179566 research outputs found
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Twenty-year trends in colectomy rates and advanced therapy prescribing in Lothian, Scotland
No full textBackground: The impact of advanced therapy prescribing on colectomy rates in ulcerative colitis (UC) is unknown with con-flicting published evidence.Aim: To describe advanced therapy prescribing trends and colectomy rates for patients with UC in Lothian, UK between January 1st, 2004 and December 31st, 2023.Methods: We obtained incidence and prevalence data from the Lothian IBD Registry, a rigorously validated population cohort. We report advanced therapy prescribing and colectomy data as raw numbers and annual incidence rates. We used piecewiselinear regression analyses to identify temporal trends in prescription and colectomy rates.Results: The prevalence of UC increased from 216 to 441 per 100,000 population in the 20 years from 2004, culminating in a total of 4115 patients with UC in 2023. We identified 720 patients who had received an advanced therapy. Prescribing of first-lineadvanced therapy increased from 0 in 2004 to 115 in 2023, equating to 0.00 and 2.82 per 100 patients with UC. We identified 563 patients of the prevalent UC population who had colectomy, of whom 68% were performed as emergencies. Absolute colectomy numbers decreased from 42 in 2004 to 7 in 2023, equating to 2.48 and 0.22 per 100 patients with UC. A join point in 2013 was found for both increased advanced therapy prescribing and decreased colectomy rates.Conclusion: The incidence of colectomy in the UC population has decreased over time while the use of advanced therapies has greatly increased
Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection: Analyses of national data for Brazil and Scotland
No full textObjectives: SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland.Design: We undertook a test-negative design study and nested case control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. . We used logistic regression to estimate odds ratios (OR) with 95% confidence intervals (95% CI). A stratified analysis assessed immunity during the Omicron dominant period in Brazil.Setting and participants: We included data from the adult populations of Brazil and Scotland, from 1 June 2020 to 30 April 2022.Outcome measures: Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase polymerase chain reaction or rapid antigen test confirmed at least 120 days after primary infection.Results: From Brazil, we included 30,881,873 tests and 1,301,665 severe COVID-19 outcomes, and from Scotland, we included 1,520,201 tests and 7,988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: <6 months post-primary infection: Brazil OR 0.10 (95%CI: 0.09 to 0.11), Scotland OR 0.01 (95%CI: 0.00 to 0.05); >12 months post-primary infection: Brazil OR 0.12 (95%CI: 0.10 to 0.14), Scotland OR 0.03 (95%CI: 0.02 to 0.04). For symptomatic reinfection,Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: <6 months post-primary infection: OR 0.19 (95%CI: 0.19 to 0.20); >12 months post-primary infection: OR 0.42 (95%CI: 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months post-primary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared to the overall study period, although protection against severe outcomes was sustained at 12 months post-primary infection (whole study: OR 0.12 (95%CI: 0.10 to 0.14); Omicron phase: OR 0.15 (95%CI: 0.12 to 0.19)).Conclusion: Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection
The political economy of investment protection reform in South American PTAs
No full textIn South America, investment chapters have been used by some governments, notably in Chile, Colombia and Peru, to replace outdated bilateral investment treaties and extend countries’ investment protection commitments. In other countries, such as Brazil, investment chapters are a means to rethink the governance of foreign investment altogether. This chapter traces the evolution of South America’s PTA investment chapters from 2001 to 2022, focusing on the types of reforms adopted and the domestic factors that shape the reforms governments are willing to accept. It finds that PTA investment chapters exhibit an increasing diversity of reforms over time, although the vast majority of agreements are designed to maintain traditional investment protection standards. This variation is partly driven by the legitimacy crisis of international investment law. Arguably, this crisis has created more political space for South American preferences in investment treaty lawmaking. However, who dominates reform debates is just as important for countries’ reform preferences as their experience with investor-state arbitration. Regardless of reform preferences, the main outcome of PTA investment chapters has been further fragmentation in an already complex and incomplete area of international economic law. This fragmentation, if allowed to continue, may exacerbate the very challenges that governments are seeking to address through their reform efforts in order to promote sustainable and inclusive development
Cancer-associated fibroblast driven paracrine 1 IL-6/STAT3 signaling promotes migration and dissemination in invasive lobular carcinoma
No full textBACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma of no special type (NST), accounting for 10-15% of diagnoses. Despite the myriad molecular, histological and clinical differences between ILC and NST tumors, patients are treated in the same way, and although prognosis initially is good, ILC patients have poorer long-term outcomes. Understanding the differences between these two subtypes and identifying ILC-enriched therapeutic targets is necessary to improve patient care.METHODS: Human and mouse cancer-associated fibroblasts (CAFs), ILC cell lines and patient-derived organoids were used for in vitro and in vivo studies, including western blotting, migration, organotypic invasion assays and dissemination in zebrafish embryos. RNASeq was used to identify CAF and interleukin-6 (IL-6)-derived gene signatures. Bioinformatic analysis of public databases and immunohistochemical of human tumor microarrays was carried out.RESULTS: We identified IL-6 as a paracrine CAF-derived factor that activates Signal-Transducer-and-Activator-of-Transcription-3 (STAT3) in human and mouse ILC models. Analysis of human breast tumors showed that the IL-6/JAK/STAT3 pathway is enriched in ER + ILC compared to ER + NST. A 42-gene CAF dependent IL-6 gene signature and 64-gene consensus IL-6 gene signature were generated and were significantly enriched in ER + ILC, with many of the genes overexpressed in ILC tumors. IL-6 treatment suppressed downstream estrogen signaling and also led to the acquisition of a more mesenchymal-like phenotype associated with increased migration and invasion. Finally, IL-6 treatment significantly increased ILC cell dissemination following injection into zebrafish embryos.CONCLUSIONS: CAF-derived IL-6 drives paracrine activation of the IL6/JAK/STAT3 signaling pathway which is enriched in ILC. This leads to the acquisition of pro-tumorigenic phenotypes, highlighting the pathway as a potential therapeutic target in ILC.</p
Exploring the disease experience and supportive care for people with very severe chronic obstructive pulmonary disease in Malaysia:a multiperspective qualitative study
No full textBACKGROUND: In Malaysia, palliative services are almost non-existent for those with severe organ failure such as chronic obstructive pulmonary disease (COPD). Access to palliative care services and awareness among the public and healthcare professionals remain low. While recognised as important in high income settings, the literature on palliative care for non-malignant disease is relatively uncommon in low- and middle-income countries, and none considered the multicultural setting of Malaysia. We aimed to explore the views and experiences of patients, healthcare providers (HCPs) and policymakers about their experience of very severe COPD and palliative care.METHODS: We undertook in-depth qualitative interviews with patients with very severe COPD, HCPs working in respiratory, palliative care, and primary care medicine, and health policymakers in Kuala Lumpur, Malaysia. Interviews followed a topic guide, were audio-recorded, transcribed verbatim, and analysed using a thematic analysis approach.RESULTS: We conducted 22 in-depth interviews with patients (n = 11), and physicians working in respiratory (n = 4), palliative care (n = 4) and primary care (n = 3) medicine. Four main themes emerged. First, there was poor understanding regarding severe, potentially life-limiting COPD and the need for palliative care. Second, patients were suffering from the severe physical, emotional, and psychosocial impact of the disease. Third, there was a lack of accessible, compassionate, holistic, and coordinated care. Finally, cultural issues such as religious norms, spirituality, community, and power hierarchies influenced patient care and acceptance of their condition.CONCLUSIONS: The Malaysian healthcare system is responding poorly to the needs of patients with very severe COPD. Raising awareness of these needs is the first step, but there needs to be a major change within the system if the care of this hidden neglected population is to be improved.</p
From hospital discharge to long-term care: Unmet rehabilitation needs in cauda equina syndrome patients from a national UK cohort
No full textSimple simulation based reconstruction of incidence rates from death data
No full textDaily deaths from an infectious disease provide a means for retrospectively inferring daily incidence, given knowledge of the infection-to-death interval distribution. Existing methods for doing so rely either on fitting simplified non-linear epidemic models to the deaths data or on spline based deconvolution approaches. The former runs the risk of introducing unintended artefacts via the model formulation, while the latter may be viewed as technically obscure, impeding uptake by practitioners. This note proposes a simple simulation based approach to inferring fatal incidence from deaths that requires minimal assumptions, is easy to understand, and allows testing of alternative hypothesized incidence trajectories. The aim is that in any future situation similar to the COVID pandemic, the method can be easily, rapidly, transparently, and uncontroversially deployed as an input to management
Liabilities on transfer of a business in Scots law:Who wants my genie in the bottle?
No full textCase note discussing Andrew Marr v Mackinnons LLP
Managing early-onset type 2 diabetes in the individual and at population level
No full textEarly-onset type 2 diabetes, diagnosed before age 40-years, is an increasingly prevalent condition with a more aggressive disease trajectory than late-onset type 2 diabetes. It is associated with accelerated microvascular and macrovascular complications, reduced life expectancy, and adverse pregnancy outcomes. Despite its rising incidence, globally, management strategies remain largely extrapolated from studies in older adults, with limited evidence specific to younger populations. This review aims to highlight the unique challenges in the management of early-onset type 2 diabetes and why current models of care are inadequate. We highlight that early-onset type 2 diabetes necessitates proactive and combination treatment strategies to address weight, the faster β-cell decline, worse insulin resistance and rapidly progressing hyperglycaemia. However, there is minimal evidence on how best to do this and clinical inertia risks contributing to glycaemic burden. Cardiovascular risk assessment tools underestimate long-term risk, contributing to low use of statin and antihypertensive therapy. Reproductive health remains a key concern, yet preconception and pregnancy care are inadequate, with low adherence to recommended interventions. Healthcare systems are not optimised to address the distinct needs of young adults, and gaps in transitional care (from paediatric to adult services) contribute to disengagement and adverse outcomes. Addressing these challenges requires tailored management strategies that consider the unique metabolic and psychosocial factors in this population. In this review, we summarise the evidence base for management of early-onset type 2 diabetes, the key evidence gaps and discuss the multi-sectoral and trans-disciplinary elements needed to achieve population-level prevention in an effort to reverse these concerning trends.<br/
Swarm Absolute Scalar Magnetometer Burst Mode: Observed ELF Signals and their Origins
No full textThe Absolute Scalar Magnetometers (ASM) onboard each European Space Agency Swarm satellites nominally provide 1 Hz magnetic scalar data. An additional experimental mode is available on the ASM consisting of a 250 Hz burst-mode which is periodically switched on allowing magnetic signals with frequencies up to 125 Hz to be investigated. By analysing burst-mode data from 2014 to 2023 in the frequency-time domain, we find a range of signals both man-made and geophysical, which we present here. Known features include lightning whistlers, auroral hiss and plasma bubbles that produce broadband incoherent signatures, and powerline harmonic radiation observed as stable 50 or 60 Hz lines. Ground based extremely low frequency (ELF) communication systems are also detected in the data. However, many as yet unexplained signals are observed. Rising tone 70–125 Hz high-intensity bursts, lasting ∼3 min, are found over the Antarctic, which we suggest are associated with local He+ ion gyrofrequencies and thus are possibly narrow-banded ionospheric hiss. These signals appear to be associated with the South Atlantic Anomaly due to their clustering on its southern edge, with the low field strength producing He+ gyrofrequencies less than 125 Hz. Additionally, extremely weak linear and quadratic chirps lasting tens of seconds to tens of minutes occur in the data without an obvious temporal or spatial trend which we tentatively attribute to onboard electronic or instrumental noise. Their origin requires further investigation to avoid artefacts in future magnetic missions. We also find long lasting, high frequency narrow-band features around 80–125 Hz which persist for 60–300 s, occurring orbit-on-orbit at fixed magnetic local times (MLT) around 0900 and 1500, mainly in equatorial latitudes, which are encountered during all burst sessions spanning these MLTs. The Swarm ASM burst-mode data suggest there are new geophysical magnetic phenomena yet to be fully understood, potentially offering new insights into magnetospheric and ionospheric wave-plasma interactions
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