Plotting belonging : interrogating insider and outsider status in faith research

Fifteen years ago an outpouring of new academic material asserted the value of being an insider in religious research. Conventional assumptions that linked objectivity with outsider status were challenged. This valuable burst of scholarship worked hard to critique the kind of research that preceded it, where faith or identity was seen to compromise research values, and undermine integrity and rigour. This special edition interrogates the legacy of the shift towards practitioner-research with religious-spiritual-magical-secular communities, particularly, but not only, when research examines broader social, historical and political concerns as well as the processes of faith and belief. It examines some more experiential dynamics of research to consider how the insider/outsider debate plays out from the inside of the research process.Publisher PDFPeer reviewe

Plotting Belonging: Interrogating insider and outsider status in faith research

Fifteen years ago an outpouring of new academic material asserted the value of being an insider in religious research. Conventional assumptions that linked objectivity with outsider status were challenged. This valuable burst of scholarship worked hard to critique the kind of research that preceded it, where faith or identity was seen to compromise research values, and undermine integrity and rigour. This special edition interrogates the legacy of the shift towards practitioner-research with religious-spiritual-magical-secular communities, particularly, but not only, when research examines broader social, historical and political concerns as well as the processes of faith and belief. It examines some more experiential dynamics of research to consider how the insider/outsider debate plays out from the inside of the research proces

Hepatitis C Viral Dynamics Using a Combination Therapy of Interferon, Ribavirin, and Telaprevir: Mathematical Modeling and Model Validation

Groundbreaking new drugs called direct acting antivirals have been introduced recently for the treatment of chronic Hepatitis C virus infection. We introduce a mathematical model for Hepatitis C dynamics treated with the direct acting antiviral drug, telaprevir, alongside traditional interferon and ribavirin treatments to understand how this combination therapy affects the viral load of patients exhibiting different types of response. We use sensitivity and identifiability techniques to determine which model parameters can be best estimated from viral load data. Parameter estimation with these best estimable parameters is then performed to give patient-specific fits of the model to partial virologic response, sustained virologic response and breakthrough patients

Postnatal Changes in the Expression Pattern of the Imprinted Signalling Protein XLαs Underlie the Changing Phenotype of Deficient Mice

The alternatively spliced trimeric G-protein subunit XLαs, which is involved in cAMP signalling, is encoded by the Gnasxl transcript of the imprinted Gnas locus. XLαs deficient mice show neonatal feeding problems, leanness, inertia and a high mortality rate. Mutants that survive to weaning age develop into healthy and fertile adults, which remain lean despite elevated food intake. The adult metabolic phenotype can be attributed to increased energy expenditure, which appears to be caused by elevated sympathetic nervous system activity. To better understand the changing phenotype of Gnasxl deficient mice, we compared XLαs expression in neonatal versus adult tissues, analysed its co-localisation with neural markers and characterised changes in the nutrient-sensing mTOR1-S6K pathway in the hypothalamus. Using a newly generated conditional Gnasxl lacZ gene trap line and immunohistochemistry we identified various types of muscle, including smooth muscle cells of blood vessels, as the major peripheral sites of expression in neonates. Expression in all muscle tissues was silenced in adults. While Gnasxl expression in the central nervous system was also developmentally silenced in some midbrain nuclei, it was upregulated in the preoptic area, the medial amygdala, several hypothalamic nuclei (e.g. arcuate, dorsomedial, lateral and paraventricular nuclei) and the nucleus of the solitary tract. Furthermore, expression was detected in the ventral medulla as well as in motoneurons and a subset of sympathetic preganglionic neurons of the spinal cord. In the arcuate nucleus of Gnasxl-deficient mice we found reduced activity of the nutrient sensing mTOR1-S6K signalling pathway, which concurs with their metabolic status. The expression in these brain regions and the hypermetabolic phenotype of adult Gnasxl-deficient mice imply an inhibitory function of XLαs in energy expenditure and sympathetic outflow. By contrast, the neonatal phenotype of mutant mice appears to be due to a transient role of XLαs in muscle tissues

Investigation of SARS-CoV-2 faecal shedding in the community: a prospective household cohort study (COVID-LIV) in the UK

Background SARS-CoV-2 is frequently shed in the stool of patients hospitalised with COVID-19. The extent of faecal shedding of SARS-CoV-2 among individuals in the community, and its potential to contribute to spread of disease, is unknown. Methods In this prospective, observational cohort study among households in Liverpool, UK, participants underwent weekly nasal/throat swabbing to detect SARS-CoV-2 virus, over a 12-week period from enrolment starting July 2020. Participants that tested positive for SARS-CoV-2 were asked to provide a stool sample three and 14 days later. In addition, in October and November 2020, during a period of high community transmission, stool sampling was undertaken to determine the prevalence of SARS-CoV-2 faecal shedding among all study participants. SARS-CoV-2 RNA was detected using Real-Time PCR. Results A total of 434 participants from 176 households were enrolled. Eighteen participants (4.2%: 95% confidence interval [CI] 2.5–6.5%) tested positive for SARS-CoV-2 virus on nasal/throat swabs and of these, 3/17 (18%: 95% CI 4–43%) had SARS-CoV-2 detected in stool. Two of three participants demonstrated ongoing faecal shedding of SARS-CoV-2, without gastrointestinal symptoms, after testing negative for SARS-CoV-2 in respiratory samples. Among 165/434 participants without SARS-CoV-2 infection and who took part in the prevalence study, none had SARS-CoV-2 in stool. There was no demonstrable household transmission of SARS-CoV-2 among households containing a participant with faecal shedding. Conclusions Faecal shedding of SARS-CoV-2 occurred among community participants with confirmed SARS-CoV-2 infection. However, during a period of high community transmission, faecal shedding of SARS-CoV-2 was not detected among participants without SARS-CoV-2 infection. It is unlikely that the faecal-oral route plays a significant role in household and community transmission of SARS-CoV-2

The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for Cigarettes in Dependent and Occasional Cigarette Smokers

Background Dopaminergic functioning is thought to play critical roles in both motivation and addiction. There is preliminary evidence that dopamine agonists reduce the motivation for cigarettes in smokers. However, the effects of pramipexole, a dopamine D3 receptor preferring agonist, have not been investigated. The aim of this study was to examine the effects of an acute dose of pramipexole on the motivation to earn cigarettes and nondrug rewards. Methods Twenty dependent and 20 occasional smokers received 0.5 mg pramipexole using a double-blind, placebo-controlled crossover design. Motivation for cigarettes and consummatory nondrug rewards was measured using the DReaM-Choice task, in which participants earned, and later “consumed,” cigarettes, music, and chocolate. Demand for cigarettes was measured using the Cigarette Purchase Task (CPT). Self-reported craving, withdrawal, and drug effects were also recorded. Results Dependent smokers chose (p < .001) and button-pressed for (p < .001) cigarettes more, and chose chocolate less (p < .001), than occasional smokers. Pramipexole did not affect the number of choices for or amount of button-pressing for any reward including cigarettes, which was supported by a Bayesian analysis. The dependent smokers had greater demand for cigarettes than occasional smokers across all CPT outcomes (ps < .021), apart from elasticity. Pramipexole did not affect demand for cigarettes, and this was supported by Bayesian analyses. Pramipexole produced greater subjective “feel drug” and “dislike drug” effects than placebo. Conclusions Dependent and occasional cigarette smokers differed in their motivation for cigarettes but not for the nondrug rewards. Pramipexole did not acutely alter motivation for cigarettes. These findings question the role of dopamine D3 receptors in cigarette-seeking behavior in dependent and occasional smokers. Implications This study adds to the growing literature about cigarette versus nondrug reward processing in nicotine dependence and the role of dopamine in cigarette-seeking behavior. Our results suggest nicotine dependence is associated with a hypersensitivity to cigarette rewards but not a hyposensitivity to nondrug rewards. Furthermore, our results question the importance of dopamine D3 receptors in motivational processing of cigarettes in occasional and dependent smokers

Cardiometabolic thresholds for peak 30-min cadence and steps/day

PURPOSE: To provide empirically-supported thresholds for step-based intensity (i.e., peak 30-min cadence; average of the top 30 steps/min in a day) and steps/day in relation to cardiometabolic health outcomes. METHODS: Receiver operating characteristic curve analysis was applied to the National Health and Nutrition Examination Survey (NHANES) 2005-2006 accelerometer-derived step data to determine steps/day and peak 30-min cadence as risk screening values (i.e., thresholds) for fasting glucose, body mass index, waist circumference, high blood pressure, triglycerides, and HDL cholesterol. Thresholds for peak 30-min cadence and steps/day were derived that, when exceeded, classify the absence of each cardiometabolic risk factor. Additionally, logistic regression models that included the influence of age and smoking were developed using the sample weights, primary sampling units (PSUs), and stratification variables provided by the NHANES survey. Finally, a decision tree analysis was performed to delineate criteria for at-risk versus healthy populations using cadence bands. RESULTS: Peak 30-min cadence thresholds across cardiometabolic outcomes ranged from 66-72 steps/min. Steps/day thresholds ranged from 4325-6192 steps/day. Higher thresholds were observed in men compared to women. In men, higher steps/day thresholds were observed in age ranges of 30-39, while in women, higher thresholds were observed in the age-range 50-59 years. Decision trees for classifying being at low risk for metabolic syndrome contained one risk-free leaf at higher cadence bands, specifically for any time accumulated at ≥120 steps/min. CONCLUSIONS: Minimum thresholds representing absence of cardiometabolic risk range from 4325-6192 steps/day and 66-72 steps/min for peak 30-min cadence. Any time accumulated at ≥120 steps/min was associated with an absence of cardiometabolic risk. Although based on cross-sectional data, these thresholds represent potentially important and clinically interpretable daily physical activity goals

Prospective observational study of SARS-CoV-2 infection, transmission and immunity in a cohort of households in Liverpool City Region, UK (COVID-LIV): a study protocol

Introduction The emergence and rapid spread of COVID-19 have caused widespread and catastrophic public health and economic impact, requiring governments to restrict societal activity to reduce the spread of the disease. The role of household transmission in the population spread of SARS-CoV-2, and of host immunity in limiting transmission, is poorly understood. This paper describes a protocol for a prospective observational study of a cohort of households in Liverpool City Region, UK, which addresses the transmission of SARS-CoV-2 between household members and how immunological response to the infection changes over time.Methods and analysis Households in the Liverpool City Region, in which members have not previously tested positive for SARS-CoV-2 with a nucleic acid amplification test, are followed up for an initial period of 12 weeks. Participants are asked to provide weekly self-throat and nasal swabs and record their activity and presence of symptoms. Incidence of infection and household secondary attack rates of COVID-19 are measured. Transmission of SARS-CoV-2 will be investigated against a range of demographic and behavioural variables. Blood and faecal samples are collected at several time points to evaluate immune responses to SARS-CoV-2 infection and prevalence and risk factors for faecal shedding of SARS-CoV-2, respectively.Ethics and dissemination The study has received approval from the National Health Service Research Ethics Committee; REC Reference: 20/HRA/2297, IRAS Number: 283 464. Results will be disseminated through scientific conferences and peer-reviewed open access publications. A report of the findings will also be shared with participants. The study will quantify the scale and determinants of household transmission of SARS-CoV-2. Additionally, immunological responses before and during the different stages of infection will be analysed, adding to the understanding of the range of immunological response by infection severity