Healthcare Database and Research at Biostatistics Core Facility of John A. Burns School of Medicine

The Department of Quantitative Health Science at John A. Burns School of Medicine operates a Biostatistics Core Facility, which employs extensive healthcare databases to advance health-related research and enhance our understanding of healthcare. The Core Facility is dedicated to offering biostatistical research assistance to basic science, clinical, and translational researchers. Its expertise lies in the areas of study design, data management and analysis, grant proposal development, methodology research, and education in biostatistics and related fields

Untangling the dorsal diencephalic conduction system: a review of structure and function of the stria medullaris, habenula and fasciculus retroflexus

The often-overlooked dorsal diencephalic conduction system (DDCS) is a highly conserved pathway linking the basal forebrain and the monoaminergic brainstem. It consists of three key structures; the stria medullaris, the habenula and the fasciculus retrofexus. The frst component of the DDCS, the stria medullaris, is a discrete bilateral tract composed of fbers from the basal forebrain that terminate in the triangular eminence of the stalk of the pineal gland, known as the habenula. The habenula acts as a relay hub where incoming signals from the stria medullaris are processed and subsequently relayed to the midbrain and hindbrain monoaminergic nuclei through the fasciculus retrofexus. As a result of its wide-ranging connections, the DDCS has recently been implicated in a wide range of behaviors related to reward processing, aversion and motivation. As such, an understanding of the structure and connections of the DDCS may help illuminate the pathophysiology of neuropsychiatric disorders such as depression, addiction and pain. This is the frst review of all three components of the DDCS, the stria medullaris, the habenula and the fasciculus retrofexus, with particular focus on their anatomy, function and development

Virtual Dissection of White Matter Tracts in a Human brain using applied Game Design and Virtual Reality imaging

Visualisation of neural tracts in the human brain has previously been accomplished using two dimensional (2D) representational formats. In most cases, pre-operative visualisation is through the medium of 2D MRI image slices, representing coordinates in the brain through a combination of axial, sagittal, and coronal orthographic viewpoints. Software such as ExploreDTI can visualise off-axis viewpoints, however this method is limited to 2.5D image representations. The use of such 2D representations can require significant training in order to contextualise real-world 3D positions and accurately locate and identify neural tract pathways in the brain. Utilising anonymised tract data and advanced neuroimaging technologies pioneered by Trinity College Institute of Neuroscience (TCIN), the Technological University Dublin (TU Dublin) School of Media created an interactive visualisation environment using the Unity 3D game engine. This virtual reality visualisation utilises the Oculus Rift Virtual Reality (VR) peripheral to realise the first ever virtual dissection of the fornix in-vivo in a highly interactive full 3D environment. Ethical approval was granted by St James/Tallaght Research & Ethics Committee. MRI tract coordinate data in the form of .wrl format 3D objects were converted to game-engine ready formats such as .obj through a 3D editing program (3DS Max) then imported into Unity. A virtual representation of a human brain was created, and scale, position, and rotation manipulation of the VR environment implemented, using natural motion tracking and minimal button usage. Isolation of individual or groups of neural tracts was achieved using hand tracking and spatial selection. Positional data was mapped to MRI image planes in order to overlay traditional MRI images at each position to aid diagnostic accuracy. In summary, virtual dissection of the fornix pathway in the human brain, first individuated by TCIN was transcribed into a 3D VR gaming environment for spatially intuitive visualisation, manipulation, and analysis

Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli

Huntington's disease (HD), a genetic neurodegenerative disease caused by a polyglutamine expansion in the Huntingtin (Htt) protein, is accompanied by multiple mitochondrial alterations. Here, we show that mitochondrial fragmentation and cristae alterations characterize cellular models of HD and participate in their increased susceptibility to apoptosis. In HD cells, the increased basal activity of the phosphatase calcineurin dephosphorylates the pro-fission dynamin related protein 1 (Drp1), increasing its mitochondrial translocation and activation, and ultimately leading to fragmentation of the organelle. The fragmented HD mitochondria are characterized by cristae alterations that are aggravated by apoptotic stimulation. A genetic analysis indicates that correction of mitochondrial elongation is not sufficient to rescue the increased cytochrome c release and cell death observed in HD cells. Conversely, the increased apoptosis can be corrected by manoeuvres that prevent fission and cristae remodelling. In conclusion, the cristae remodelling of the fragmented HD mitochondria contributes to their hypersensitivity to apoptosis

The Relationship Between Ambulatory Arterial Stiffness Index and Blood Pressure Variability in Hypertensive Patients

Background and Objectives: Ambulatory arterial stiffness index (AASI) is well known as a predictor of cardiovascular mortality in hypertensive patients. Mathematically, AASI reflect the standard deviation (SD) of blood pressure (BP) variation. AASI is measured higher levels in non-dipper than dipper. Thus, AASI has a possibility of not only reflecting arterial stiffness but also BP variability and/or autonomic nervous dysfunction. Subjects and Methods: Consecutive data from 418 untreated hypertensive patients were analyzed retrospectively. We examined the association between the 24-hour ambulatory BP monitoring (ABPM) parameters and AASI. Results: AASI had a simple correlation with age (R=0.189, p<0.001), relative wall thickness (RWT) (R=0.115, p=0.019), left ventricular mass index (LVMI) (R=0.192, p<0.001), average systolic BP (SBP) (R=0.232, p<0.001), average pulse pressure (PP) (R=0.363, p<0.001), SD of diastolic BP (DBP) (R=-0.352,p<0.001), SD of PP (R=0.330, p<0.001), SD of heart rate (HR) (R=-0.268, p<0.001), and nocturnal dipping (R=-0.137, p=0.005). In multiple linear regression analysis model including clinical parameters and 24 hour-ABPM parameters, independent predictors of AASI were SD of PP (beta=1.246, p<0.001), SD of DBP (beta=-1.067, p<0.001), SD of SBP (beta=-0.197, p<0.001), and non-dipper (beta=0.054, p=0.033). Conclusion: AASI is closely correlated with BP variability. The result of this study shows that AASI is not only a parameter for arterial stiffness, but also a parameter for BP variability

Pre-hospital management protocols and perceived difficulty in diagnosing acute heart failure

Aim To illustrate the pre-hospital management arsenals and protocols in different EMS units, and to estimate the perceived difficulty of diagnosing suspected acute heart failure (AHF) compared with other common pre-hospital conditions. Methods and results A multinational survey included 104 emergency medical service (EMS) regions from 18 countries. Diagnostic and therapeutic arsenals related to AHF management were reported for each type of EMS unit. The prevalence and contents of management protocols for common medical conditions treated pre-hospitally was collected. The perceived difficulty of diagnosing AHF and other medical conditions by emergency medical dispatchers and EMS personnel was interrogated. Ultrasound devices and point-of-care testing were available in advanced life support and helicopter EMS units in fewer than 25% of EMS regions. AHF protocols were present in 80.8% of regions. Protocols for ST-elevation myocardial infarction, chest pain, and dyspnoea were present in 95.2, 80.8, and 76.0% of EMS regions, respectively. Protocolized diagnostic actions for AHF management included 12-lead electrocardiogram (92.1% of regions), ultrasound examination (16.0%), and point-of-care testings for troponin and BNP (6.0 and 3.5%). Therapeutic actions included supplementary oxygen (93.2%), non-invasive ventilation (80.7%), intravenous furosemide, opiates, nitroglycerine (69.0, 68.6, and 57.0%), and intubation 71.5%. Diagnosing suspected AHF was considered easy to moderate by EMS personnel and moderate to difficult by emergency medical dispatchers (without significant differences between de novo and decompensated heart failure). In both settings, diagnosis of suspected AHF was considered easier than pulmonary embolism and more difficult than ST-elevation myocardial infarction, asthma, and stroke. Conclusions The prevalence of AHF protocols is rather high but the contents seem to vary. Difficulty of diagnosing suspected AHF seems to be moderate compared with other pre-hospital conditions

Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats:mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour

AbstractModulation of metabotropic glutamate 2 (mGlu2) receptor function has huge potential for treating psychiatric and neurological diseases. Development of drugs acting on mGlu2 receptors depends on the development and use of translatable animal models of disease. We report here a stop codon mutation at cysteine 407 in Grm2 (cys407*) that is common in some Wistar rats. Therefore, researchers in this field need to be aware of strains with this mutation. Our genotypic survey found widespread prevalence of the mutation in commercial Wistar strains, particularly those known as Han Wistar. Such Han Wistar rats are ideal for research into the separate roles of mGlu2 and mGlu3 receptors in CNS function. Previous investigations, unknowingly using such mGlu2 receptor-lacking rats, provide insights into the role of mGlu2 receptors in behaviour. The Grm2 mutant rats, which dominate some selectively bred lines, display characteristics of altered emotionality, impulsivity and risk-related behaviours and increased voluntary alcohol intake compared with their mGlu2 receptor-competent counterparts. In addition, the data further emphasize the potential therapeutic role of mGlu2 receptors in psychiatric and neurological disease, and indicate novel methods of studying the role of mGlu2 and mGlu3 receptors

Development of “LvL UP 1.0”: a smartphone-based, conversational agent-delivered holistic lifestyle intervention for the prevention of non-communicable diseases and common mental disorders

BackgroundNon-communicable diseases (NCDs) and common mental disorders (CMDs) are the leading causes of death and disability worldwide. Lifestyle interventions via mobile apps and conversational agents present themselves as low-cost, scalable solutions to prevent these conditions. This paper describes the rationale for, and development of, “LvL UP 1.0″, a smartphone-based lifestyle intervention aimed at preventing NCDs and CMDs.Materials and MethodsA multidisciplinary team led the intervention design process of LvL UP 1.0, involving four phases: (i) preliminary research (stakeholder consultations, systematic market reviews), (ii) selecting intervention components and developing the conceptual model, (iii) whiteboarding and prototype design, and (iv) testing and refinement. The Multiphase Optimization Strategy and the UK Medical Research Council framework for developing and evaluating complex interventions were used to guide the intervention development.ResultsPreliminary research highlighted the importance of targeting holistic wellbeing (i.e., both physical and mental health). Accordingly, the first version of LvL UP features a scalable, smartphone-based, and conversational agent-delivered holistic lifestyle intervention built around three pillars: Move More (physical activity), Eat Well (nutrition and healthy eating), and Stress Less (emotional regulation and wellbeing). Intervention components include health literacy and psychoeducational coaching sessions, daily “Life Hacks” (healthy activity suggestions), breathing exercises, and journaling. In addition to the intervention components, formative research also stressed the need to introduce engagement-specific components to maximise uptake and long-term use. LvL UP includes a motivational interviewing and storytelling approach to deliver the coaching sessions, as well as progress feedback and gamification. Offline materials are also offered to allow users access to essential intervention content without needing a mobile device.ConclusionsThe development process of LvL UP 1.0 led to an evidence-based and user-informed smartphone-based intervention aimed at preventing NCDs and CMDs. LvL UP is designed to be a scalable, engaging, prevention-oriented, holistic intervention for adults at risk of NCDs and CMDs. A feasibility study, and subsequent optimisation and randomised-controlled trials are planned to further refine the intervention and establish effectiveness. The development process described here may prove helpful to other intervention developers

In situ observations of the Swiss periglacial environment using GNSS instruments

Monitoring of the periglacial environment is relevant for many disciplines including glaciology, natural hazard management, geomorphology, and geodesy. Since October 2022, Rock Glacier Velocity (RGV) is a new Essential Climate Variable (ECV) product within the Global Climate Observing System (GCOS). However, geodetic surveys at high elevation remain very challenging due to environmental and logistical reasons. During the past decades, the introduction of low-cost global navigation satellite system (GNSS) technologies has allowed us to increase the accuracy and frequency of the observations. Today, permanent GNSS instruments enable continuous surface displacement observations at millimetre accuracy with a sub-daily resolution. In this paper, we describe decennial time series of GNSS observables as well as accompanying meteorological data. The observations comprise 54 positions located on different periglacial landforms (rock glaciers, landslides, and steep rock walls) at altitudes ranging from 2304 to 4003 ma.s.l. and spread across the Swiss Alps. The primary data products consist of raw GNSS observables in RINEX format, inclinometers, and weather station data. Additionally, cleaned and aggregated time series of the primary data products are provided, including daily GNSS positions derived through two independent processing tool chains. The observations documented here extend beyond the dataset presented in the paper and are currently continued with the intention of long-term monitoring. An annual update of the dataset, available at https://doi.org/10.1594/PANGAEA.948334 (Beutel et al., 2022),​​​​​​​ is planned. With its future continuation, the dataset holds potential for advancing fundamental process understanding and for the development of applied methods in support of e.g. natural hazard management