We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Compulsive-like rigidity may be associated with hyposerotonergia and increased kynurenine (KYN) pathway activity. Conversion of tryptophan (TRP) to KYN, which may contribute to hyposerotonergia, is bolstered by inflammation and could be related to altered gut microbiota composition. Here, we studied these mechanisms in a naturalistic animal model of compulsive-like behavioural rigidity, that is, large nest building (LNB) in deer mice (Peromyscus sp.).
Methods:
Twenty-four (24) normal nest building (NNB) and 24 LNB mice (both sexes) were chronically administered either escitalopram (a selective serotonin reuptake inhibitor; 50 mg/kg/day) or a control solution, with nesting behaviour analysed before and after intervention. After endpoint euthanising, frontal cortices and striata were analysed for TRP and its metabolites, plasma for microbiota-derived lipopolysaccharide (LPS) and its binding protein (lipopolysaccharide binding protein), and stool samples for microbial DNA.
Results:
LNB, but not NNB, decreased after escitalopram exposure. At baseline, LNB was associated with reduced frontal cortical TRP concentrations and hyposerotonergia that was unrelated to altered KYN pathway activity. In LNB mice, escitalopram significantly increased frontal-cortical and striatal TRP without altering serotonin concentrations. Treated LNB, compared to untreated LNB and treated NNB mice, had significantly reduced plasma LPS as well as a microbiome showing a decreased inferred potential to synthesise short-chain fatty acids and degrade TRP.
Conclusions:
These findings support the role of altered serotonergic mechanisms, inflammatory processes, and gut microbiome involvement in compulsive-like behavioural rigidity. Our results also highlight the importance of gut-brain crosstalk mechanisms at the level of TRP metabolism in the spontaneous development of such behaviour.
This paper explores the intersection of physical health and recovery-oriented approaches in psychosis, offering a unique perspective through autoethnography. By combining personal experience with a broader analysis of existing mental health frameworks, the paper highlights the often overlooked importance of physical health in the recovery process for individuals with psychosis. The autoethnographic narrative reveals the complex challenges posed by antipsychotic medications, including weight gain and metabolic complications, and their impact on overall well-being. It emphasizes the dual stigma of mental health challenges and weight gain, highlighting the need for a more integrated, holistic approach to mental health care. Recommendations include enhanced education for healthcare providers, personalized care plans, and a multidisciplinary approach aimed at bridging the gap between physical and mental health in psychosis recovery.
The consent process for research studies can be burdensome for potential participants due to complex information and lengthy consent forms. This pragmatic study aimed to improve the consent experience and evaluate its impact on participant decision making, study knowledge, and satisfaction with the In Our DNA SC program, a population-based genomic screening initiative. We compared two consent procedures: standard consent (SC) involving a PDF document and enhanced consent (EC) incorporating a pictograph and true or false questions. Decision-making control, study knowledge, satisfaction, and time to consent were assessed. We analyzed data for 109 individuals who completed the SC and 96 who completed the EC. Results indicated strong decision-making control and high levels of knowledge and satisfaction in both groups. While no significant differences were found between the two groups, the EC experience took longer for participants to complete. Future modifications include incorporating video modules and launching a Spanish version of the consent experience. Overall, this study contributes to the growing literature on consent improvements and highlights the need to assess salient components and explore participant preferences for receiving consent information.
Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.
Aims
To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.
Method
We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.
Results
Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.
Conclusions
We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.
The ability to manipulate brain function through the communication between the microorganisms in the gastrointestinal tract and the brain along the gut-brain axis has emerged as a potential option to improve cognitive and emotional health. Dietary composition and patterns have demonstrated a robust capacity to modulate the microbiota-gut-brain axis. With their potential to possess pre-, pro-, post-, and synbiotic properties, dietary fibre and fermented foods stand out as potent shapers of the gut microbiota and subsequent signalling to the brain. Despite this potential, few studies have directly examined the mechanisms that might explain the beneficial action of dietary fibre and fermented foods on the microbiota-gut-brain axis, thus limiting insight and treatments for brain dysfunction. Herein, we evaluate the differential effects of dietary fibre and fermented foods from whole food sources on cognitive and emotional functioning. Potential mediating effects of dietary fibre and fermented foods on brain health via the microbiota-gut-brain axis are described. Although more multimodal research that combines psychological assessments and biological sampling to compare each food type is needed, the evidence accumulated to date suggests that dietary fibre, fermented foods, and/or their combination within a psychobiotic diet can be a cost-effective and convenient approach to improve cognitive and emotional functioning across the lifespan.
This chapter examines the international roles played by the Organization of African Unity (OAU)/ African Union (AU) during two global health crises. The two health crises included for study are the HIV/ Aids crisis, beginning in 1981, and the COVID-19 crisis that erupted in February 2020. Over the course of the Aids crisis, the AU was formally launched to replace the OAU in July 2002, following three years of planning. African leaders judged that the OAU had failed to live up to its promises, and they created a somewhat more ambitious ‘Constitutive Act’ to guide the activities of the AU. The response to the Aids crisis was one among the many areas in which the OAU failed to promote the welfare of African peoples.
Following the theoretical framing of this volume, this chapter attempts to identify the OAU or AU roles across two dimensions. It seeks to assess what roles the OAU/ AU adopted in relation to other major international organizations (IOs) and the ‘global order’ that prevailed in each health crisis (‘functional role’); and the roles that it adopted in dealing with the respective health crises (‘relationship role’). The evidence gathered here shows that the roles of the OAU/ AU with respect to its relational role demands changed substantially across the two crises.
The research design for this chapter entails establishing a baseline of role selection by the OAU before the advent of the Aids crises. This will enable us to perceive how roles changed in the face of two successive crises. When other, earlier issues were on its agenda, the OAU was performing strikingly different roles on the world stage and in the global community of IOs. Accordingly, the changing roles of the OAU/ AU in response to the two global health crises make an excellent case for close examination. This chapter relies upon the secondary literature for identifying and labeling the roles of the OAU in the pre-Aids era, and also after the onset of the Aids crisis. These roles are well-described, albeit without the use of role theory language, in the existing literature. Since the COVID-19 crisis is a more recent one, the chapter draws chiefly upon press releases of the AU and news reports about AU activity to assess the AU's role during this crisis.
OBJECTIVES/GOALS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern due to its increasing prevalence and association with type 2 diabetes mellitus. Non-invasive magnetic resonance-based biomarkers can aid in the monitoring of disease progression and identification of patients at risk for chronic liver disease. METHODS/STUDY POPULATION: Over 600 subjects will be recruited from the San Antonio Mexican American Family Study and from a second study, which consists of (i) T2DM patients diagnosed with either MASLD or metabolic dysfunction-associated steatohepatitis (MASH) or (ii) metabolically healthy controls. Hydrogen-1 MRS and diffusion-weighted MRI (DW-MRI) will be used to measure liver fat fraction and liver stiffness biomarkers, respectively. Several potential biomarkers of liver stiffness will be evaluated in vivo using the intravoxel incoherent motion (IVIM) model for DW-MRI. To further improve the diagnostic accuracy of patients with liver fibrosis, we will integrate MRI/MRS data with relevant clinical indicators of hepatic metabolism. Results will be compared to biopsy samples to evaluate the model’s diagnostic accuracy. RESULTS/ANTICIPATED RESULTS: Based on preliminary data, we predict that IVIM will be able to accurately diagnose hepatic fibrosis in patients with MASLD, allowing it to be implemented in clinics with high-field MRI units easily. Previous studies have shown correlations between IVIM estimates and fibrosis stages, however, none included additional clinical indicators of liver disease in their models. We have already found significant differences in metabolic measurements such as fasting plasma glucose and HbA1c levels. Additionally, the use of machine learning in developing these models has shown improvements in the ability to extract features from the data. The aim is to achieve high accuracy and robustness in the staging of liver fibrosis. DISCUSSION/SIGNIFICANCE: Over 100 million people in the US are affected by MASLD. Without treatment, it progresses from hepatic steatosis to MASH, fibrosis (liver stiffening), and ultimately to hepatic cirrhosis and hepatocellular carcinoma (HCC). Continued research efforts and clinical implementation of MRI and MRS are vital in combating the growing burden of MASLD.
An average of 1300 adults develop First Episode Psychosis (FEP) in Ireland each year. Early Intervention in Psychosis (EIP) is now widely accepted as best practice in the treatment of conditions such as schizophrenia. A local EIP programme was established in the Dublin South Central Mental Health Service in 2012.
Methods:
This is a cross-sectional study of service users presenting to the Dublin South Central Mental Health Service with FEP from 2016 to 2022 following the introduction of the EIP programme. We compared this to a previously published retrospective study of treatment as usual from 2002 to 2012.
Results:
Most service users in this study were male, single, unemployed and living with their partner or spouse across both time periods. Cognitive Behavioural Therapy for psychosis was provided to 12% (n = 8) of service users pre-EIP as compared to 52% (n = 30) post-programme introduction (p < 0.001), and 3% (n = 2) of service users engaged with behavioural family therapy pre-EIP as opposed to 15% (n = 9) after (p < 0.01). Rates of composite baseline physical healthcare monitoring improved significantly (p < 0.001).
Conclusion:
Exclusive allocation of multidisciplinary team staff to EIP leads to improved compliance with recommended guidelines, particularly CBT-p, formal family therapy and physical health monitoring.
This book addresses the UK's social, political and economic turbulence, exploring proliferating crises and conflicts, from social dissent through rentier capitalism to the looming climate catastrophe and how they have produced a deepening 'crisis of authority' that forms the terrain of the Battle for Britain.
Introduction: Studying the Legal in Legal Geography
Legal geography explores the interconnections between law and space, a field of study that relates law to context, while simultaneously revealing geography’s legal footprints. The rich interconnections between law and space, and the diverse ways that each co-inform and co-constitute the other are legal geography’s ‘core objects of inquiry’. In this chapter, we observe how this area of scholarship has evolved over nearly three decades, beginning in the mid-1990s, a generational confluence of law and geography that is neither a ‘sub-discipline of human geography nor […] an area of specialized legal scholarship’ but rather (or, at least) ‘a truly interdisciplinary intellectual project’.
As a discrete ‘intellectual project’, legal geography features several defining characteristics. Core to its mission is to emplace law and to bring law to landscape. Legal geography likewise takes a broad sweep of form: from grand theory to the ‘small’; from global observations of space, time and law to (sometimes very local) place-based case studies; and from explicit disciplinary articulation to an implied nuanced analysis. In the latter case, legal geography can play a significant, albeit often unacknowledged role in informing the scholarship.
Writing in 1994, the foundational legal geographer Nicholas Blomley quoted Lawrence Friedman and David Harvey, who each in turn (yet separately) recognised the limitations of their own disciplines. Friedman argued ‘law […] is too important to be left to lawyers’, while Harvey mirrored this sentiment word for word, noting that ‘geography is too important to be left to geographers’. Each gave voice to a gap that these two complementary disciplines had left lying on the field, a ‘hidden to plain sight’ lacuna of spatial relations where law fails to acknowledge the world it inhabits, and geographers ignore or undervalue how ‘social spaces, lived places, and landscapes are inscribed with legal significance’.
In writing this chapter, we acknowledge our own disciplinary perspective on legal geography. We are both lawyers, variously critical property and human rights theorists. In many ways, unlike the ‘progress report’ that David Delaney penned from 2015 to 2017, when he wrote across three sequential journal articles of legal geography’s evolution through a human geographer’s lens, our brief survey of the field is necessarily a legal interpretation. Rather than surmising what is the effect of law on geography, as Delaney ventures, we observe how geography has informed (and informs) the law.
Large stratovolcanoes in the Cascade Range have high equilibrium-line altitudes that support glaciers whose Holocene and latest Pleistocene advances are amenable to dating. Glacier advances produced datable stratigraphic sequences in lateral moraines, which complement dating of end moraines. New mapping of glacial deposits on Mount Rainier using LIDAR and field observations supports a single latest Pleistocene or early Holocene advance. Rainier R tephra overlies deposits from this advance and could be as old as >11.6 ka; the advance could be of Younger Dryas age. Radiocarbon ages on wood interbedded between tills in the lateral moraines of Nisqually, Carbon, and Emmons glaciers and the South Tahoma glacier forefield suggest glacier advances between 200 and 550 CE, correlative with the First Millennium Advance in western Canada, and during the Little Ice Age (LIA) beginning as early as 1300 CE.
These results resolve previous contradictory interpretations of Mount Rainier's glacial history and indicate that the original proposal of a single pre-Neoglacial cirque advance is correct, in contrast to a later interpretation of two advances of pre- and post-Younger Dryas age, respectively. Meanwhile, the occurrence of the pre-LIA Burroughs Mountain Advance, interpreted in previous work as occurring 3–2.5 ka, is questionable based on inherently ambiguous interpretations of tephra distribution.
The enhanced spatial and spectral resolution provided by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on the Mars Reconnaissance Orbiter (MRO) has led to the discovery of numerous hydrated silicate minerals on Mars, particularly in the ancient, cratered crust comprising the southern highlands. Phases recently identified using visible/near-infrared spectra include: smectite, chlorite, prehnite, high-charge phyllosilicates (illite or muscovite), the zeolite analcime, opaline silica, and serpentine. Some mineral assemblages represent the products of aqueous alteration at elevated temperatures. Geologic occurrences of these mineral assemblages are described using examples from west of the Isidis basin near the Nili Fossae and with reference to differences in implied temperature, fluid composition, and starting materials during alteration. The alteration minerals are not distributed homogeneously. Rather, certain craters host distinctive alteration assemblages: (1) prehnite-chloritesilica, (2) analcime-silica-Fe,Mg-smectite-chlorite, (3) chlorite-illite (muscovite), and (4) serpentine, which furthermore has been found in bedrock units. These assemblages contrast with the prevalence of solely Fe,Mg-smectites in most phyllosilicate-bearing terrains on Mars, and they represent materials altered at depth then exposed by cratering. Of the minerals found to date, prehnite provides the clearest evidence for subsurface, hydrothermal/metamorphic alteration, as it forms only under highly restricted conditions (T = 200–400°C). Multiple mechanisms exist for forming the other individual minerals; however, the most likely formation mechanisms for the characteristic mineralogic assemblages observed are, for (1) and (2), low-grade metamorphism or hydrothermal (<400°C) circulation of fluids in basalt; for (3), transformation of trioctahedral smectites to chlorite and dioctahedral smectites to illite during diagenesis; and for (4), low-grade metamorphism or hydrothermal (<400°C) circulation of fluids in ultramafic rocks. Evidence for high-grade metamorphism at elevated pressures or temperatures >400°C has not been found.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
The assortment of trillions of microorganisms resident along the human gastrointestinal tract, our gut microbiota, has co-evolved with us over thousands of years. It can influence a plethora of aspects of human physiology, including host metabolism, immunity and even brain function, cognition and behaviour across the lifespan. The gut microbiota and the brain can communicate with one another, directly and indirectly, through immune system modulation, tryptophan metabolism, vagus nerve activity, the enteric nervous system and bioactive microbial by-products, or metabolites produced by the gut microbiome. Indeed, the gut microbiota are responsible for a rich reservoir of novel metabolites and bioactive substances that can have pleiotropic functionalities for the host. Moreover, diet, an easily accessible and thus powerful interventional tool, can act as a modulator of gut-microbial composition and activity, impacting on host physiology. As such, nutrition is seen as one of the major modulators of the gut microbiota. Intriguingly, although psychiatric conditions often include a dietary aspect, much research investigating this link in clinical populations ignores this relationship, missing a key therapeutic avenue. This has led to the concept of nutritional psychiatry, where we can use food and supplements to support mental health and brain function. As a result, it is critical to consider emerging microbiome-targeted dietary approaches with the greatest potential to improve health outcomes in a psychiatric population.
We report on frequency doubling of high-energy, high repetition rate ns pulses from a cryogenically gas cooled multi-slab ytterbium-doped yttrium aluminum garnet laser system, Bivoj/DiPOLE, using a type-I phase matched lithium triborate crystal. We achieved conversion to 515 nm with energy of 95 J at repetition rate of 10 Hz and conversion efficiency of 79%. High conversion efficiency was achieved due to successful depolarization compensation of the fundamental input beam.
This book is a study of the critical history of space, and the ways in which a dominant property ideology has entrenched an exclusionary and profoundly alienating version of spatial ordering. It focuses on select periods in time, when the seemingly linear trajectory of enclosure momentarily wavers and alternate spatial paths briefly materialise, before 'disappearing' from plain sight. Using the forest as a thematic device, Cristy Clark and John Page explore the tensions that pervade our propertied relationships: between commodity and community, abstraction and context, and private enclosure and the public square.
The book draws on a range of case studies including the thirteenth century Forest Charter, Thomas More's 'Utopia', the Diggers' radical agrarianism, the Paris Commune's battle for the right to the city, and Australian forest protestors of the late twentieth and early twenty-first centuries. By analysing these movements and their contexts, Clark and Page illustrate the origin, history and legal status of the lawful forest and its modern-day companions. Although the dominant spatial paradigm is one where private rights prevail, this book shows that communal relationships with land have always been part of our law and culture.
As I argued in the previous chapter, conjunctural analysis is a spatio-temporal approach, exploring the particular configurations of time and place that make up a conjuncture. Somewhat artificially, I focused on the spatial dynamics and dimensions in the last chapter. Here I turn to the challenge of thinking about time. We can catch a glimpse of its complexity by considering the different stories that have been told about Brexit and the Battle for Britain. These narratives operate with different senses of time: some tell us about long histories (of decline or a fall from greatness); others offer fast-paced accounts of quickly moving events (stories of political calculation and manoeuvring). More rarely are these different senses of time brought together – as multiple temporalities (different orderings and experiences of time) that co-exist and interact. Felski, for example, has argued that time
is a concept of enormous complexity, including questions of measurement, rhythm, synchronization, sequence, tempo and intensity. It spans the personal and the public, work and leisure, the instantaneous and the eternal, intimate relations and global structures, everyday life and conditions of extremity. It exists at many different levels and is experienced in radically divergent ways. (2000: 16– 17)
Just as Chapter 1 argued that the space of the conjuncture is no simple matter (demanding thinking the nation transnationally), so this chapter will explore the multiple orderings and senses of time that are in play in the conjuncture. Thinking about temporalities, rather than time/times, is a way of trying to treat time as enmeshed in social, political-cultural and economic relations and processes and conflicts. Indeed, I will suggest, it is the intersections and entanglements of these different temporalities – the ways that they come to be condensed in the present – that gives the conjuncture its distinctive character. As a result, this chapter is organised around the notion of different temporalities. It will explore the different orderings of time that are associated with particular fields of relationships which have distinctive dynamics of crisis, contestations and (temporary) resolutions. These temporalities are, however, not entirely separate: each provides some of the conditions for the others and is affected in turn by their dynamics.