Symmetry effects on the static and dynamic properties of coupled magnetic oscillators

The effect of symmetry on the resonance spectra of antiferromagnetically coupled oscillators has attracted new interest with the discovery of symmetry-breaking induced anti-crossings. Here, we experimentally characterise the resonance spectrum of a synthetic antiferromagnet Pt/CoFeB/Ru/CoFeB/Pt, where we are able to independently tune the effective magnetisation of the two coupled magnets. To model our results we apply the mathematical methods of group theory to the solutions of the Landau Lifshitz Gilbert equation. This general approach, usually applied to quantum mechanical systems, allows us to identify the main features of the resonance spectrum in terms of symmetry breaking and to make a direct comparison with crystal antiferromagnets

Dynamic Profiling of β-Coronavirus 3CL Mpro Protease Ligand-Binding Sites

β-coronavirus (CoVs) alone has been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a backup against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensable role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide a comprehensive comparison of all nonredundant ligand-binding sites available for SARS-CoV2, SARS-CoV, and MERS-CoV Mpro. Extensive adaptive sampling has been used to investigate structural conservation of ligand-binding sites using Markov state models (MSMs) and compare conformational dynamics employing convolutional variational auto-encoder-based deep learning. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-CoV homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor

Cardioprotective effects of sphingosine-1-phosphate receptor immunomodulator fty720 in a clinically relevant model of cardioplegic arrest and cardiopulmonary bypass

Objective: FTY720, an immunomodulator derived from sphingosine-1-phosphate, has recently demonstrated its immunomodulatory, anti-inflammatory, anti-oxidant, anti-apoptotic and anti-inflammatory properties. Furthermore, FTY720 might be a key pharmacological target for preconditioning. In this preclinical model, we have investigated the effects of FTY720 on myocardium during reperfusion in an experimental model of cardioplegic arrest (CPA) and cardiopulmonary bypass. Methods: 30 Sprague-Dawley rats (300-350 g) were randomized into two groups: Group-A, treated with FTY720 1 mg/kg via intravenous cannulation, and Group-B, as control. After 15 min of treatment, rats underwent CPA for 30 min followed by initiation of extracorporeal life support for 2 h. Support weaning was done, and blood and myocardial tissues were collected for analysis. Hemodynamic parameters, inflammatory mediators, nitro-oxidative stress, neutrophil infiltration, immunoblotting analysis, and immunohistochemical staining were analyzed and compared between groups. Results: FTY720 treatment activated the Akt/Erk1/2 signaling pathways, reduced the level of inflammatory mediators, activated antiapoptotic proteins, and inhibited proapoptotic proteins, leading to reduced nitro-oxidative stress and cardiomyocyte apoptosis. Moreover, significant preservation of high-energy phosphates were observed in the FTY720-treated group. This resulted in improved recovery of left ventricular systolic and diastolic functions. Conclusion: The cardioprotective mechanism in CPA is associated with activation of prosurvival cell signaling pathways that prevents myocardial damage. FTY720 preserves high-energy phosphates attenuates myocardial inflammation and oxidative stress, and improves cardiac function

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

The effect of a patient centred care bundle intervention on pressure ulcer incidence (INTACT): a cluster randomised trial

Background: Hospital-acquired pressure ulcers are a serious patient safety concern, associated with poor patient outcomes and high healthcare costs. They are also viewed as an indicator of nursing care quality. Objective: To evaluate the effectiveness of a pressure ulcer prevention care bundle in preventing hospital-acquired pressure ulcers among at risk patients. Design: Pragmatic cluster randomised trial. Setting: Eight tertiary referral hospitals with >200 beds each in three Australian states. Participants: 1600 patients (200/hospital) were recruited. Patients were eligible if they were: ≥18 years old; at risk of pressure ulcer because of limited mobility; expected to stay in hospital ≥48 h and able to read English. Methods: Hospitals (clusters) were stratified in two groups by recent pressure ulcer rates and randomised within strata to either a pressure ulcer prevention care bundle or standard care. The care bundle was theoretically and empirically based on patient participation and clinical practice guidelines. It was multi-component, with three messages for patients’ participation in pressure ulcer prevention care: keep moving; look after your skin; and eat a healthy diet. Training aids for patients included a DVD, brochure and poster. Nurses in intervention hospitals were trained in partnering with patients in their pressure ulcer prevention care. The statistician, recruiters, and outcome assessors were blinded to group allocation and interventionists blinded to the study hypotheses, tested at both the cluster and patient level. The primary outcome, incidence of hospital-acquired pressure ulcers, which applied to both the cluster and individual participant level, was measured by daily skin inspection. Results: Four clusters were randomised to each group and 799 patients per group analysed. The intraclass correlation coefficient was 0.035. After adjusting for clustering and pre-specified covariates (age, pressure ulcer present at baseline, body mass index, reason for admission, residence and number of comorbidities on admission), the hazard ratio for new pressure ulcers developed (pressure ulcer prevention care bundle relative to standard care) was 0.58 (95% CI: 0.25, 1.33; p = 0.198). No adverse events or harms were reported. Conclusions: Although the pressure ulcer prevention care bundle was associated with a large reduction in the hazard of ulceration, there was a high degree of uncertainty around this estimate and the difference was not statistically significant. Possible explanations for this non-significant finding include that the pressure ulcer prevention care bundle was effective but the sample size too small to detect this

INTroducing A Care bundle To prevent pressure injury (INTACT) in at-risk patients: A protocol for a cluster randomised trial

Background Pressure injuries are a significant clinical and economic issue, affecting both patients and the health care system. Many pressure injuries in hospitals are facility acquired, and are largely preventable. Despite growing evidence and directives for pressure injury prevention, implementation of preventative strategies is suboptimal, and pressure injuries remain a serious problem in hospitals. Objectives This study will test the effectiveness and cost-effectiveness of a patient-centred pressure injury prevention care bundle on the development of hospital acquired pressure injury in at-risk patients. Design This is a multi-site, parallel group cluster randomised trial. The hospital is the unit of randomisation. Methods Adult medical and surgical patients admitted to the study wards of eight hospitals who are (a) deemed to be at risk of pressure injury (i.e. have reduced mobility), (b) expected to stay in hospital for ≥48 h, (c) admitted to hospital in the past 36 h; and (d) able to provide informed consent will be eligible to participate. Consenting patients will receive either the pressure injury prevention care bundle or standard care. The care bundle contains three main messages: (1) keep moving; (2) look after your skin; and (3) eat a healthy diet. Nurses will receive education about the intervention. Patients will exit the study upon development of a pressure injury, hospital discharge or 28 days, whichever comes first; transfer to another hospital or transfer to critical care and mechanically ventilated. The primary outcome is incidence of hospital acquired pressure injury. Secondary outcomes are pressure injury stage, patient participation in care and health care costs. A health economic sub-study and a process evaluation will be undertaken alongside the trial. Data will be analysed at the cluster (hospital) and patient level. Estimates of hospital acquired pressure injury incidence in each group, group differences and 95% confidence interval and p values will be reported. Discussion To our knowledge, this is the first trial of an intervention to incorporate a number of pressure injury prevention strategies into a care bundle focusing on patient participation and nurse–patient partnership. The results of this study will provide important information on the effectiveness and cost-effectiveness of this intervention in preventing pressure injuries in at-risk patients. If the results confirm the utility of the developed care bundle, it could have a significant impact on clinical practice worldwide