rate of 90.3%, a follow-up rate of 70.5% for the comparison and 66.8% for the intervention group. The interventions group reported a significant increase in consistent condom use with a reduction in STI incidence compared to no significant change in the comparison group. Conclusions The qualitative inquiry approaches to gain access, to foster participation and to develop a culturally appropriate intervention, along with the census enumeration technique application to estimate the FEW population sizes has led to successful intervention implementation as well as safer sexual behaviour and STI incidence reduction. Trial registration ClinicalTrials.gov, NCT02780986. Registered 23 May 2016 (retrospectively registered).

The present study makes an effort to understand the damage of earthen dams under static and seismic loading condition. To make the investigation more realistic, behaviour of earthen dams considering the occurrence of a phreatic line indicating the submerged zone due to seepage within the dam body is considered. In case of earthen dams, homogeneous or nonhomogeneous, the consideration of the occurrence of a phreatic line or seepage line through the dam body is an important part of the earthen dam design methodology. The impervious material properties in the submerged zone below the phreatic line due to seepage may differ a lot in magnitudes as compared to the value of the same materials lying above this line. Hence, to have the exact stress distribution scenarios within the earthen dam, the different material properties above and below the phreatic line are considered in this present study. The study is first carried out by two-dimensional as well as three-dimensional finite element analysis under static loading condition. The work is further extended to observe the effect of seepage due to the consideration of the phreatic line on dynamic characteristics of earthen dams. Free vibration analysis and seismic analysis based on the Complete Quadratic Combination (CQC) method by considering twodimensional and three-dimensional modeling are carried out to present the frequencies, mode shapes and the stress distribution pattern of the earthen dam.

Liraglutide is an effective drug for the treatment of type 2 diabetes mellitus (T2DM). The aim of this review is to collate evidence on the real-world clinical effectiveness of liraglutide from the published Indian studies. A review of publications was conducted to identify observational studies that assessed the effectiveness of liraglutide among Indian T2DM. Total ten publications were retrieved and these observational studies are compared with the results of the liraglutide randomized controlled trial (RCT) program (Liraglutide Effect and Action in Diabetes [LEAD]). Liraglutide therapy demonstrated HbA1c reduction in the Indian population up to 2.26% and 2.54%, over 24 and 52 weeks, respectively. Among the LEAD trials, the HbA1c reduction at 24 weeks was maximum in LEAD-4 with 1.5% reduction at both doses used (1.2 and 1.8 mg) and up to 1.14% in LEAD-3 with a dose of 1.8 mg. The weight loss among Indian subjects was generally around 5 kg or more with maximum weight loss of 8.6 kg over 24 weeks. The maximal weight loss in LEAD studies was less than 3 kg with an exception of 3.24 kg in LEAD-6. In over 52 weeks of liraglutide therapy among Indian subjects, mean weight loss was 7.4 kg, which was 3.5 times more than of LEAD program. Two Indian observational studies also demonstrated significant weight loss among nondiabetic obese subjects at a much lower than that of 3 mg anti-obesity dose. Gastrointestinal (GI) events are the commonly reported adverse events with Indian studies as well as LEAD program. Liraglutide therapy produces better glycemic control and more weight loss among Indian T2DM subjects compared with RCTs conducted in western population with almost similar adverse consequences.

Given the prevalence of medication nonadherence (Sabaté, 2003), clinicians and public health researchers are compelled to design, implement, evaluate, and iterate strategies to improve fidelity to medication regimens. Although barriers to medication adherence range from the individual to the structural, addressing the ambiguity, technicality, and variability of traditional instructions are among the most actionable barriers to comprehension and adherence.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is now a standard of care to sample mediastinal lymph nodes and masses with high diagnostic accuracy and low complication rates. However, the procedure has potential complications that might be life-threatening. Here, we present the first case of Propionobacterium acnes (P. acnes) causing mediastinitis following EBUS-TBNA of a subcarinal lymph node.

High-throughput metabolomics can be used to optimize cell growth for enhanced production or for monitoring cell health in bioreactors. It has applications in cell and gene therapies, vaccines, biologics, and bioprocessing. NMR metabolomics is a method that allows for fast and reliable experimentation, requires only minimal sample preparation, and can be set up to take online measurements of cell media for bioreactor monitoring. This type of application requires a fully automated metabolite quantification method that can be linked with high-throughput measurements. In this review, we discuss the quantifier requirements in this type of application, the existing methods for NMR metabolomics quantification, and the performance of three existing quantifiers in the context of NMR metabolomics for bioreactor monitoring.