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Introduction Alopecia areata (AA) is a common cause of immune-mediated non-scarring hair loss. Links between AA and common mental health, autoimmune and atopic conditions, and common infections have previously been described but remain incompletely elucidated and contemporary descriptions of the epidemiology of AA in the UK are lacking.\ud \ud \ud \ud Methods and analysis Retrospective study series using a large population-based cohort (5.2 million) from the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database, exploring four themes: AA epidemiology, mental health comorbidities, autoimmune/atopic associations and common infections.\ud \ud \ud \ud In the epidemiology theme, we will describe the incidence and point prevalence of AA overall and by age, sex and sociodemographic factors. Healthcare utilisation (primary care visits and secondary care referrals) and treatments for AA will also be assessed. In the mental health theme, we will explore the prevalence and incidence of mental health conditions (anxiety, depressive episodes, recurrent depressive disorder, adjustment disorder, agoraphobia, self-harm and parasuicide) in people with AA compared with matched controls. We will also explore the mental health treatment patterns (medication and psychological interventions), time off work and unemployment rates. Within the autoimmune/atopic associations theme, we will examine the prevalence of atopic (atopic dermatitis, allergic rhinitis, asthma) and autoimmune conditions (Crohn’s disease, ulcerative colitis, coeliac disease, type 1 diabetes, Hashimoto’s thyroiditis, Graves’ disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), polymyalgia rheumatica, Sjögren’s syndrome, psoriasis, vitiligo, multiple sclerosis, pernicious anaemia) in people with AA compared with matched controls. We will also estimate the incidence of new-onset atopic and autoimmune conditions after AA diagnosis. Within the common infections theme, we will examine the incidence of common infections (respiratory tract infection, pneumonia, acute bronchitis, influenza, skin infection, urinary tract infection, genital infections, gastrointestinal infection, herpes simplex, herpes zoster, meningitis, COVID-19) in people with AA compared with matched controls.\ud \ud \ud \ud Ethics and dissemination The Health Research Authority decision tool classed this a study of usual practice, ethics approval was not required. Study approval was granted by the RCGP RSC Study Approval Committee. Results will be disseminated through peer-reviewed publications.\ud \ud \ud \ud Observational study registration number NCT04239521.

The evolution of a Ni-YSZ microstructure under operation comprises the coarsening and the decrease of the contiguity of the Ni phase. The process occurs faster in the first thousand hours of operation and results in the progressive degradation of electrochemical performance because of the reduced density of connected triple-phase boundaries (TPB). A clear correlation between TPB density and performance of the solid oxide cell has been demonstrated over the past years. However, the effect of operation on the morphology of the Ni and YSZ surfaces near the TPBs is still unclear, despite the expected relevance for the electrode performance. Indeed, the gas species are first adsorbed on the surface of each solid phase and then diffuse to the TPBs before electrochemical reaction. Different Ni-YSZ cermet samples operated under solid oxide fuel cell (SOFC) and electrolysis (SOEC) conditions were imaged by 3-D focused ion beam - scanning electron microscopy (FIB-SEM) serial sectioning. Properties including phase size distribution, interfacial surface areas, and total and connected TPB density were first measured, before further characterization of the morphology close to the TPBs. A spilling algorithm was developed to characterize the surface available for diffusion on the YSZ and Ni surfaces for each TPB. Because the algorithm proceeds slice by slice, each diffusion surface is first treated as a line and referred to as an “available length”. The measurements along the three scanning directions of an analyzed volume are then merged for quantitative analyses. The evolution upon aging of the Ni available length distributions exhibited a slight diminution of the spread, resulting in a gathering toward a peak value (around 0.3 μm) and in a progressive decrease of the lengths larger than 0.5 μm. In the YSZ case, a shift toward larger lengths was observed, characterized by an increase of the modal value from 0.8 to 1 μm while maintaining a similar skewness. The behaviour during SOEC operation deviated for the two available measurements for the SOFC case. A percolation model that uses standard 3-D measurements as input was developed to investigate the evolution of the measured available lengths using simple geometrical concepts. The percolation model confirms the expected correlation between the growth of the particles and the decrease of total TPB lengths, likely related to a diminution of the number of particles per unit of volume. A sensitivity analysis was performed to capture the relationship between Ni coarsening and the increase of YSZ available lengths observed in the imaged samples. The study suggests a complex relationship between network and local morphology properties that are likely relevant for the effective electrocatalytic properties of the TPBs. The understanding of the correlations is expected to help improving both the electrode initial performance and the durability.

Despite the therapeutic value of calcitonin in treating bone disease, a biological role of endogenous calcitonin is controversial. Having previously demonstrated that the CTR has a biological role in protecting against calcium stress using a global CTRKO mouse model, the purpose of this study was to determine whether the protection conferred by the CTR during induced hypercalcemia is mediated via CTR expression on osteoclasts. Mice were generated, in which the CTR was deleted specifically within osteoclasts (OCL-CTRKOs) and compared with mice in which the CTR was deleted globally (global CTRKOs). Significantly, peak serum calcium levels following induced hypercalcemia were N18% higher in global-CTRKOs and OCL-CTRKOs than controls (Pb0.01) due to increased bone resorption (Pb0.05). Peak serum calcium levels relative to controls were greater in global-CTRKO males than OCL-CTRKO males (Pb0.001), which may, at least in part, be due to increased reabsorption of calcium in the kidney (Pb0.01). Controls for all analyses were sex-matched littermates with normal CTR expression. In conclusion, the CTR protects against hypercalcemia predominantly via its inhibitory action on osteoclasts. Refereed/Peer-reviewed

It is well established that calcitonin is a potent inhibitor of bone resorption; however, a physiological role for calcitonin acting through its cognate receptor, the calcitonin receptor (CTR), has not been identified. Data from previous genetically modified animal models have recognized a possible role for calcitonin and the CTR in controlling bone formation; however, interpretation of these data are complicated, in part because of their mixed genetic background. Therefore, to elucidate the physiological role of the CTR in calcium and bone metabolism, we generated a viable global CTR knockout (KO) mouse model using the Cre/loxP system, in which the CTR is globally deleted by >94% but