Adjusting for global effects in voxel-based morphometry: Gray matter decline in normal aging

AbstractResults from studies that have examined age-related changes in gray matter based on structural MRI scans have not always been consistent. Reasons for this variability likely include small or unevenly-distributed samples, different methods for tissue class segmentation and spatial normalization, and the use of different statistical models. Particularly relevant to the latter is the method of adjusting for global (total) gray matter when making inferences about regionally-specific changes. In the current study, we use voxel-based morphometry (VBM) to explore the impact of these methodological choices in assessing age-related changes in gray matter volume in a sample of 420 adults evenly distributed between the ages of 18–77years. At a broad level, we replicate previous findings, showing age-related gray matter decline in nearly all parts of the brain, with particularly rapid decline in inferior regions of frontal cortex (e.g., insula and left inferior frontal gyrus) and the central sulcus. Segmentation was improved by increasing the number of tissue classes and using less age-biased templates, and registration was improved by using a diffeomorphic flow-based algorithm (DARTEL) rather than a “constrained warp” approach. Importantly, different approaches to adjusting for global effects – not adjusting, Local Covariation, Global Scaling, and Local Scaling – significantly affected regionally-specific estimates of age-related decline, as demonstrated by ranking age effects across anatomical ROIs. Split-half cross-validation showed that, on average, Local Covariation explained a greater proportion of age-related variance across these ROIs than did Global Scaling. Nonetheless, the appropriate choice for global adjustment depends on one's assumptions and specific research questions. More generally, these results emphasize the importance of being explicit about the assumptions underlying key methodological choices made in VBM analyses and the inferences that follow

Automatic analysis (aa): efficient neuroimaging workflows and parallel processing using Matlab and XML.

Recent years have seen neuroimaging data sets becoming richer, with larger cohorts of participants, a greater variety of acquisition techniques, and increasingly complex analyses. These advances have made data analysis pipelines complicated to set up and run (increasing the risk of human error) and time consuming to execute (restricting what analyses are attempted). Here we present an open-source framework, automatic analysis (aa), to address these concerns. Human efficiency is increased by making code modular and reusable, and managing its execution with a processing engine that tracks what has been completed and what needs to be (re)done. Analysis is accelerated by optional parallel processing of independent tasks on cluster or cloud computing resources. A pipeline comprises a series of modules that each perform a specific task. The processing engine keeps track of the data, calculating a map of upstream and downstream dependencies for each module. Existing modules are available for many analysis tasks, such as SPM-based fMRI preprocessing, individual and group level statistics, voxel-based morphometry, tractography, and multi-voxel pattern analyses (MVPA). However, aa also allows for full customization, and encourages efficient management of code: new modules may be written with only a small code overhead. aa has been used by more than 50 researchers in hundreds of neuroimaging studies comprising thousands of subjects. It has been found to be robust, fast, and efficient, for simple-single subject studies up to multimodal pipelines on hundreds of subjects. It is attractive to both novice and experienced users. aa can reduce the amount of time neuroimaging laboratories spend performing analyses and reduce errors, expanding the range of scientific questions it is practical to address

Effect of laser irradiation on cell function and its implications in Raman spectroscopy

Lasers are instrumental in advanced bioimaging and Raman spectroscopy. However, they are also well known for their destructive effects on living organisms, leading to concerns about the adverse effects of laser technologies. To implement Raman spectroscopy for cell analysis and manipulation, such as Raman activated cell sorting, it is crucial to identify non-destructive conditions for living cells. Here, we evaluated quantitatively the effect of 532 nm laser irradiation on bacterial cell fate and growth at the single-cell level. Using a purpose-built microfluidic platform, we were able to quantify the growth characteristics i.e. specific growth rate and lag time of individual cells as well as the survival rate of a population in conjunction with Raman spectroscopy. Representative Gram-negative and Gram-positive species show a similar trend in response to laser irradiation dose. Laser irradiation could compromise physiological function of cells and the degree of destruction is both dose and strain dependent, ranging from reduced cell growth to a complete loss of cell metabolic activity and finally to physical disintegration. Gram-positive bacterial cells are more susceptible than Gram-negative bacterial strains to irradiation-induced damage. By directly correlating Raman acquisition with single cell growth characteristics, we provide evidence of non-destructive characteristics of Raman spectroscopy on individual bacterial cells. However, while strong Raman signals can be obtained without causing cell death, the variety of responses from different strains and from individual cells justify careful evaluation of Raman acquisition conditions if cell viability is critical

Optimising frontline learning and engagement between consultant-led neonatal teams in the West Midlands: a survey on the utility of an augmented simulation training technique

© The Authors. Published by BMC (Springer). This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/s41077-021-00181-1Background: In England neonatal care is delivered in operational delivery networks, comprising a combination of Neonatal Intensive Care(NICU), Local-Neonatal(LNU) or Special-Care Units (SCU), based on their ability to care for babies with different degrees of illness or prematurity. With the development of network care-pathways, the most premature and sickest are mostly triaged for delivery in services linked to NICU. This has created anxiety for teams in LNU and SCU. Less exposure to sicker babies has resulted in limited opportunities to maintain expertise for when these babies unexpectedly deliver at their centre and thereafter require transfer for care, to NICU. Simultaneously, LNU and SCU teams develop skills in care of the less ill and premature baby which would also be of benefit to NICU teams. A need for mutual learning through inter-unit multidirectional collaborative learning and engagement (hereafter also called neonatal networking) between teams of different designations emerged. Here neonatal networking is defined as collaboration, shared clinical learning and developing an understanding of local systems strengths and challenges between units of different and similar designations. We describe the responses to the development of a clinical and systems focused platform for this engagement between different teams within our neonatal ODN. Method: An interactive one-day programme was developed in the West Midlands, focusing on a non-hierarchical, equal partnership between neonatal teams from different unit designations. It utilised simulation around clinical scenarios, with a slant towards consultant engagement. Four groups rotating through four clinical simulation scenarios were developed. Each group participated in a clinical simulation scenario, led by a consultant and supported by nurses and doctors in training together with facilitators, with a further ~two consultants, as observers within the group. All were considered learners. Consultant candidates took turns to be participants and observers in the simulation scenarios so that at the end of the day all had led a scenario. Each simulation-clinical debrief session was lengthened by a further ~ 20 minutes, during which free style discussion with all learners occurred. This was to promote further bonding, through multidirectional sharing, and with a systems focus around understanding strengths and challenges of practices in different units. A consultant-focus was adopted to promote long-term engagement between units around shared care. There were four time points for this neonatal networking during the course of the day. Qualitative assessment and a Likert scale were used to assess this initiative over 4 years. Results: 155 individuals involved in frontline neonatal care participated. 77 were consultants, supported by neonatal trainees, staff grade doctors, clinical fellows, advanced neonatal nurse practitioners and nurses in training. All were invited to participate in the survey. The survey response rate was 80.6%. 79% felt that this learning strategy was highly relevant; 96% agreed that for consultants this was appropriate adult learning. 98% agreed that consultant training encompassed more than bedside clinical management, including forging communication links between teams. Thematic responses suggested that this was a highly useful method for multi-directional learning around shared care between neonatal unit. Conclusion: Simulation, enhanced with systems focused debrief, appeared to be an acceptable method of promoting multidirectional learning within neonatal teams of differing designations within the WMNODN

Crystal structure of vaccinia virus mRNA capping enzyme provides insights into the mechanism and evolution of the capping apparatus

[EN] Vaccinia virus capping enzyme is a heterodimer of D1 (844 aa) and D12 (287 aa) polypeptides that executes all three steps in m(7)GpppRNA synthesis. The D1 subunit comprises an N-terminal RNA triphosphatase (TPase)-guanylyltransferase (GTase) module and a C-terminal guanine-N7-methyltransferase (MTase) module. The D12 subunit binds and allosterically stimulates the MTase module. Crystal structures of the complete D1.D12 heterodimer disclose the TPase and GTase as members of the triphosphate tunnel metalloenzyme and covalent nucleotidyltransferase superfamilies, respectively, albeit with distinctive active site features. An extensive TPase-GTase interface clamps the GTase nucleotidyltransferase and OB-fold domains in a closed conformation around GTP. Mutagenesis confirms the importance of the TPase-GTase interface for GTase activity. The D1.D12 structure complements and rationalizes four decades of biochemical studies of this enzyme, which was the first capping enzyme to be purified and characterized, and provides new insights into the origins of the capping systems of other large DNA viruses.We are grateful for access to platforms of the Grenoble Partnership for Structural Biology, especially the High Throughput Crystallization (HTX) laboratory of the European Molecular Biology Laboratory (EMBL) for robotic crystallization. We thank the staff of the European Synchrotron Radiation Facility (ESRF)-EMBL Joint Structural Biology Group for help with data collection on beamlines BM14, ID14-4, ID14-3, and ID23-1. We acknowledge the help of Dr. Heinz Gut in setting up the cross-crystal averaging. This work was supported by National Institutes of Health grant GM42498 (to S.S.). S.S. is an American Cancer Society Research ProfessorKyrieleis, OJP.; Chang, J.; La Peña Del Rivero, MD.; Shuman, S.; Cusack, S. (2014). Crystal structure of vaccinia virus mRNA capping enzyme provides insights into the mechanism and evolution of the capping apparatus. Structure. 22(3):452-465. https://doi.org/10.1016/j.str.2013.12.014S45246522

Nudging towards COVID-19 and influenza vaccination uptake in medically at-risk children : EPIC study protocol of randomised controlled trials in Australian paediatric outpatient clinics

Introduction: Children with chronic medical diseases are at an unacceptable risk of hospitalisation and death from influenza and SARS-CoV-2 infections. Over the past two decades, behavioural scientists have learnt how to design non-coercive ‘nudge’ interventions to encourage positive health behaviours. Our study aims to evaluate the impact of multicomponent nudge interventions on the uptake of COVID-19 and influenza vaccines in medically at-risk children. Methods and analyses: Two separate randomised controlled trials (RCTs), each with 1038 children, will enrol a total of approximately 2076 children with chronic medical conditions who are attending tertiary hospitals in South Australia, Western Australia and Victoria. Participants will be randomly assigned (1:1) to the standard care or intervention group. The nudge intervention in each RCT will consist of three text message reminders with four behavioural nudges including (1) social norm messages, (2) different messengers through links to short educational videos from a paediatrician, medically at-risk child and parent and nurse, (3) a pledge to have their child or themselves vaccinated and (4) information salience through links to the current guidelines and vaccine safety information. The primary outcome is the proportion of medically at-risk children who receive at least one dose of vaccine within 3 months of randomisation. Logistic regression analysis will be performed to determine the effect of the intervention on the probability of vaccination uptake. Ethics and dissemination: The protocol and study documents have been reviewed and approved by the Women’s and Children’s Health Network Human Research Ethics Committee (HREC/22/WCHN/2022/00082). The results will be published via peer-reviewed journals and presented at scientific meetings and public forums. Trial registration number: NCT05613751

Harmful algal blooms and climate change: exploring future distribution changes

Harmful algae can cause death in fish, shellfish, marine mammals, and humans, via their toxins or from effects associated with their sheer quantity. There are many species, which cause a variety of problems around north-west Europe, and the frequency and distribution of algal blooms have altered in the recent past. Species distribution modelling was used to understand how harmful algal species may respond in the future to climate change, by considering environmental preferences and how these may shift. Most distribution studies to date use low resolution global model outputs. In this study, high resolution, downscaled shelf seas climate projections for the north-west European shelf were nested within lower resolution global projections, to understand how the distribution of harmful algae may change by the mid to end of century. Projections suggest that the habitat of most species (defined by temperature, salinity, depth, and stratification) will shift north this century, with suitability increasing in the central and northern North Sea. An increase in occurrence here might lead to more frequent detrimental blooms if wind, irradiance and nutrient levels are also suitable. Prioritizing monitoring of species in these susceptible areas could help in establishing early-warning systems for aquaculture and health protection schemes

Perceptual and conceptual processing of visual objects across the adult lifespan

Abstract: Making sense of the external world is vital for multiple domains of cognition, and so it is crucial that object recognition is maintained across the lifespan. We investigated age differences in perceptual and conceptual processing of visual objects in a population-derived sample of 85 healthy adults (24–87 years old) by relating measures of object processing to cognition across the lifespan. Magnetoencephalography (MEG) was recorded during a picture naming task to provide a direct measure of neural activity, that is not confounded by age-related vascular changes. Multiple linear regression was used to estimate neural responsivity for each individual, namely the capacity to represent visual or semantic information relating to the pictures. We find that the capacity to represent semantic information is linked to higher naming accuracy, a measure of task-specific performance. In mature adults, the capacity to represent semantic information also correlated with higher levels of fluid intelligence, reflecting domain-general performance. In contrast, the latency of visual processing did not relate to measures of cognition. These results indicate that neural responsivity measures relate to naming accuracy and fluid intelligence. We propose that maintaining neural responsivity in older age confers benefits in task-related and domain-general cognitive processes, supporting the brain maintenance view of healthy cognitive ageing

A systematic review of economic analyses of telehealth services using real time video communication

Background: Telehealth is the delivery of health care at a distance, using information and communication technology. The major rationales for its introduction have been to decrease costs, improve efficiency and increase access in health care delivery. This systematic review assesses the economic value of one type of telehealth delivery - synchronous or real time video communication - rather than examining a heterogeneous range of delivery modes as has been the case with previous reviews in this area. Methods A systematic search was undertaken for economic analyses of the clinical use of telehealth, ending in June 2009. Studies with patient outcome data and a non-telehealth comparator were included. Cost analyses, non-comparative studies and those where patient satisfaction was the only health outcome were excluded. Results 36 articles met the inclusion criteria. 22(61%) of the studies found telehealth to be less costly than the non-telehealth alternative, 11(31%) found greater costs and 3 (9%) gave the same or mixed results. 23 of the studies took the perspective of the health services, 12 were societal, and one was from the patient perspective. In three studies of telehealth to rural areas, the health services paid more for telehealth, but due to savings in patient travel, the societal perspective demonstrated cost savings. In regard to health outcomes, 12 (33%) of studies found improved health outcomes, 21 (58%) found outcomes were not significantly different, 2(6%) found that telehealth was less effective, and 1 (3%) found outcomes differed according to patient group. The organisational model of care was more important in determining the value of the service than the clinical discipline, the type of technology, or the date of the study. Conclusion Delivery of health services by real time video communication was cost-effective for home care and access to on-call hospital specialists, showed mixed results for rural service delivery, and was not cost-effective for local delivery of services between hospitals and primary care

Successful Blue Economy Examples With an Emphasis on International Perspectives

Careful definition and illustrative case studies are fundamental work in developing a Blue Economy. As blue research expands with the world increasingly understanding its importance, policy makers and research institutions worldwide concerned with ocean and coastal regions are demanding further and improved analysis of the Blue Economy. Particularly, in terms of the management connotation, data access, monitoring, and product development, countries are making decisions according to their own needs. As a consequence of this lack of consensus, further dialogue including this cases analysis of the blue economy is even more necessary. This paper consists of four chapters: (I) Understanding the concept of Blue Economy, (II) Defining Blue economy theoretical cases, (III) Introducing Blue economy application cases and (IV) Providing an outlook for the future. Chapters (II) and (III) summarizes all the case studies into nine aspects, each aiming to represent different aspects of the blue economy. This paper is a result of knowledge and experience collected from across the global ocean observing community, and is only made possible with encouragement, support and help of all members. Despite the blue economy being a relatively new concept, we have demonstrated our promising exploration in a number of areas. We put forward proposals for the development of the blue economy, including shouldering global responsibilities to protect marine ecological environment, strengthening international communication and sharing development achievements, and promoting the establishment of global blue partnerships. However, there is clearly much room for further development in terms of the scope and depth of our collective understanding and analysis