Multifractality and scale invariance in human heartbeat dynamics

Human heart rate is known to display complex fluctuations. Evidence of multifractality in heart rate fluctuations in healthy state has been reported [Ivanov et al., Nature {\bf 399}, 461 (1999)]. This multifractal character could be manifested as a dependence on scale or beat number of the probability density functions (PDFs) of the heart rate increments. On the other hand, scale invariance has been recently reported in a detrended analysis of healthy heart rate increments [Kiyono et al., Phys. Rev. Lett. {\bf 93}, 178103 (2004)]. In this paper, we resolve this paradox by clarifying that the scale invariance reported is actually exhibited by the PDFs of the sum of detrended healthy heartbeat intervals taken over different number of beats, and demonstrating that the PDFs of detrended healthy heart rate increments are scale dependent. Our work also establishes that this scale invariance is a general feature of human heartbeat dynamics, which is shared by heart rate fluctuations in both healthy and pathological states

Characterization of Retinal Structure in ATF6-Associated Achromatopsia.

PurposeMutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM.MethodsSeven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM.ResultsFoveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports.ConclusionsOur data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM

The Researcher Wellbeing Project Report

The Researcher Wellbeing Project (RWP) focused on understanding the potential impacts, including secondary trauma, of researching emotionally challenging topics; and establishing what, if anything, researchers have in place to help them cope and what they would like to be in place. The overwhelming reception the RWP has received from staff has been very positive, because it addresses a topic that has been “a really invisible issue” (Participant 22) within academia until very recently. The project involved 31 semi-structured interviews with researchers who did potentially emotionally challenging research. These participants were also asked to do follow-up questionnaires; 25 completed the coping mechanisms/interventions questionnaire and 20 completed the Secondary Trauma Scale. In this report, we outline the key findings of the RWP related to: (i) impacts and (ii) coping mechanisms and recommended support/interventions. The RWP identified that academics undertaking potentially distressing research in the majority are inspired and driven by the research they do. However, it in turn has substantial impacts on the researchers, most of whom had symptoms that could be linked to secondary trauma at varying degrees. How well researchers coped with such emotionally challenging research was not just about them as individuals. It was about how well they were supported by the systems that were around them. Thus, individual researchers’ knowledge, skills and experience contributed, alongside how effective supervisors/managers were in designing projects and managing teams/individuals, as well as how much positive/supportive interactions researchers got within teams, and how much thought and investment an institution put into how researchers were looked after. Ideally, institutions that undertake and fund research on emotionally challenging topics need to put plans in place to develop a well-funded strategy focused on prevention of and provision for distress and secondary trauma linked to emotionally challenging research. For institutions that are unable to do this fully, a phased approach working towards this would be a viable option. To help organisations to do this, the report provides guidance on Bronze, Silver and Gold levels that institutions can adopt to support academics

Making energy behaviour research relevant to policy: A tale of two studies

Within a context of shrinking government resources and greater pressure on academics and other researchers to generate ‘impact’ from (publically funded) research there is a greater need than ever to ensure that published research is readily usable by and relevant to policy end-users. Through examining and comparing two energy related evidence reviews commissioned by the UK government, this paper presents a set of recommendations for those researchers who seek to make their publications (in both the white and grey literature) more accessible, usable and relevant to those working in policy and practice domains

Expression of calcification and extracellular matrix genes in the cardiovascular system of the healthy domestic sheep (Ovis aries).

The maintenance of a healthy cardiovascular system requires expression of genes that contribute to essential biological activities and repression of those that are associated with functions likely to be detrimental to cardiovascular homeostasis. Vascular calcification is a major disruption to cardiovascular homeostasis, where tissues of the cardiovascular system undergo ectopic calcification and consequent dysfunction, but little is known about the expression of calcification genes in the healthy cardiovascular system. Large animal models are of increasing importance in cardiovascular disease research as they demonstrate more similar cardiovascular features (in terms of anatomy, physiology and size) to humans than do rodent species. We used RNA sequencing results from the sheep, which has been utilized extensively to examine calcification of prosthetic cardiac valves, to explore the transcriptome of the heart and cardiac valves in this large animal, in particular looking at expression of calcification and extracellular matrix genes. We then examined genes implicated in the process of vascular calcification in a wide array of cardiovascular tissues and across multiple developmental stages, using RT-qPCR. Our results demonstrate that there is a balance between genes that promote and those that suppress mineralization during development and across cardiovascular tissues. We show extensive expression of genes encoding proteins involved in formation and maintenance of the extracellular matrix in cardiovascular tissues, and high expression of hematopoietic genes in the cardiac valves. Our analysis will support future research into the functions of implicated genes in the development of valve calcification, and increase the utility of the sheep as a large animal model for understanding ectopic calcification in cardiovascular disease. This study provides a foundation to explore the transcriptome of the developing cardiovascular system and is a valuable resource for the fields of mammalian genomics and cardiovascular research

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.Postprint (published version

Meshes in Implant-Based Breast Reconstruction: The Science and Technology

Breast reconstruction is a common choice post mastectomy or breast-conserving surgery for breast cancer. Reconstructive options currently include implant-based and autologous reconstruction, with adjunctive use of surgical meshes. Acellular dermal matrices (ADMs) of both human and animal origin, and synthetic meshes are well-established for use in implant reconstruction. With ADMs, there is reduced risk of capsular contracture, providing a strong scaffold for prosthetic-based immediate reconstruction. Reduced seroma formation and infection has been demonstrated with synthetic mesh, thus both techniques proving advantageous. Use of mesh in implant-based reconstruction is a quickly evolving field, with hybrid meshes, 3D printed meshes and antibiotic-loaded meshes being investigated within the current literature. Whilst these surgical techniques are relatively new, they provide a new approach to many of the ethical issues currently surrounding use of surgical mesh

Concurrent behavioral and electrophysiological longitudinal recordings for in vivo assessment of aging

Electrophysiological and behavioral alterations, including sleep and cognitive impairments, are critical components of age-related decline and neurodegenerative diseases. In preclinical investigation, many refined techniques are employed to probe these phenotypes, but they are often conducted separately. Herein, we provide a protocol for one-time surgical implantation of EMG wires in the nuchal muscle and a skull-surface EEG headcap in mice, capable of 9-to-12-month recording longevity. All data acquisitions are wireless, making them compatible with simultaneous EEG recording coupled to multiple behavioral tasks, as we demonstrate with locomotion/sleep staging during home-cage video assessments, cognitive testing in the Barnes maze, and sleep disruption. Time-course EEG and EMG data can be accurately mapped to the behavioral phenotype and synchronized with neuronal frequencies for movement and the location to target in the Barnes maze. We discuss critical steps for optimizing headcap surgery and alternative approaches, including increasing the number of EEG channels or utilizing depth electrodes with the system. Combining electrophysiological and behavioral measurements in preclinical models of aging and neurodegeneration has great potential for improving mechanistic and therapeutic assessments and determining early markers of brain disorders

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Continuous Biosensing to Monitor Acute Systemic Inflammation, a Diagnostic Need for Therapeutic Guidance

Continuous monitoring of acute inflammation can become a very important next step for guiding therapeutic interventions in severely ill patients. This Perspective discusses the current medical need for patients with acute inflammatory diseases and the potential of continuous biosensing technologies. First, we discuss biomarkers that could help to monitor the state of a patient with acute systemic inflammation based on theoretical studies and empirical data. Then, based on the state of the art, we describe sensing strategies that could be applied for the continuous monitoring of acute inflammatory biomarkers, followed by challenges that must be overcome. Nanoswitch-based continuous biosensors enable suitable measurement frequencies but still lack sensitivity, while regeneration risks lower sensor reliability. Developments are still needed in bioreceptors and molecular architectures, regeneration techniques, combined with suitable sampling and sample pretreatment methods, for bringing continuous biosensing of inflammation closer to reality. Furthermore, collaborations between healthcare professionals and scientists, regulatory bodies, and biosensor engineers are needed for a successful translation of sensing technologies from the laboratory to clinical practice.</p