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Bringing social and cultural dimensions into environmental flows (eflows) is critical for sustainable river management, yet structured methods for this process are lacking. We tested the efficacy of a Driver-Pressure-State-Impact-Response (DPSIR) framework, quantified with Fuzzy Cognitive Mapping (FCM), to bridge ecological processes and social-cultural-spiritual values for the regulated Wolastoq | Saint John River | fleuve Saint-Jean, a large transboundary watershed in Maritime Canada. We integrated data from expert-led workshops, which produced 69 refined flow-ecology hypotheses, and a public survey on social-cultural-spiritual connections to the river. The resulting semi-quantitative model revealed a complex network of 39 social-ecological nodes with 941 positive and negative connections and provided a visual map of these connections. Network analysis identified flow variability (an environmental stressor) and peace + tranquility (a social-cultural-spiritual state) as the most significant nodes within the map, acting as critical bridges between the environmental and human domains. The framework explicitly linked physical processes and flow management actions, like hydropeaking, to tangible impacts on ecosystem health (e.g., water quality and biodiversity), recreational access, and community well-being, while also highlighting a potential feedback loop where a sense of peace also promotes environmental stewardship. Our findings demonstrate that the DPSIR-FCM approach is a powerful tool for creating a holistic, transparent, and socially defensible foundation for eflows management. It translates complex social-ecological interactions into an actionable decision-support tool that prioritizes management decisions that promote inclusive, evidence-based water governance.

Background: Troponin levels are elevated in some acute stroke patients, but the clinical significance of this is unclear. Methods: We conducted a systematic review of studies measuring troponin within 7 days of symptom onset in acute stroke patients. Results: We identified 15 studies (2,901 patients). Overall 18.1% (95% CI 13.6–22.6) had a positive troponin level. These patients were more likely to have electrocardiogram (ECG) changes suggestive of myocardial ischemia (OR 3.0; 95% CI 1.5–6.2), and there was an independent association with death (OR 2.9; 95% CI 1.7–4.8). Conclusion: Elevated troponin level after acute stroke is common and is associated with ECG changes suggestive of myocardial ischemia and increased risk of death.

Background: Reduced socioeconomic status (SES) is associated with an increased risk of stroke, although the mechanism is not clear. It may be that those with lower SES have a greater burden of classic vascular risk factors. Methods: Our aim was to quantify the extent to which classic vascular risk factors explain the association between SES and stroke incidence. We conducted a systematic review and meta-analysis of studies examining the association of SES and stroke incidence, where classic vascular risk factors were considered. Searching MEDLINE, EMBASE and the Cochrane Library from 1980 onwards we identified 17 studies, 12 of these studies provided sufficient information to allow a meta-analysis. From each study the increased risk of stroke incidence, where the lowest socioeconomic category was compared with the highest, was recorded and pooled. The stroke incidence risks, adjusted for grouped classic risk factors, were also pooled. Review Manager 5 software was used for all analyses and results were analysed using hazard ratios (HR, 95% confidence interval, 95% CI) with a random effects model. Results: Those with a lower SES were more likely to have a stroke (HR 1.67; 95% CI 1.46–1.91). Additional risk was reduced, but not eliminated, when classic vascular risk factors were adjusted for (HR 1.31; 95% CI 1.16–1.48). Conclusion: Low SES is associated with an increased risk of stroke that is partly explained by known classic vascular risk factors.

Glycogen synthase kinase 3β (GSK3β) is phosphorylated and inactivated by the phosphoinositide 3 kinase PI3K/Akt pathway. Activation of Akt phosphorylates GSK3β preventing phosphorylation of cyclin D1 which leads to accumulation and nuclear localisation of cyclin D1, activation of CDK4/6 and cell cycle progression. The CCND1 gene found at chromosome 11q13 has been shown to be amplified in approximately 15 % of breast cancers. Cyclin D1, the product of the CCND1 gene, is one of the most commonly overexpressed proteins in breast cancer. Protein expression for GSK3β, phosphorylated-GSK3β (p-GSK3β), cyclin D1 and gene expression of CCND1 were examined in tissue microarrays of 1,686 patients from the Edinburgh Breast Conservation Series. High GSK3β expression was associated with reduced distant relapse-free survival (DRFS), while no association between p-GSK3β and breast cancer-specific survival was seen. CCND1 amplification is also associated with poor DRFS. On the contrary, cyclin D1 overexpression is associated with an increase in DRFS. Multivariate analysis was performed. We suggest that analysis of both GSK3β and cyclin D1 expressions can be considered as a marker of good prognosis in early breast cancer.

Purpose The aim of this study was to investigate the potential benefits of prolonged treatment with neoadjuvant letrozole. Patients and Methods About 182 consecutive patients have been treated in Edinburgh with neoadjuvant letrozole for 3 months or longer and 63 patients have continued on letrozole beyond 3 months. Outcomes are reported. Results Of the 63 patients who continued on letrozole, 38 patients took letrozole for more than 1 year and 23 took letrozole for more than 24 months. The median reduction in clinical volume in the first 3 months in these 63 patients was 52%. Similar reductions in median clinical volume were seen between three to 6 months (50%), 6-12 months and 12-24 months (medians 37 and 33%, respectively). At 3 months 69.8% of the 182 patients had a partial or complete response. The response rate increased to 83.5% with prolonged letrozole treatment. Continuing letrozole beyond 3 months increased the number of women who initially required mastectomy or had locally advanced breast cancer who were subsequently suitable for breast conserving surgery from 60% (81/134) at 3 months to 72% (96/134). Thirty-three women remain on letrozole alone (man age at diagnosis 83 years) and at 3 years the median time to treatment failure has not been reached. Conclusion Continuing letrozole in responding patients beyond 3-4 months achieves further clinical reduction in tumour size. For elderly women with a short life expectancy letrozole alone may provide long-term disease control.

Background: Lower socioeconomic status (SES) is associated with an increased risk of stroke but the mechanisms are unclear. We aimed to determine whether low-SES stroke/transient ischaemic attack (TIA) patients have a greater burden of vascular risk factors/co-morbidity and reduced health care access. Methods: We prospectively studied 467 consecutive stroke and TIA patients from 3 Scottish hospitals (outpatients and inpatients) during 2007/2008. We recorded vascular risk factors, stroke severity, co-morbidity measures, investigations and health service utilisation. SES was derived from postcodes using Scottish Neighbourhood Statistics and analysed in quartiles. Results: TIA/stroke patients in the lowest SES quartile were younger (64 years, SD 14.1) than those in the highest quartile (72 years, SD 12.9; p < 0.0001). They were more likely to be current smokers (42 vs. 22%; p = 0.001) but there was no association with other vascular risk factors/co-morbidity. There was a trend for those with lower SES to have a more severe stroke [modified National Institutes of Health Stroke Scale score and interquartile range: 4 (2–6) vs. 3 (1–5); multivariate p = 0.05]. Lower SES groups were less likely to have neuro-imaging (82 vs. 90%; p = 0.036) or an electrocardiogram (72 vs. 87%; p = 0.003), but differences were no longer significant on multivariate analysis. However, there was equal access to stroke unit care. Conclusions: Low-SES TIA and stroke patients are younger and have a more severe deficit; an increased prevalence of smoking is likely to be a major contributor. We found equal access to stroke unit care for low-SES patients.

The Nottingham Prognostic Index Plus (NPI+) is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent series of BC. Eight hundred and eighty five primary early stage BC cases from Edinburgh were semi‐quantitatively assessed for 10 biomarkers [Estrogen Receptor (ER), Progesterone Receptor (PgR), cytokeratin (CK) 5/6, CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin 1] using immunohistochemistry and classified into biological classes by fuzzy logic‐derived algorithms previously developed in the Nottingham series. Subsequently, NPI+ Prognostic Groups (PGs) were assigned for each class using bespoke NPI‐like formulae, previously developed in each NPI+ biological class of the Nottingham series, utilising clinicopathological parameters: number of positive nodes, pathological tumour size, stage, tubule formation, nuclear pleomorphism and mitotic counts. Biological classes and PGs were compared between the Edinburgh and Nottingham series using Cramer's V and their role in patient outcome prediction using Kaplan–Meier curves and tested using Log Rank. The NPI+ biomarker panel classified the Edinburgh series into seven biological classes similar to the Nottingham series (p > 0.01). The biological classes were significantly associated with patient outcome (p < 0.001). PGs were comparable in predicting patient outcome between series in Luminal A, Basal p53 altered, HER2+/ER+ tumours (p > 0.01). The good PGs were similarly validated in Luminal B, Basal p53 normal, HER2+/ER− tumours and the poor PG in the Luminal N class (p > 0.01). Due to small patient numbers assigned to the remaining PGs, Luminal N, Luminal B, Basal p53 normal and HER2+/ER− classes could not be validated. This study demonstrates the reproducibility of NPI+ and confirmed its prognostic value in an independent cohort of primary BC. Further validation in large randomised controlled trial material is warranted.

Cochlear implantation is an expensive but effective lifelong intervention for individuals with a severe-to-profound hearing loss. The primary aim of this study was to survey the short- and long-term costs of cochlear implantation. Individuals (N=154) using cochlear implants obtained from the University of Stellenbosch-Tygerberg Hospital Cochlear Implant Unit in Cape Town, South Africa were surveyed using a questionnaire and patient record review. The questionnaire used a combination of closed and open-ended questions to gather both quantitative and qualitative information. Costs were categorised as short- and long-term costs. All costs were converted to constant rands (June 2010) using the Consumer Price Index to allow for comparison in real terms over time. In the first 10 years of implantation the average estimated costs incurred by adults totalled R379 626, and by children R455 225. The initial purchase of the implant system was the most substantial cost, followed by upgrading of the processor. Travel and accommodation costs peaked in the first 2 years. On average the participants spent R2 550 per year on batteries and spares. Rehabilitation for children cost an average of R7 200. Insurance costs averaged R4 040 per year, and processor repairs R3 000 each. In addition to the upfront expense of obtaining the cochlear implant system, individuals using a cochlear implant in South Africa should be prepared for the long-term costs of maintenance, accessing the unit, support services and additional costs associated with use. Knowledge of these costs is important to ensure that individuals are successful users of their cochlear implants in the long term.

Mehanna and colleagues highlight the increasing incidence of oral and oropharyngeal cancer in the United Kingdom and its likely association with sexually transmitted human papilloma virus (HPV).