Short-period line profile and light variations in the Beta Cephei star 19 Monocerotis

We present an analysis of 555 high-dispersion echelle spectra of 19 Mon obtained from two sites as well as 115 Strömgren uvby observations. We show that three periodicities are present at 5.229 94, 0.170 19 and 4.889 56 cycle d−1. The first periodicity has by far the largest amplitude. Photometric amplitude ratios and phase differences indicate an ℓ=2 mode, while the line profile variations unequivocally point to ℓ=2,m=-2. Because of the low amplitudes of the other two modes, very little can be said concerning them. Although 19 Mon was originally selected on the basis of its classification as a marginal Be star, the Be nature of the star is not supported by our observation

Sufism and Liberation across the Indo-Afghan Border: 1880-1928

How do we understand links between sufism and pro-egalitarian revolutionary activism in the early twentieth century; and how did upland compositions of self and community help constitute revolutionary activism in South Asia more broadly? Using Pashto poetry as my archive I integrate a history of radical egalitarian thought and political practice to a holistic study of self-making; of imperial spatiality; and of shifting gradients of power in the regions between Kabul and Punjab. Amid a chaotic rise of new practices of imperial and monarchic hegemony around the turn of the twentieth century, I argue, older sedimentations of ‘devotee selfhood’ in the high valleys of eastern Afghanistan gave rise, in social spaces preserved by self-reflexive poetic practice and circulation, to conscious desires for avoidance of all forms of hierarchy or sovereignty, in favour of a horizontal politics of reciprocity. Such inchoate drives for freedom later played a role in constituting anti-statist revolutionary subjectivities across great geographical and social distance. From upland sufi roots they rippled outward to intersect with the work of transnational socialist and anti-imperialist militants in Indian nationalist circles too; and even influenced scholars at the heart of the nascent Afghan nation-state

Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies

Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan–Meier estimator. Results: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R2 0.072; C3d: adjusted R2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1q−) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1q−) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30–1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3d−); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3d−) years; HR 0.38; 95% CI 0.15–0.97; p = 0.04]. Conclusion: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction

Using equity premium survey data to estimate future wealth

We present the first systematic methods for combining different experts' responses to equity premium surveys. These techniques are based on the observation that the survey data are approximately gamma distributed. This distribution has convenient analytical properties that enable us to address three important problems that investment managers must face. First, we construct probability density functions for the future values of equity index tracker funds. Second, we calculate unbiased and minimum least square error estimators of the future value of these funds. Third, we derive optimal asset allocation weights between equities and the risk-free asset for risk-averse investors. Our analysis allows for both herding and biasedness in expert responses. We show that, unless investors are highly uncertain about expert biases or forecasts are very highly correlated, many investment decisions can be based solely on the mean of the survey data minus any expected bias. We also make recommendations for the design of future equity premium surveys

Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

VEGFC reduces glomerular albumin permeability and protects against alterations in VEGF receptor expression in diabetic nephropathy

Elevated levels of vascular endothelial growth factor (VEGF) A are thought to cause glomerular endothelial cell (GEnC) dysfunction and albuminuria in diabetic nephropathy. We hypothesized that VEGFC could counteract these effects of VEGFA to protect the glomerular filtration barrier and reduce albuminuria. Isolated glomeruli were stimulated ex vivo with VEGFC, which reduced VEGFA- and type 2 diabetes–induced glomerular albumin solute permeability (Ps’alb). VEGFC had no detrimental effect on glomerular function in vivo when overexpression was induced locally in podocytes (podVEGFC) in otherwise healthy mice. Further, these mice had reduced glomerular VEGFA mRNA expression, yet increased glomerular VEGF receptor heterodimerization, indicating differential signaling by VEGFC. In a model of type 1 diabetes, the induction of podVEGFC overexpression reduced the development of hypertrophy, albuminuria, loss of GEnC fenestrations and protected against altered VEGF receptor expression. In addition, VEGFC protected against raised Ps’alb by endothelial glycocalyx disruption in glomeruli. In summary, VEGFC reduced the development of diabetic nephropathy, prevented VEGF receptor alterations in the diabetic glomerulus, and promoted both glomerular protection and endothelial barrier function. These important findings highlight a novel pathway for future investigation in the treatment of diabetic nephropathy

Contextual factors influencing implementation of tuberculosis digital adherence technologies: a scoping review guided by the RE-AIM framework.

INTRODUCTION: Digital adherence technologies (DATs) may enable person-centred tuberculosis (TB) treatment monitoring; however, implementation challenges may undermine their effectiveness. Using the reach, effectiveness, adoption, implementation and maintenance framework, we conducted a scoping review to identify contextual factors informing 'reach' (DAT engagement by people with TB) and 'adoption' (DAT uptake by healthcare providers or clinics). METHODS: We searched eight databases from 1 January 2000 to 25 April 2023 to identify all TB DAT studies. After extracting qualitative and quantitative findings, using thematic synthesis, we analysed common findings to create meta-themes informing DAT reach or adoption. Meta-themes were further organised using the Unified Theory of Acceptance and Use of Technology, which posits technology use is influenced by perceived usefulness, ease of use, social influences and facilitating conditions. RESULTS: 66 reports met inclusion criteria, with 61 reporting on DAT reach among people with TB and 27 reporting on DAT adoption by healthcare providers. Meta-themes promoting reach included perceptions that DATs improved medication adherence, facilitated communication with providers, made people feel more 'cared for' and enhanced convenience compared with alternative care models (perceived usefulness) and lowered stigma (social influences). Meta-themes limiting reach included literacy and language barriers and DAT technical complexity (ease of use); increased stigma (social influences) and suboptimal DAT function and complex cellular accessibility challenges (facilitating conditions). Meta-themes promoting adoption included perceptions that DATs improved care quality or efficiency (perceived usefulness). Meta-themes limiting adoption included negative DAT impacts on workload or employment and suboptimal accuracy of adherence data (perceived usefulness); and suboptimal DAT function, complex cellular accessibility challenges and insufficient provider training (facilitating conditions). Limitations of this review include the limited studies informing adoption meta-themes. CONCLUSION: This review identifies diverse contextual factors that can inform improvements in DAT design and implementation to achieve higher engagement by people with TB and healthcare providers, which could improve intervention effectiveness