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Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47–59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5–3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3–3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support. [ABSTRACT FROM AUTHOR]

Abstract Stratospheric aerosol injection (SAI) has been shown in climate models to reduce some impacts of global warming in the Arctic, including the loss of sea ice, permafrost thaw, and reduction of Greenland Ice Sheet (GrIS) mass; SAI at high latitudes could preferentially target these impacts. In this study, we use the Community Earth System Model to simulate two Arctic‐focused SAI strategies, which inject at 60°N latitude each spring with injection rates adjusted to either maintain September Arctic sea ice at 2030 levels (“Arctic Low”) or restore it to 2010 levels (“Arctic High”). Both simulations maintain or restore September sea ice to within 10% of their respective targets, reduce permafrost thaw, and increase GrIS surface mass balance by reducing runoff. Arctic High reduces these impacts more effectively than a globally focused SAI strategy that injects similar quantities of SO2 at lower latitudes. However, Arctic‐focused SAI is not merely a “reset button” for the Arctic climate, but brings about a novel climate state, including changes to the seasonal cycles of Northern Hemisphere temperature and sea ice and less high‐latitude carbon uptake relative to SSP2‐4.5. Additionally, while Arctic‐focused SAI produces the most cooling near the pole, its effects are not confined to the Arctic, including detectable cooling throughout most of the northern hemisphere for both simulations, increased mid‐latitude sulfur deposition, and a southward shift of the location of the Intertropical Convergence Zone. For these reasons, it would be incorrect to consider Arctic‐focused SAI as “local” geoengineering, even when compared to a globally focused strategy.

Oestrogen receptor (ER) is arguably the single most important biological predictive factor that exists today. In the last 10 years or so, however, our understanding of ER biology has undergone a paradigm shift following the identification of a second ER, ERβ, with the original ER being renamed ERα. A number of isoforms have additionally been described, especially for ERβ. Our knowledge of ER signalling has also increased with the recognition of accessory co-regulatory proteins, which help direct the transcriptional cascade. Here we outline these changes and discuss what biological and clinical implications these could have in the mammary gland. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

There is a clear association between the development of breast cancer and increasing age, with 80% of cancers occurring in women more than 50 years of age and one-third in women over 70 years. Following the menopause the breast undergoes involution, with the main changes affecting the terminal ductal lobular unit. There is an increase in oestrogen receptor alpha (ERα)-positive cells, a decrease in proliferation but, in comparison to premenopausal breasts, a greater number of ERα-proliferating cells. The breast cancers that occur in women ≥ 75 years are more likely to be ER-positive, with a low growth rate and limited expression of HER-2 and p53. It is proposed that uneven involution of the breast, the persistence of at-risk lesions, the presence of ERα-proliferating cells and local oestrogen metabolism in breast adipose tissue are factors in the development of breast cancers with a well-differentiated phenotype. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Several childhood neurological conditions can lead to problems with unintended access to the mouth. Earlier workers have demonstrated benefits in the use of a helmet restricting mouth access, within a behavioural modification programme. Conventionally, such headgear is very obtrusive. This paper presents a simple technique using conventional plaster-based moulding, which has been successfully used in making secure, minimally obtrusive masks. Masks produced for two children have been readily accepted and have been successful. Any such headgear should be used only within a managed behavioural modification programme. [ABSTRACT FROM PUBLISHER]