Investigating resting-state functional connectivity differences in cannabis use disorder and exploring their mitigation through brief mindfulness-based intervention

Cannabis Use Disorder (CUD) affects 22 million people globally and can lead to adverse psychosocial outcomes, including failed attempts to cut down/quit despite the experience of mental health and cognitive problems. Such problems have been (partly) ascribed to neurobiological alterations within pathways of the addiction neurocircuitry and high in cannabinoid receptors type 1 (CB1R), to which delta-9-tetrahydrocannabinol binds to exert its psychoactive effects. Emerging functional neuroimaging (fMRI) evidence show that cannabis users vs controls showed altered brain function while resting (i.e., without performing cognitively demanding tasks), measured via resting-state functional connectivity (rsFC); the evidence has not been synthesised systematically. Study 1 is a PROSPERO pre-registered systematic literature review of 21 studies examining rsFC differences between 737 cannabis users and 659 controls, and their associations with metrics of cannabis exposure and related problems. Cannabis users vs controls showed altered rsFC in fronto-frontal, frontostriatal, and fronto-temporal region pairings, and selected brain pathways correlated with cannabis exposure metrics. Methodological limitations precluded a detailed understanding of the nature of rsFC alterations. For example, it was unclear if rsFC changes were driven by dependent use/CUD, because no study had measured if cannabis users endorsed a CUD using current diagnostic tools (i.e., DSM-5). Furthermore, if rsFC alterations are specific to cannabis use was unclear due to inconsistent accounting for key demographics and substance use/mental health confounders entrenched with cannabis use known to affect brain function. Finally, the behavioural significance of rsFC alterations remained unclear, as it has seldom been examined in relation to cannabis exposure and related problems. Study 2 aimed to address the limitations of the literature, via examining 107 people aged 18-56 years (35 female) via fMRI scanning, socio-demographic, substance use, mental health, and cognitive testing. The primary aim was to compare rsFC between 65 individuals with a moderate-to-severe CUD who had tried to cut down or quit, and 42 controls, controlling for age, sex, alcohol and nicotine exposure, and depression symptom scores. Regions implicated in addiction neurocircuitry, dense in CB1R, and implicated in cognitive processes altered in cannabis users were selected as regions-of-interest (ROIs). Associations between CUD group rsFC changes and metrics of cannabis exposure and related problems were explored. People with a CUD vs controls showed greater rsFC between the following region pairings: nucleus accumbens (NAc)-frontal; pallidum-occipital/occipito-parietal, in correlation with CUD severity and cannabis use days/month; and putamen-occipito-parietal, in correlation with an earlier age of cannabis use onset; and lower hippocampus-occipital rsFC. Thus far, it is unclear if altered rsFC in CUD can be mitigated using psychological interventions. Study 3 examined if altered rsFC shown in the CUD group in Study 2 (n=56, aged 18-51 years), could be mitigated using one of the following ~2-week interventions: a mindfulness-based intervention (MBI, n=19), active placebo (relaxation; n=18), and passive placebo (daily monitoring; n=19). It used a double-blind, pseudo-randomised design based on age and sex. The primary aim was to examine intervention-group-by-time effects on rsFC in a priori ROIs with altered rsFC identified in Study 2 (i.e., NAc, putamen, pallidum, hippocampus), and how changes in rsFC correlated with those in cannabis exposure and related variables. Pre-to-post MBI, putamen-superior frontal gyrus (SFG)/frontal pole rsFC decreased; and hippocampus-anterior cingulate rsFC increased (correlated with more cannabis use days). Pre-to-post active placebo, putamen-frontal pole rsFC increased, correlated with decreased cannabis grams; putamen-SFG/cerebellum/brainstem rsFC increased; and pallidum-anterior superior temporal gyrus (aSTG) rsFC decreased. Pre-to-post passive placebo, putamen-frontal pole rsFC increased, correlated with less cannabis use days; pallidum-aSTG rsFC increased; and hippocampus-anterior cingulate and putamen-SFG/cerebellum/brainstem rsFC decreased. Findings from the thesis demonstrated rsFC alterations in cannabis users and confirmed existence of such alterations in CUD, and that alterations can be mitigated with a brief MBI, as well as relaxation and daily monitoring. rsFC alterations may reflect cannabis exposure or related problem (or both), or a neurobiological vulnerability predating the onset of cannabis use/CUD. Future fMRI studies with larger samples are required to confirm findings and to track over time if continuation of MBI, active and passive placebo interventions consolidate the effects reported herein. The results from this thesis expand upon neuroscientific theories of addiction validated in substances other than cannabis, by confirming partially overlapping alterations in CUD, and by showing that brief psychological interventions can target brain dysfunction in CUD

Earthquakes and sea-level change in Hokkaido, north-east Japan

This thesis details the results of an investigation into the pattern of relative sea-level (RSL) changes in north-east Hokkaido, Japan. The aim of the research is to better understand the importance of seismic and non-seismic processes in controlling spatial patterns of vertical land motions over a range of timescales. The main focus is on using salt-marsh sediments as a source of data to reconstruct RSL change during the current interseismic period, since c. 300 calibrated years before present (cal. yr BP). Previous research on the Pacific coast of Hokkaido suggests that this period is characterised by subsidence caused by strain accumulation on the locked part of the Pacific/North American plates. I apply foraminiferal-based methods of palaeoenvironmental reconstruction to develop, using transfer functions, quantitative reconstructions of RSL change at five sites in north-east Hokkaido. Contemporary foraminifera are zoned with respect to elevation and tidal inundation, and my preferred transfer function (a model that contains 87 samples and 24 taxa) has a prediction r2 of 0.75 and a root mean squared error of prediction of ± 0.32 m. I apply this transfer function to shallow fossil sediment sequences at five salt marshes and use a combination of 210Pb, 137Cs and tephra chronology to establish age models for the sequences. The reconstructions are consistent in demonstrating little net RSL change during the last 300-100 cal. yrs, with the exception of data from one site, Sarfutsu-toh, located on the northern tip of Hokkaido. Chronologies from two profiles developed on the Pacific coast record strong evidence for recent RSL rise since the mid-1980s, but during earlier periods of the 20th century reconstructed RSL was stable or falling. I compare my reconstructions with other direct and proxy records of land and sea-level motions. Previously published GPS and repeat levelling data indicates subsidence in south-east Hokkaido during the 20th century, although the spatial patterns and rates of change have varied. An unknown amount of this subsidence at the Kushiro tide gauge likely reflects anthropogenic activities associated with sediment compaction as well as mining-induced subsidence. An analysis of the tide-gauge records from Hokkaido show a more varied pattern of land motions, although they also confirm subsidence on the Pacific coast, close to the Kuril trench. A database of Holocene sea-level index points provides insights into longer-term millennial-scale trends in RSL. Data from six regions of Hokkaido demonstrate stable RSL close to present during the mid- and late Holocene; only the northern tip of Hokkaido (around Sarubetsu) is there evidence for a small mid-Holocene highstand of 1-3 m above present. Finally, a review of Pleistocene raised marine terrace data shows net uplift over the last c. 330 k yr, with two areas of particularly high uplift at Abashiri and on the Pacific coast near Kushiro. The evidence presented in this research demonstrates that it is incorrect to infer that the current interseismic period is characterised by subsidence. Overall, RSL has changed little in the last 300-100 cal. yrs. The subsidence recorded in the mid- and late 20th century on the Pacific coast of Hokkaido is not typical of the full interseismic period, nor can it have been sustained over Holocene or Pleistocene timescales. Limited data from previous earthquake cycles indicate that RSL was stable, rising or falling during previous interseismic intervals. These observations suggest that a representative ‘Hokkaido earthquake deformation cycle’ may not exist. Future research should better understand the controls of Quaternary volcanic activity on regional deformation patterns, and apply microfossil-based techniques to multiple earthquake cycles at sites to help define the spatial extent of land motions associated with different events

Importance of safety climate, teamwork climate and demographics: understanding nurses, allied health professionals and clerical staff perceptions of patient safety

Background: There is growing evidence regarding the importance of contextual factors for patient/staff outcomes and the likelihood of successfully implementing safety improvement interventions such as checklists; however, certain literature gaps still remain—for example, lack of research examining the interactive effects of safety constructs on outcomes. This study has addressed some of these gaps, together with adding to our understanding of how context influences safety. Purpose: The impact of staff perceptions of safety climate (ie, senior and supervisory leadership support for safety) and teamwork climate on a self-reported safety outcome (ie, overall perceptions of patient safety (PS)) were examined at a hospital in Southern Ontario. Methods: Cross-sectional survey data were collected from nurses, allied health professionals and unit clerks working on intensive care, general medicine, mental health or emergency department. Results: Hierarchical regression analyses showed that perceptions of senior leadership (p<0.001) and teamwork (p<0.001) were significantly associated with overall perceptions of PS. A non-significant association was found between perceptions of supervisory leadership and the outcome variable. However, when staff perceived poorer senior leadership support for safety, the positive effect of supervisory leadership on overall perceptions of PS became significantly stronger (p<0.05). Practice implications: Our results suggest that leadership support at one level (ie, supervisory) can substitute for the absence of leadership support for safety at another level (ie, senior level). While healthcare organisations should recruit into leadership roles and retain individuals who prioritise safety and possess adequate relational competencies, the field would now benefit from evidence regarding how to build leadership support for PS. Also, it is important to provide on-site workshops on topics (eg, conflict management) that can strengthen working relationships across professional and unit boundaries.York University Librarie

Climate-proofing a malaria eradication strategy

Two recent initiatives, the World Health Organization (WHO) Strategic Advisory Group on Malaria Eradication and the Lancet Commission on Malaria Eradication, have assessed the feasibility of achieving global malaria eradication and proposed strategies to achieve it. Both reports rely on a climate-driven model of malaria transmission to conclude that long-term trends in climate will assist eradication efforts overall and, consequently, neither prioritize strategies to manage the effects of climate variability and change on malaria programming. This review discusses the pathways via which climate affects malaria and reviews the suitability of climate-driven models of malaria transmission to inform long-term strategies such as an eradication programme. Climate can influence malaria directly, through transmission dynamics, or indirectly, through myriad pathways including the many socioeconomic factors that underpin malaria risk. These indirect effects are largely unpredictable and so are not included in climate-driven disease models. Such models have been effective at predicting transmission from weeks to months ahead. However, due to several well-documented limitations, climate projections cannot accurately predict the medium- or long-term effects of climate change on malaria, especially on local scales. Long-term climate trends are shifting disease patterns, but climate shocks (extreme weather and climate events) and variability from sub-seasonal to decadal timeframes have a much greater influence than trends and are also more easily integrated into control programmes. In light of these conclusions, a pragmatic approach is proposed to assessing and managing the effects of climate variability and change on long-term malaria risk and on programmes to control, eliminate and ultimately eradicate the disease. A range of practical measures are proposed to climate-proof a malaria eradication strategy, which can be implemented today and will ensure that climate variability and change do not derail progress towards eradication

Ultrasonic differentiation of healthy and cancerous neural tissue

It is well documented that intraoperative ultrasound offers improvements to the extent of tumour resected in neurosurgery but currently fails to depict the boundaries of more invasive tumours. Quantitative ultrasound (QUS) is a technique that models ultrasound scattering in tissue mathematically. It can act as a quantitative tool to identify cancerous regions and be used to define features which can train a machine learning (ML) classifier. The use of QUS to differentiate healthy and malignant brain tissue is the objective of this thesis. This work began with a proof of concept study which saw the effective implementation of QUS with a linear array transducer, at conventional frequencies, on phantom materials. The results were then used to train a K-nearest neighbours (KNN) binary classifier to differentiate between two soft tissues. Insight into the most practical parameters for near real time tissue identification was achieved, as well as the opportunity to produce parametric images for various QUS parameters. The effects of freezing and fixation of tissue on QUS results were also considered. The experimental design was developed to obtain a higher lateral spatial resolution before applying it to ex vivo human samples of ten healthy and eight high-grade glioma (HGG) tissues. This was accomplished with both a linear array and a single element scanning system, at centre frequencies of 25 and 74 MHz, respectively. The SoS and attenuation were found to be higher, on average, in the tumour samples than in the healthy tissue. The homodyned K-distribution (HK) parameters alone could distinguish between healthy and HGG tissue to 96% accuracy at 74 MHz, suggesting this is a viable solution for residual HGG detection. To explore the potential of ML with a larger data set, and to extend the study to low grade glioma (LGG) tissue, acoustic impedance maps based on 300 previously recorded microscope histology images of each tissue type were created. The interaction with high frequency (HF) ultrasound was explored using finite element analysis and QUS parameters were obtained. A classification algorithm was able to differentiate healthy and HGG to near perfect accuracy, but a significantly lower accuracy of 79% was found when distinguishing LGG from healthy tissue maps. This research represents a step forward in the otherwise unexplored landscape of HF QUS in brain tissue which necessitates further work to transition from laboratory based experiments to in vivo QUS to aid intraoperative glioma detection

Group Therapy for Eating Disorders: A Retrospective Case Study

An increasing amount of research supports group therapy as an effective treatment option for eating disorders (Moreno, 1994). In an attempt to further delineate therapeutic factors associated with productive group work, this study represents an exploratory, descriptive analysis of client and therapist perspectives on group process and outcome. Specifically, this retrospective study investigated what clients and their therapist considered important, helpful, and problematic in an aftercare group for hospitalized patients with eating disorders. The therapist and client perspectives were considered separately. These data were then classified into four categories: importance, benefits, problems, and critical incidents. A follow-up discussion explores similarities and differences between therapist and client perspectives. Implications for practice and research are presented

Group Therapy for Abused and Neglected Youth: Therapeutic and Child Advocacy Challenges

Although group therapy for abused and neglected youth is a viable and efficacious treatment option, facilitation is challenging. Group leaders must contain intense affect, manage multiple transferences, and advocate for their clients within the larger social welfare system. Using a case study of a group for sexually abused girls, this paper explores some of these issues and discusses ways in which therapists recognize and deal with the dual challenge of advocating for and treating children

Matching values and value in construction and design

In response to a series of influential government reports that have been critical of the approaches taken by, and outputs of, the UK construction industry, human aspects of construction have been given a new significance, particularly issues of value as judged by diverse stakeholders. This paper seeks to relate diverse and applied notions of value in construction with a similarly diverse body of knowledge contained within social and environmental psychology on values, from the work of Maslow and others in the 1950s and 1960s, to more recent contributions by Schwartz and colleagues. Collectively, the paper describes the work of an inter-disciplinary team with the active participation of key stakeholders in construction: professional organisations, practitioners, construction companies, clients and end product users, focused upon the search for a new 'language of value' that can aid the adoption of innovative conceptualisations of value within the industry. Finally, an innovative framework of value is presented that has been developed for design practitioners in the non-domestic building industry

UK rural land use archetypes

The Climate Change Committee (CCC) commissioned the UK Centre for Ecology and Hydrology to identify and characterise a set of baseline archetypes that are representative of current rural land-use and land-management in England and each of the devolved administrations. This work represents the first part of the CCC’s wider project on 'Archetypes for transforming rural UK land-use to high-carbon, climate resilient, nature rich and economically productive systems'. The report dated 29.06.2023 was published on the CCC website on 08.08.2023