Terra incognita—cerebellar contributions to neuropsychiatric and cognitive dysfunction in behavioral variant frontotemporal dementia

Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioral variant frontotemporal dementia (bvFTD), a disease which is characterized by cognitive and neuropsychiatric deficits. The present study assessed whether degeneration in specific cerebellar subregions associate with indices of cognition and neuropsychiatric performance in bvFTD. Our results demonstrate a relationship between cognitive and neuropsychiatric decline across various domains of memory, language, emotion, executive, visuospatial function, and motivation and the degree of gray matter degeneration in cerebellar lobules V–VII. Most notably, bilateral cerebellar lobule VII and the posterior vermis emerged as distinct for memory processes, the right cerebellar hemisphere underpinned emotion, and the posterior vermis was highlighted in language dysfunction in bvFTD. Based on cortico-cerebellar connectivity maps, these findings in the cerebellum are consistent with the neural connections with the cortices involved in these domains in patients with bvFTD. Overall, the present study underscores the significance of cortical-cerebellar networks associated with cognition and neuropsychiatric dysfunction in bvFTD

A mixed methods study exploring organisational factors influencing the development of services for people with dementia in English hospices

Hospices are being challenged by changing demographics in the UK population. Originating from a response to cancer, hospices have struggled to diversify. As the population ages, dementia creates a particular challenge. A report by the Alzheimer’s Society predicts that one in three of us will die with or from it (Alzheimer's Society, n.d. i) making it difficult to see how hospices can avoid adapting their organisations to respond in some way. This research aims to understand hospices from an organisational perspective, considering what might be maintaining hospices in their current form and how they are responding to the changing environment in the context of dementia. The study hopes to contribute to discourse and knowledge around hospices as organisations and the use of institutional theory in practice. This mixed-method study takes an organisational perspective considering the hospice movement’s response to dementia and introduces theories such as organisational institutionalism and institutional work theory. The research provides a historical and interpretive analysis of the topic including a variety of literature and fieldwork collected from a survey, interviews and a focus group. The study highlights challenges of institutionalism such as legitimacy and how this impacts institutional change. Fieldwork indicated, despite significant barriers there was a real desire to support people with dementia. The study offers two models of institutionalism that might shed light on the challenges of change within the movement. The research concludes that despite some individual efforts, there is no viable model or coordinated attempt to shift the narrative of hospice care away from cancer towards dementia. The research offers some recommendations for consideration if the hospice movement wishes to respond to this population

Parenting, head injury and aggression: Predictive pathways of offending in male young offenders

Adolescence is a risk period for offending and head injury (HI), with rates of HI in young offender populations frequently exceeding those in the community. Poor parenting practices have been associated with increased risk of offending and development of reactive and proactive aggression. Preliminary research suggests HI may discriminate offender profiles within young offenders, but the influence of HI on offending alongside parenting and aggression is less well known. This study explored the relationships between parenting practices, reactive and proactive aggression, HI and offending in a sample of male young offenders from a Young Offender Institute (n=98) using self report data. A history of at least one HI was reported by 73.5%, with 61.1% reporting a knock out from their worst HI. Poor supervision emerged as a key predictor: predicting knock out history, indicators of offending and reactive and proactive aggression. Repeated HI was predictive of reactive aggression and a knock out history predicted earlier age of first offence. The impact of HI on outcomes via neuropsychological sequelea or as a “marker” for contextual risk factors such as poor supervision and reactive aggression are examined. Clinical implications for young offenders are discussed

Equilibrium binding energies from fluctuation theorems and force spectroscopy simulations

Brownian dynamics simulations are used to study the detachment of a particle from a substrate. Although the model is simple and generic, we attempt to map its energy, length and time scales onto a specific experimental system, namely a bead that is weakly bound to a cell and then removed by an optical tweezer. The external driving force arises from the combined optical tweezer and substrate potentials, and thermal fluctuations are taken into account by a Brownian force. The Jarzynski equality and Crooks' fluctuation theorem are applied to obtain the equilibrium free energy difference between the final and initial states. To this end, we sample non--equilibrium work trajectories for various tweezer pulling rates. We argue that this methodology should also be feasible experimentally for the envisioned system. Furthermore, we outline how the measurement of a whole free energy profile would allow the experimentalist to retrieve the unknown substrate potential by means of a suitable deconvolution. The influence of the pulling rate on the accuracy of the results is investigated, and umbrella sampling is used to obtain the equilibrium probability of particle escape for a variety of trap potentials.Comment: 21 pages, 11 figures, To appear in Soft Matte

Fronto-striatal atrophy in behavioural variant frontotemporal dementia & Alzheimer’s disease

Behavioral variant frontotemporal dementia (bvFTD) has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD). Considering the critical role the striatum has in cognition and behavior, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white-matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. In contrast, AD showed few frontostriatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal–ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms

Effects on Breathing of Agonists to μ-opioid or GABA\u3csub\u3eA\u3c/sub\u3e Receptors Dialyzed into the Ventral Respiratory Column of Awake and Sleeping Goats

Pulmonary ventilation (V̇I) in awake and sleeping goats does not change when antagonists to several excitatory G protein-coupled receptors are dialyzed unilaterally into the ventral respiratory column (VRC). Concomitant changes in excitatory neuromodulators in the effluent mock cerebral spinal fluid (mCSF) suggest neuromodulatory compensation. Herein, we studied neuromodulatory compensation during dialysis of agonists to inhibitory G protein-coupled or ionotropic receptors into the VRC. Microtubules were implanted into the VRC of goats for dialysis of mCSF mixed with agonists to either μ-opioid (DAMGO) or GABAA (muscimol) receptors. We found: (1) V̇I decreased during unilateral but increased during bilateral dialysis of DAMGO, (2) dialyses of DAMGO destabilized breathing, (3) unilateral dialysis of muscimol increased V̇I, and (4) dialysis of DAMGO decreased GABA in the effluent mCSF. We conclude: (1) neuromodulatory compensation can occur during altered inhibitory neuromodulator receptor activity, and (2) the mechanism of compensation differs between G protein-coupled excitatory and inhibitory receptors and between G protein-coupled and inotropic inhibitory receptors

Individual differences in the adoption and secure use of smart home technology

This developmental paper focuses on work that is currently being conducted to investigate individual differences in the adoption and secure use of smart home-based technologies by consumers. Specifically, the research focuses on individual differences in two primary psychological characteristics (risk taking propensity and impulsivity), technology adoption propensity, and a range of socio-demographic factors (including age, gender, and education level), to explore their potential influence on the adoption and secure use of smart home technologies at the consumer level. Through an online survey in December 2019-January 2020, 633 responses were collected from UK-based participants. These data will be discussed at the conference in order to understand the potential for further development and analysis of the data collected in relation to various theoretical perspectives, thus maximizing the potential theoretical contribution of the research across the management discipline

Influence of Mid-Latitude Cyclones on European Background Surface Ozone Investigated in Observations, MACC and MERRA-2 Reanalyses

The relationship between springtime mid-latitude cyclones and background ozone at two rural monitoring sites on the west coast of Europe -- Mace Head, Ireland and Monte Velho, Portugal -- is explored using a combination of observations and three reanalyses: 1) the European Centre for Medium-Range Weather Forecasts' (ECMWF) ERA-Interim reanalysis, 2) the Monitoring Atmospheric Composition and Climate (MACC) reanalysis and 3) NASA's Modern-Era Retrospective Analysis for Research and Applications Version-2 (MERRA-2) reanalysis. The ERA-Interim cyclone tracks are used here to establish the long-term relationship between cyclones and ozone observations (since 1988). The MACC reanalysis data set, which covers the period 2003-2012, is produced with the ECMWF integrated forecast system (IFS) model two-way coupled to a chemistry transport model (CTM). Since the MACC reanalysis uses a similar atmospheric model to ERA-Interim, MACC is used to explore the mechanisms within the case study cyclones that can influence surface ozone concentrations at Mace Head and Monte Velho. The MERRA-2 reanalysis also provides 3D distributions of ozone, although less ideal for analysis of surface ozone concentrations since MERRA-2 ozone under represents ozone variability outside the stratosphere as it does not have a detailed chemistry scheme or emission sources for the troposphere. The MERRA-2 reanalysis, which has the potential to identify more features within the cyclones as the resolution is higher than the MACC reanalysis, is used in conjunction with the MACC reanalysis to provide a measure of uncertainty to the case study analysis. We found the main source of high ozone to these two sites is from the stratosphere, which is well represented in both the MERRA-2 and the MACC reanalyses, either from direct injection into the cyclone or associated with aged airstreams from decaying downstream cyclones that can become entrained and descend toward the surface within new cyclones over the NA region