Analytically Solvable Asymptotic Model of Atrial Excitability

We report a three-variable simplified model of excitation fronts in human atrial tissue. The model is derived by novel asymptotic techniques \new{from the biophysically realistic model of Courtemanche et al (1998) in extension of our previous similar models. An iterative analytical solution of the model is presented which is in excellent quantitative agreement with the realistic model. It opens new possibilities for analytical studies as well as for efficient numerical simulation of this and other cardiac models of similar structure

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Patients with physical debility undergoing subacute physical rehabilitation following an acute hospital admission demonstrated improvement in cognitive functional task independence

Background: Hospitalised older adults often experience a decline in physical functioning and mobility in the lead up to (or during) an acute hospital admission. During acute illness and hospitalisation, older adults may also experience a decline or fluctuation in their cognitive functioning. Previous studies have demonstrated that patients with or without reduced cognitive functioning on admission to subacute inpatient rehabilitation have considerable potential to improve their physical functioning and quality of life

Additive effect of autologous platelet concentrates in treatment of intrabony defects : a systematic review and meta-analysis

The aim of the present review is to systematically evaluate the additive effect of autologous platelet concentrates (APCs) in treatment of intrabony defects when used along with other regenerative procedures and when used alone in terms of clinical and radiological outcomes. A search was performed in electronic databases (i.e., MEDLINE and the Cochrane Central Register of Controlled Trials) in order to identify randomized clinical trials (RCTs) assessing the additive efficacy of APCs for healing and regeneration of hard and soft tissues in patients undergoing regenerative surgical procedures for the treatment of intrabony defects, having a follow-up of at least 9\ua0months. Included studies underwent risk of bias assessment and data extraction. The main variables evaluated for efficacy were: pocket depth (PD), clinical attachment level (CAL), radiographic bone filling, and postoperative pain. The effect of APCs adjunct was evaluated for the following procedures: open flap debridement (OFD) alone, OFD plus grafting of the defect with autogenous bone or bone substitutes, and grafting in combination with a covering membrane for guided tissue regeneration (GTR). Platelet-rich fibrin (PRF) has a significant additive effect when used along with OFD. Platelet-rich plasma (PRP) has a significant additive effect when used along with bone grafts. Conversely, PRP was found to be ineffective when used in combination with GTR procedures. No study evaluated the effect of APCs on postoperative pain. Platelet-rich plasma may be used advantageously as an adjunct to grafting materials, but not in combination with GTR, for treatment of intrabony defects. Moreover, PRF can be effective as a sole regenerative material, in combination with OFD. There is still a lack of evidence regarding the effect of PRF in combination with grafting materials and GTR, the effect of other types of APCs such as plasma rich in growth factors, and the effect of APCs on postoperative pain

Efficient multispectral photodetection using Mn doped ZnO nanowires

10.1039/c2jm16698dJournal of Materials Chemistry22199678-9683JMAC

Physical and electrical properties of single Zn2 Sn O 4 nanowires

10.1149/1.3505875Electrochemical and Solid-State Letters141K5-K7ESLE