The neuro-computational role of uncertainty in anxiety

Anxiety disorders are the most common mental health disorders and comprise a large number of years lost to disability. The work in this thesis is oriented towards understanding anxiety using a computational approach, focusing on uncertainty estimation as a key process. Chapter 1 introduces the role of uncertainty within anxiety and motivates the subsequent experimental chapters. Chapter 2 is a review of the computational role of the amygdala in humans, a key area for uncertainty computation. Chapter 3 is an experimental chapter which aimed to address gaps in the literature highlighted in the preceding chapters, namely the link between sensory uncertainty processing and anxiety and the role of the amygdala in this process. This chapter focuses on the development of a novel computational hierarchical Bayesian model to quantify sensory uncertainty and its application to neuroimaging data, with intolerance of uncertainty relating to greater neural activation in the insula but not amygdala. Chapter 4 targets the computational mechanisms underlying the negative self-bias observed in subclinical social anxiety. Again, this chapter focuses on the development of novel computational belief-update models which explicitly model uncertainty. Here, we see that a reduced trait self-positivity underpins this negative social evaluation process. The final experimental chapter presented in Chapter 5 investigates the link between different computational mechanisms, such as uncertainty, and a range of mood and anxiety symptomatology. This study revealed cognitive, social and somatic computational profiles that share a threat bias mechanism but have distinct negative-self bias and aversive learning signatures. Contrary to expectations, none of the uncertainty measures showed any associations with anxiety symptom subtypes. Finally, chapter 6 brings together the work in this thesis and alongside limitations of the work, discusses how these experiments contribute to our understanding of anxiety and the role of uncertainty across the anxiety spectrum

The impact of Forest School within Secondary School Education: an exploratory case study of Key Stage Three pupils’ views

In the UK, teaching within secondary schools almost always takes place within classrooms. Forest School offers one notable exception. However, this established learning approach often stops after Key Stage Two. This non-continuation is problematic given fears that successive generations are growing increasingly disconnected from nature and when one evaluates evidence of the benefits of Forest School. This thesis offers a case study exploring the impact of Forest School on Key Stage Three pupils. Through interviews and weekly journaling, twelve pupils’ views, perceptions, evaluations and reflections of a nine-week Forest School programme were collected and analysed. The Headteacher’s aspirations for Forest School were partly met as pupils evidenced how these sessions helped build their independence, confidence, ability to assess and take risks, and become more informed about nature. Furthermore, pupils also reported learning survival, social and physical skills, as well as enhancing their pro-environmental attitudes. One recurring theme within pupils’ reflections was how Forest School aided their mental and emotional wellbeing, a theme evident in the existing literature. This thesis is the first to assess the impact of Forest School through the experiences of Secondary School aged children. Given concerns regarding young people’s physical, mental and emotional well-being, and their growing disconnect from nature, this thesis’s exploratory findings suggest that Secondary School leaders may be missing an opportunity by omitting Forest School from curriculum enrichment activities. Whilst the Headteacher interview provides some explanation for this omission, future research could scope the will and capacity of secondary schools to facilitate Forest School. Moreover, researchers could test the impact of Forest School at Key Stage Four and/or undertake a longitudinal study following one cohort’s engagement in Forest School through the Five Key Stages. To gain greater traction from curriculum decision makers, Forest School leaders should continue better embedding cross-curricular learning gains through activities

On the X-ray properties of submm-selected galaxies

We present an analysis of the X-ray properties of 35 submm galaxies(SMGs) in the CDF-N. Using a sample of robust 850micron-selected galaxies, with accurate positions from Spitzer and/or radio counterparts, we find 16 objects (45+/-8%) with significant X-ray detections in the 2Ms Chandra data. 6 of these SMGs (~17+/-6%) have measured X-ray luminosities or upper limits consistent with those expected based on the far-infrared (FIR) or radio-derived star formation rate (SFR), and hence with the X-rays coming solely from star formation. In another 7 sources (20+/-7%) a dominant AGN contribution to the X-ray emission is required, while in 3 more it is unclear whether stellar process or accretion are responsible. Stacking of the X-ray undetected SMGs reveals a highly significant detection. If due to star formation, this corresponds to an average X-ray derived SFR of ~150 Msun/yr. We deduce that the AGN fraction in SMGs based on X-ray observations is 20-29 (+/-7) %, which is towards the lower limit of previous estimates. Spectral analysis shows that in general the SMGs are not heavily obscured in the X-ray but most of the SMGs classfied as AGN show absorption with N_H in excess of 10^22 cm^-2. Of the secure AGN, the bolometric luminosity appears to be dominated by the AGN in only 3 cases. In ~85% of the SMGs, the X-ray spectrum effectively rules out an AGN contribution that dominates the bolometric emission, even if the AGN is Compton thick. The evidence therefore suggests that intense star formation accounts for both the FIR and X-ray emission in most SMGs. We argue that, rather than having an especially high AGN fraction or duty cycle, SMGs have a high X-ray detection rate at very faint fluxes partly because of their high star formation rates and, in rarer cases, because the submm emission is from an AGN.(abridged)Comment: 12 pages, 5 figures, accepted for publication in MNRA

Clustering of Dust-Obscured Galaxies at z ~ 2

We present the angular autocorrelation function of 2603 dust-obscured galaxies (DOGs) in the Bootes field of the NOAO Deep Wide-Field Survey. DOGs are red, obscured galaxies, defined as having R-[24] \ge 14 (F_24/F_R \ga 1000). Spectroscopy indicates that they are located at 1.5 \la z \la 2.5. We find strong clustering, with r_0 = 7.40^{+1.27}_{-0.84} Mpc/h for the full F_24 > 0.3 mJy sample. The clustering and space density of the DOGs are consistent with those of submillimeter galaxies, suggestive of a connection between these populations. We find evidence for luminosity-dependent clustering, with the correlation length increasing to r_0 = 12.97^{+4.26}_{-2.64} Mpc/h for brighter (F_24 > 0.6 mJy) DOGs. Bright DOGs also reside in richer environments than fainter ones, suggesting these subsamples may not be drawn from the same parent population. The clustering amplitudes imply average halo masses of log M = 12.2^{+0.3}_{-0.2} Msun for the full DOG sample, rising to log M = 13.0^{+0.4}_{-0.3} Msun for brighter DOGs. In a biased structure formation scenario, the full DOG sample will, on average, evolve into ~ 3 L* present-day galaxies, whereas the most luminous DOGs may evolve into brightest cluster galaxies.Comment: ApJL in press; 4 pages, 3 figures, 1 tabl

Collecting genetic samples and linked mental health data from adolescents in schools:Protocol co-production and a mixed-methods pilot of feasibility and acceptability

OBJECTIVES: To coproduce a school-based protocol and examine acceptability and feasibility of collecting saliva samples for genetic studies from secondary/high school students for the purpose of mental health research. DESIGN: Protocol coproduction and mixed-methods feasibility pilot. SETTING: Secondary schools in Wales, UK. PARTICIPANTS: Students aged 11–13 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Coproduced research protocol including an interactive science workshop delivered in schools; school, parental and student recruitment rates; adherence to protocol and adverse events; ability to extract and genotype saliva samples; student enjoyment of the science workshop and qualitative analysis of teacher focus groups on acceptability and feasibility. RESULTS: Five secondary schools participated in the coproduction phase, and three of these took part in the research study (eligible sample n=868 students). Four further schools were subsequently approached, but none participated. Parental opt-in consent was received from 98 parents (11.3% eligible sample), three parents (0.3%) actively refused and responses were not received for 767 (88.4%) parents. We obtained saliva samples plus consent for data linkage for 79 students. Only one sample was of insufficient quality to be genotyped. The science workshop received positive feedback from students. Feedback from teachers showed that undertaking research like this in schools is viewed as acceptable in principle, potentially feasible, but that there are important procedural barriers to be overcome. Key recommendations include establishing close working relationships between the research team and school classroom staff, together with improved methods for communicating with and engaging parents. CONCLUSIONS: There are major challenges to undertaking large-scale genetic mental health research in secondary schools. Such research may be acceptable in principle, and in practice DNA collected from saliva in classrooms is of sufficient quality. However, key challenges that must be overcome include ensuring representative recruitment of schools and sufficient parental engagement where opt-in parental consent is required

Testing hypotheses about the harm that capitalism causes to the mind and brain: a theoretical framework for neuroscience research

In this paper, we will attempt to outline the key ideas of a theoretical framework for neuroscience research that reflects critically on the neoliberal capitalist context. We argue that neuroscience can and should illuminate the effects of neoliberal capitalism on the brains and minds of the population living under such socioeconomic systems. Firstly, we review the available empirical research indicating that the socio-economic environment is harmful to minds and brains. We, then, describe the effects of the capitalist context on neuroscience itself by presenting how it has been influenced historically. In order to set out a theoretical framework that can generate neuroscientific hypotheses with regards to the effects of the capitalist context on brains and minds, we suggest a categorization of the effects, namely deprivation, isolation and intersectional effects. We also argue in favor of a neurodiversity perspective [as opposed to the dominant model of conceptualizing neural (mal-)functioning] and for a perspective that takes into account brain plasticity and potential for change and adaptation. Lastly, we discuss the specific needs for future research as well as a frame for post-capitalist research

Shear-Selected Clusters From the Deep Lens Survey III: Masses from Weak Lensing

We present weak lensing mass estimates of seven shear-selected galaxy cluster candidates from the Deep Lens Survey. The clusters were previously identified as mass peaks in convergence maps of 8.6 sq. deg of R band imaging, and followed up with X-ray and spectroscopic confirmation, spanning a redshift range 0.19 - 0.68. Most clusters contained multiple X-ray peaks, yielding 17 total mass concentrations. In this paper, we constrain the masses of these X-ray sources with weak lensing, using photometric redshifts from the full set of BVRz' imaging to properly weight background galaxies according to their lensing distance ratios. We fit both NFW and singular isothermal sphere profiles, and find that the results are insensitive to the assumed profile. We also show that the results do not depend significantly on the assumed prior on the position of the mass peak, but that this may become an issue in future larger samples. The inferred velocity dispersions for the extended X-ray sources range from 250-800 km/s, with the exception of one source for which no lensing signal was found. This work further establishes shear selection as a viable technique for finding clusters, but also highlights some unresolved issues such as determination of the mass profile center without biasing the mass estimate, and fully accounting for line-of-sight projections. A follow-up paper will examine the mass-X-ray scaling relations of these clusters.Comment: Accepted for publication in ApJ, 27 pages, 4 figures. Some discussion and clarification added. Cluster centre offset added to Table

Large Observatory for x-ray Timing (LOFT-P): a Probe-class mission concept study

LOFT-P is a concept for a NASA Astrophysics Probe-Class (<$1B) X-ray timing mission, based on the LOFT concept originally proposed to ESAs M3 and M4 calls. LOFT-P requires very large collecting area (>6 m^2, >10x RXTE), high time resolution, good spectral resolution, broad-band spectral coverage (2-30 keV), highly flexible scheduling, and an ability to detect and respond promptly to time-critical targets of opportunity. It addresses science questions such as: What is the equation of state of ultra dense matter? What are the effects of strong gravity on matter spiraling into black holes? It would be optimized for sub-millisecond timing to study phenomena at the natural timescales of neutron star surfaces and black hole event horizons and to measure mass and spin of black holes. These measurements are synergistic to imaging and high-resolution spectroscopy instruments, addressing much smaller distance scales than are possible without very long baseline X-ray interferometry, and using complementary techniques to address the geometry and dynamics of emission regions. A sky monitor (2-50 keV) acts as a trigger for pointed observations, providing high duty cycle, high time resolution monitoring of the X-ray sky with ~20 times the sensitivity of the RXTE All-Sky Monitor, enabling multi-wavelength and multi-messenger studies. A probe-class mission concept would employ lightweight collimator technology and large-area solid-state detectors, technologies which have been recently greatly advanced during the ESA M3 study. Given the large community interested in LOFT (>800 supporters, the scientific productivity of this mission is expected to be very high, similar to or greater than RXTE (~2000 refereed publications). We describe the results of a study, recently completed by the MSFC Advanced Concepts Office, that demonstrates that LOFT-P is feasible within a NASA probe-class mission budget.Comment: Proc. SPIE 9905, Space Telescopes and Instrumentation 2016: Ultraviolet to Gamma Ray, 99054Y (July 18, 2016

CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study

Serological correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination ("vaccine breakthrough") have been described. However, T cell correlates of protection against breakthrough are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. Here, 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK cohort study were enrolled in a nested case-control study. Cases were those who tested SARS-CoV-2 PCR or lateral flow device (LFD) positive after two vaccine doses during the Delta-predominant era (n = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period (n = 247). Previous SARS-CoV-2 infection prior to vaccination was associated with reduced odds of vaccine breakthrough. Using samples from 28 d after the second vaccine dose, before all breakthroughs occurred, we observed future cases had lower ancestral spike (S)- and receptor binding domain-specific IgG titers and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls, although these differences did not persist when individuals were stratified according to previous infection status before vaccination. In a subset of matched infection-naïve cases and controls, vaccine breakthrough cases had lower CD4+ and CD8+ IFNγ and tumor necrosis factor (TNF) responses to Delta S peptides compared with controls. For CD8+ responses, this difference appeared to be driven by reduced responses to Delta compared with ancestral peptides among cases; this reduced response to Delta peptides was not observed in controls. Our findings support a protective role for T cells against Delta breakthrough infection. IMPORTANCE Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs vaccine policy for booster doses and future vaccine designs. Existing studies demonstrate humoral correlates of protection, but the role of T cells in protection is still unclear. In this study, we explore antibody and T cell immune responses associated with protection against Delta variant vaccine breakthrough infection in a well-characterized cohort of UK Healthcare Workers (HCWs). We demonstrate evidence to support a role for CD4+ and CD8+ T cells as well as antibodies against Delta vaccine breakthrough infection. In addition, our results suggest a potential role for cross-reactive T cells in vaccine breakthrough