Photon indistinguishability measurements under pulsed and continuous excitation

The indistinguishability of successively generated photons from a single quantum emitter is most commonly measured using two-photon interference at a beam splitter. Whilst for sources excited in the pulsed regime the measured bunching of photons reflects the full wavepacket indistinguishability of the emitted photons, for continuous wave (cw) excitation the inevitable dependence on detector timing resolution and driving strength obscures the underlying photon interference process. Here we derive a method to extract the photon indistinguishability from cw measurements by considering the relevant correlation functions. The equivalence of both methods is experimentally verified through comparison of cw and pulsed excitation of an archetypal source of photons, a single molecule

Beyond the Insider—Outsider Perspective: The Study of Religion as a Study of Discourse Construction

This essay reflects on contemporary theorizing of religion which embodies an explicit critique of the imperial project, seeing that by most common consent the scholarly disciplinary field of religious studies (history of religion, phenomenology of religion, Religionswissenschaft) is a late nineteenth century invention that coincides with the emergence of anthropology and ethnography as epiphenomena of the colonial project (whether as Orientalism or as exoticism the Other is rendered manageable subjects). The scholarly study of religion is, therefore, simultaneously a study of the history of theory and concept formation, and the social, cultural, and political work performed by such study and theorizing. The metatheory of the study of religion is a main focus of the essay. Alongside that, the essay focuses more pointedly on the concept of discourse, and considers the extraordinary situation where the same methodological vocabulary that functions in religious studies also functions in critical theological studies, which relativizes the division of ‘insider’ and ‘outsider’ perspectives. Yet both are conventionally practised either in isolation from each other as distinct theoretical and disciplinary bounded/defined study fields, or—the other and almost direct opposite—religious studies being performed in the context of theological study, situated in and offered by theological faculties. An overview of recent debates in the field of religious studies serves to highlight the continued struggle to demarcate the boundaries between the study of religion and the study of theology—in some of the recent, very strident debates mainstream religious studies is labelled as nothing more than theology. This contribution, then, aims at a kind of metatheoretical reflection on the study of religion and theology both as discourses that serve mythmaking, identity formation, culturally strategic purposes. That is, from the discourse perspective that is proposed here, it is possible to move beyond the definitional divide between religious studies and theology—even beyond ‘religion’ itself—to focus on the mundanely material practices that constitute that which is called religion. In the way in which the terms are used it is clear that the terminologies themselves bear the imprint of historical social discourses that occasioned the rise of their use. This essay, then, is something of a metacritique of the language of the study of religion—beyond religion, and beyond the study of religion and theology

Chronic psychosocial stressors are associated with alterations in salience processing and corticostriatal connectivity

Psychosocial stressors including childhood adversity, migration, and living in an urban environment, have been associated with several psychiatric disorders, including psychotic disorders. The neural and psychological mechanisms mediating this relationship remain unclear. In parallel, alterations in corticostriatal connectivity and abnormalities in the processing of salience, are seen in psychotic disorders. Aberrant functioning of these mechanisms secondary to chronic stress exposure, could help explain how common environmental exposures are associated with a diverse range of symptoms. In the current study, we recruited two groups of adults, one with a high degree of exposure to chronic psychosocial stressors (the exposed group, n = 20), and one with minimal exposure (the unexposed group, n = 22). All participants underwent a resting state MRI scan, completed the Aberrant Salience Inventory, and performed a behavioural task - the Salience Attribution Test (SAT). The exposed group showed reduced explicit adaptive salience scores (cohen's d = 0.69, p = 0.03) and increased aberrant salience inventory scores (d = 0.65, p = 0.04). The exposed group also showed increased corticostriatal connectivity between the ventral striatum and brain regions previously implicated in salience processing. Corticostriatal connectivity in these regions negatively correlated with SAT explicit adaptive salience (r = -0.48, p = 0.001), and positively correlated with aberrant salience inventory scores (r = 0.42, p = 0.006). Furthermore, in a mediation analysis there was tentative evidence that differences in striato-cortical connectivity mediated the group differences in salience scores

Dopaminergic organization of striatum is linked to cortical activity and brain expression of genes associated with psychiatric illness

Dopamine signaling is constrained to discrete tracts yet has brain-wide effects on neural activity. The nature of this relationship between local dopamine signaling and brain-wide neuronal activity is not clearly defined and has relevance for neuropsychiatric illnesses where abnormalities of cortical activity and dopamine signaling coexist. Using simultaneous PET-MRI in healthy volunteers, we find strong evidence that patterns of striatal dopamine signaling and cortical blood flow (an index of local neural activity) contain shared information. This shared information links amphetamine-induced changes in gradients of striatal dopamine receptor availability to changes in brain-wide blood flow and is informed by spatial patterns of gene expression enriched for genes implicated in schizophrenia, bipolar disorder, and autism spectrum disorder. These results advance our knowledge of the relationship between cortical function and striatal dopamine, with relevance for understanding pathophysiology and treatment of diseases in which simultaneous aberrations of these systems exist

The Topography of Striatal Dopamine and Symptoms in Psychosis: An Integrative PET and MRI study

Background: Striatal dopamine dysfunction is thought to underlie symptoms in psychosis, yet it remains unclear how a single neurotransmitter could cause the diverse presentations that are observed clinically. One hypothesis is that the consequences of aberrant dopamine signalling vary depending on where within the striatum the dysfunction occurs. Positron emission tomography (PET) allows for the quantification of dopamine function across the striatum. In the current study we use a novel method to investigate the relationship between spatial variability in dopamine synthesis capacity and psychotic symptoms. Methods: We used a multimodal imaging approach combining 18F-DOPA PET and resting state MRI in 29 patients with first episode psychosis and 21 healthy controls. In each participant, resting state functional connectivity maps were used to quantify the functional connectivity of each striatal voxel to well-established cortical networks. Network-specific striatal dopamine synthesis capacity(Kicer) was then calculated for the resulting connectivity defined parcellations. Results: The connectivity defined parcellations generated Kicer values with equivalent reliability, and significantly greater orthogonality to standard anatomical parcellation methods. As a result, dopamine-symptom associations were significantly different from one another for different subdivisions, whereas no unique subdivision relationships were found when using an anatomical parcellation. In particular, dopamine function within striatal areas connected to the default mode network was strongly associated with negative symptoms(p<0.001). Conclusion: These findings suggest that individual differences in the topography of dopamine dysfunction within the striatum contribute to shaping psychotic symptomatology. Further validation of the novel approach in future studies is necessary

Mesolimbic Dopamine Function Is Related to Salience Network Connectivity: An Integrative Positron Emission Tomography and Magnetic Resonance Study

BACKGROUND: A wide range of neuropsychiatric disorders, from schizophrenia to drug addiction, involve abnormalities in both the mesolimbic dopamine system and the cortical salience network. Both systems play a key role in the detection of behaviorally relevant environmental stimuli. Although anatomical overlap exists, the functional relationship between these systems remains unknown. Preclinical research has suggested that the firing of mesolimbic dopamine neurons may activate nodes of the salience network, but in vivo human research is required given the species-specific nature of this network. METHODS: We employed positron emission tomography to measure both dopamine release capacity (using the D2/3 receptor ligand 11C-PHNO, n = 23) and dopamine synthesis capacity (using 18F-DOPA, n = 21) within the ventral striatum. Resting-state functional magnetic resonance imaging was also undertaken in the same individuals to investigate salience network functional connectivity. A graph theoretical approach was used to characterize the relationship between dopamine measures and network connectivity. RESULTS: Dopamine synthesis capacity was associated with greater salience network connectivity, and this relationship was particularly apparent for brain regions that act as information-processing hubs. In contrast, dopamine release capacity was associated with weaker salience network connectivity. There was no relationship between dopamine measures and visual and sensorimotor networks, indicating specificity of the findings. CONCLUSIONS: Our findings demonstrate a close relationship between the salience network and mesolimbic dopamine system, and they are relevant to neuropsychiatric illnesses in which aberrant functioning of both systems has been observed

Effect of polygenic risk for schizophrenia on cardiac structure and function: a UK Biobank observational study

BACKGROUND: Cardiovascular disease is a major cause of excess mortality in people with schizophrenia. Several factors are responsible, including lifestyle and metabolic effects of antipsychotics. However, variations in cardiac structure and function are seen in people with schizophrenia in the absence of cardiovascular disease risk factors and after accounting for lifestyle and medication. Therefore, we aimed to explore whether shared genetic causes contribute to these cardiac variations. METHODS: For this observational study, we used data from the UK Biobank and included White British or Irish individuals without diagnosed schizophrenia with variable polygenic risk scores for the condition. To test the association between polygenic risk score for schizophrenia and cardiac phenotype, we used principal component analysis and regression. Robust regression was then used to explore the association between the polygenic risk score for schizophrenia and individual cardiac phenotypes. We repeated analyses with fibro-inflammatory pathway-specific polygenic risk scores for schizophrenia. Last, we investigated genome-wide sharing of common variants between schizophrenia and cardiac phenotypes using linkage disequilibrium score regression. The primary outcome was principal component regression. FINDINGS: Of 33 353 individuals recruited, 32 279 participants had complete cardiac MRI data and were included in the analysis, of whom 16 625 (51·5%) were female and 15 654 (48·5%) were male. 1074 participants were excluded on the basis of incomplete cardiac MRI data (for all phenotypes). A model regressing polygenic risk scores for schizophrenia onto the first five cardiac principal components of the principal components analysis was significant (F=5·09; p=0·00012). Principal component 1 captured a pattern of increased cardiac volumes, increased absolute peak diastolic strain rates, and reduced ejection fractions; polygenic risk scores for schizophrenia and principal component 1 were negatively associated (β=-0·01 [SE 0·003]; p=0·017). Similar to the principal component analysis results, for individual cardiac phenotypes, we observed negative associations between polygenic risk scores for schizophrenia and indexed right ventricular end-systolic volume (β=-0·14 [0·04]; p=0·0013, pFDR=0·015), indexed right ventricular end-diastolic volume (β=-0·17 [0·08]); p=0·025; pFDR=0·082), and absolute longitudinal peak diastolic strain rates (β=-0·01 [0·003]; p=0·0024, pFDR=0·015), and a positive association between polygenic risk scores for schizophrenia and right ventricular ejection fraction (β=0·09 [0·03]; p=0·0041, pFDR=0·015). Models examining the transforming growth factor-β (TGF-β)-specific and acute inflammation-specific polygenic risk scores for schizophrenia found significant associations with the first five principal components (F=2·62, p=0·022; F=2·54, p=0·026). Using linkage disequilibrium score regression, we observed genetic overlap with schizophrenia for right ventricular end-systolic volume and right ventricular ejection fraction (p=0·0090, p=0·0077). INTERPRETATION: High polygenic risk scores for schizophrenia are associated with decreased cardiac volumes, increased ejection fractions, and decreased absolute peak diastolic strain rates. TGF-β and inflammatory pathways might be implicated, and there is evidence of genetic overlap for some cardiac phenotypes. Reduced absolute peak diastolic strain rates indicate increased myocardial stiffness and diastolic dysfunction, which increases risk of cardiac disease. Thus, genetic risk for schizophrenia is associated with cardiac structural changes that can worsen cardiac outcomes. Further work is required to determine whether these associations are specific to schizophrenia or are also seen in other psychiatric conditions. FUNDING: National Institute for Health Research, Maudsley Charity, Wellcome Trust, Medical Research Council, Academy of Medical Sciences, Edmond J Safra Foundation, British Heart Foundation

Prion protein-specific antibodies that detect multiple TSE agents with high sensitivity

This paper describes the generation, characterisation and potential applications of a panel of novel anti-prion protein monoclonal antibodies (mAbs). The mAbs were generated by immunising PRNP null mice, using a variety of regimes, with a truncated form of recombinant ovine prion protein spanning residues 94–233. Epitopes of specific antibodies were mapped using solid-phase Pepscan analysis and clustered to four distinct regions within the PrP molecule. We have demonstrated the utility of these antibodies by use of Western blotting and immunohistochemistry in tissues from a range of different species affected by transmissible spongiform encephalopathy (TSE). In comparative tests against extensively-used and widely-published, commercially available antibodies, similar or improved results can be obtained using these new mAbs, specifically in terms of sensitivity of detection. Since many of these antibodies recognise native PrPC, they could also be applied to a broad range of immunoassays such as flow cytometry, DELFIA analysis or immunoprecipitation. We are using these reagents to increase our understanding of TSE pathogenesis and for use in potential diagnostic screening assays

Community environmental satisfaction: its forms and impact on migrants' happiness in urban China

BACKGROUND: The great number of internal migrants has become an important part of China's urban population. Improving migrants' well-being is emerging as a key to the state policy emphasized in China's New-type Urbanization Plan. Previous studies on subjective well-being (SWB) have primarily focused on the impacts of objective measures of community environment and consider migrants as a homogeneous group. This study extends the literature by exploring the impacts of perceived community environment on migrants' SWB and incorporating cohort differences in the analysis. METHODS: We use the 2015 national scale data-China Household Financial Survey (CHFS) data-to analyse the different forms of community environmental satisfaction and their impacts on migrants' subjective well-being. A total of 12,607 migrants were sampled from 29 of mainland China's 31 provinces. Latent class analysis is applied to explore the potential forms of community environmental satisfaction; multinomial and ordinal logistic regression models are constructed to examine the sociodemographic characteristics of different forms of community environmental satisfaction and the association between community environmental satisfaction and subjective well-being among migrant cohorts in urban China. RESULTS: Latent class analysis defines four distinctive latent classes, which mirror four different domains of migrants' perception of their local environments. They are called 'unsatisfying local environment', 'satisfying social environment', 'satisfying physical environment', and 'satisfying social life'. Results from the multinomial logistic regression model reveals that the four forms of community environmental satisfaction are underpinned by distinct sociodemographic characteristics. Results from a series of ordinal logistic regression models show that different forms of community environmental satisfaction, in particular satisfaction with the physical environment and with social life, are positively associated with migrants' happiness. The model results also suggest that cohort differences do exist among migrants. The positive effect of a satisfying physical environment on happiness tends to be greater in younger cohorts, while the positive effect of a satisfying social life on SWB is more observable in older cohorts. CONCLUSION: Satisfaction with community environment has a salient impact on urban Chinese migrants' happiness. For their SWB, improving migrants' physical living environments and social lives is relatively more important than social environment, which in a way mirrors migrants' current status with its deficiencies in terms of a comfortable living environment and social life. Moreover, there exist cohort differences that should be considered when making policies to enhance migrants' subjective well-being