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Towards understanding stellar variability at the sub m/s level: isolating granulation signals in synthetic spectral lines
No full textGranulation in the photospheres of FGK-type stars induces variability in absorption lines, complicating exoplanet detection via radial velocities and characterization via transmission spectroscopy. We aim to quantify the impact of granulation on the radial velocity and bisector asymmetry of stellar absorption lines of varying strengths and at different limb angles. We use 3D radiation-hydrodynamic simulations from MURaM paired with MPS-ATLAS radiative transfer calculations to synthesize time series for four Fe i lines at different limb angles for a solar-type star. Our line profiles are synthesized at an extremely high resolution (R = 2000 000), exceeding what is possible observationally and allowing us to capture intricate line shape variations. We introduce a new method of classifying the stellar surface into three components and use this to parametrize the line profiles. Our parametrization method allows us to disentangle the contributions from p-modes and granulation, providing the unique opportunity to study the effects of granulation without contamination from p-mode effects. We validate our method by comparing radial velocity power spectra of our granulation time series to observations from the Laser-based Absolute Reference Spectrograph. We find that we are able to replicate the granulation component extracted from observations of the Fe i 617 nm line at the solar disc centre. We use our granulation-isolated results to show variations in convective blueshift and bisector asymmetry at different limb angles, finding good agreement with empirical results. We show that weaker lines have higher velocity contrast between granules and lanes, resulting in higher granulation-induced velocity fluctuations. Our parametrization provides a computationally efficient strategy to construct new line profiles, laying the groundwork for future improvements in mitigating stellar noise in exoplanet studies
Consuming grass finished lamb improves blood plasma ω-3 fatty acid response among healthy consumers
No full textBackground and purposeDietary intakes of omega-3 polyunsaturated fatty acids (ω-3 PUFA) are below what is recommended. Meat from grass finished ruminants contains higher levels of ω-3 PUFAs, particularly, alpha-linolenic acid (C18:3 ω-3). The impact of consuming grass finished lamb meat rich in ω-3 PUFA on blood fatty acid (FA) response in humans is not well established. This study investigated the impact of consuming grass finished lamb on total blood plasma and blood plasma phospholipids (PL) FA and on cardiovascular risk factors, including heart rate, blood pressure (BP), HDL, LDL, total cholesterol, and TAG, in humans.MethodsA single blinded, randomised controlled trial was conducted. Two portions of lamb chops and one portion of lamb mince from lambs finished on a grass or concentrate diet were consumed per week by 34 healthy participants for four consecutive weeks. Blood samples were taken at baseline and post-intervention. Approximately ~ 328 mg/100 g of total ω-3 PUFA was present in grass finished lamb portions per week.ResultsGreater levels of ω-3 PUFA, namely C18:3 ω-3, eicosapentaenoic acid (C20:5 ω-3) and docosapentaenoic acid (C22:5 ω-3), were detected in total blood plasma from participants who consumed grass finished lamb (P < 0.05), while consuming concentrate finished lamb higher levels of linoleic acid (C18:2 ω-6) in plasma PL (P < 0.01). There were no differences of consuming grass or concentrate finished lamb on cardiovascular risk factors.ConclusionThis study demonstrates that ω-3 PUFA from lamb meat finished on grass is reflected in blood ω-3 PUFA response. Grass finished lamb is a useful matrix for increasing intake of ω-3 PUFA into the human body alongside little required change to customary dietary habits.<br/
Chemotherapy and radiotherapy use in patients with lung cancer in Australia, Canada, the UK and Norway 2012-2017: an ICBP population-based study
No full textBACKGROUND: International variation in lung cancer survival may be partly explained by variation in stage-specific treatment use, but relevant comparative evidence is sparse. As part of the International Cancer Benchmarking Partnership, we examined use of chemotherapy and radiotherapy in population-based cancer registry data.METHODS: Linked population-based data sources were used to describe use and time to first treatment for either chemotherapy or radiotherapy in patients with lung cancer diagnosed in study periods during 2012-2017 in 16 jurisdictions of Australia, Canada, the UK and Norway.RESULTS: There was large variation in the proportions of patients with lung cancer receiving chemotherapy (ranging from 23% in Northern Ireland to 45% in Norway) and radiotherapy (ranging from 32% in England to 48% in New South Wales and 50% in Newfoundland and Labrador). Across jurisdictions, chemotherapy use decreased steeply with increasing age, regardless of stage at diagnosis. For radiotherapy use, in stage 1-3 cancer three patterns were observed: (a) steep decrease with increasing age (UK jurisdictions, Saskatchewan-Manitoba); (b) a relatively flat pattern (Norway, Alberta, British Columbia, Atlantic Canada, New South Wales) and (c) increasing use with increasing age (Ontario).Time to radiotherapy initiation was longer in the UK jurisdictions than elsewhere; time to chemotherapy was longer in the UK and Canadian jurisdictions except Ontario.DISCUSSION: Use of chemotherapy and radiotherapy in patients with lung cancer varied substantially between jurisdictions during the mid-2010s within age-stage strata. Reasons for these variations are unclear. Differences in non-surgical treatment use are plausibly associated with international variation in lung cancer survival.</p
Time to use hospital passports: their use to improve the health outcomes of people with intellectual disabilities
No full textEfficacy of mineralocorticoid receptor antagonists on kidney and cardiovascular outcomes in patients with chronic kidney disease: an umbrella review
No full textRationale & Objective: To comprehensively summarize the efficacy of mineralocorticoid receptor antagonists (MRAs) to improve kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD). Study Design: Relevant studies were identified from Medline and Scopus databases from their inception up to August 2023.Setting & Study Populations: Patients with nondialysis or dialysis CKD. Selection Criteria for Studies: Systematic reviews and meta-analyses (SR-MAs) of randomized controlled trials (RCTs) that investigated the efficacy of MRAs on kidney and CV outcomes in patients with nondialysis or dialysis CKD were included in this study. Data Extraction: Characteristics of studies and participants, and treatment effects were extracted. Analytic Approach: Efficacy of MRAs was qualitatively summarized according to types of patients and MRAs. Results: Forty SR-MAs were included. When compared with placebo/usual care, steroidal MRAs (sMRAs) provided significant benefit in decreasing all-cause (pooled RRs of 0.38 [0.22-0.65] to 0.87 [0.77-0.98]) and CV mortality (pooled RRs of 0.34 [0.15-0.75] to 0.46 [0.28-0.76]) only in patients treated with dialysis, when compared with placebo. Nonsteroidal MRAs (nsMRAs) significantly lowered composite CV events in both nondialysis CKD (pooled RRs of 0.86 [0.79-0.94] to 0.92 [0.85-0.99]) and patients with diabetic kidney disease (DKD) (pooled RRs of 0.86 [0.78-0.95] to 0.88 [0.81-0.96]). In addition, nsMRAs showed significant benefit in reducing composite kidney outcomes in patients with either nondialysis CKD or DKD when compared with placebo. However, this efficacy was lower than sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with DKD. Moreover, both sMRAs and nsMRAs significantly increased the risk of hyperkalemia in patients with nondialysis CKD and DKD. Limitations: The comparison between nsMRAs and SGLT2i is based on network meta-analyses. Consequently, additional head-to-head RCTs are necessary to confirm the advantages of SGLT2i over nsMRAs. Conclusions: sMRAs offer benefits in reducing all-cause and cardiovascular mortality and composite CV events in patients treated with dialysis. nsMRAs improve kidney outcomes in patients with nondialysis CKD and DKD but increase hyperkalemia risk. Plain Language Summary: Chronic kidney disease (CKD) can increase the risk of severe kidney problems and heart disease. A key factor in kidney decline and heart disease risk is the overactivation of mineralocorticoid receptors (MR). Medications called MR antagonists (MRAs) may lower heart disease risk. We performed a thorough review of all existing studies on both steroidal MRAs (sMRAs) and nonsteroidal MR antagonists (nsMRAs) to see how they might help reduce kidney and heart problems in different types of CKD. Our review found that sMRAs significantly lower the risk of death from all causes and heart issues in patients treated with dialysis, whereas nsMRAs reduce the chances of heart and kidney problems in patients not requiring dialysis. Both types of MRAs, however, do increase the risk of high potassium in patients requiring nondialysis.</p
Stress adaptation under in vitro evolution influences survival and metabolic phenotypes of clinical and environmental strains of Vibrio cholerae El-Tor
No full textBacterial adaptation to stress can lead to phenotypic variants with diverse levels of niche competitiveness, pathogenicity, and antimicrobial resistance. In this work, we employed experimental evolution to investigate whether exposure to various stress conditions results in new phenotypic and metabolic properties in clinical and environmental strains of Vibrio cholerae. Our findings revealed the emergence of variants with metabolic and genetic variations and enhanced survival under stress compared to the parental isolates. Phenotypic changes in the evolved variants included colony morphology, biofilm formation, and the appearance of proteolytic and hemolytic activities. The variants demonstrated metabolic changes in the preferred use of carbon, nitrogen, phosphorous, and sulfur substrates, while the genetic changes included single nucleotide polymorphisms (SNPs), breakpoints, translocations, and single nucleotide insertions and deletions. Mutations in genes encoding EAL and HD-GYP domain-containing proteins correlated with increased biofilm formation and different colony morphotypes. The combined analysis of the metabolic and genomic data pointed to pathways implicated in stress survival. The environmental strains were generally more pathogenic than the clinical strains in the Galleria mellonella infection model prior to the experimental evolution, and these differences did not change in the evolved variants. This study highlights the contribution of stress conditions as drivers for the evolution of genetic modifications and metabolic adaptation in V. cholerae, which may explain the continuous evolution of El-Tor biotype strains toward variants with improved survival in the environment.<br/
Paton Prize lecture winner 2024: Gordon Holmes and the Irish spirit of adventure: lessons for modern thinkers
No full textThis lecture is given in honour of Sir William Paton (1917–1993), physiologist, pharmacologist and Fellow of the Royal Society. His passion for the history of medicine led to generous donations to the Society, who consequently founded the Paton Prize Fund for historical research. After his death, this eponymous Prize Lecture was debuted in 1994. It has been a singular honour for me to acclaim the similarly influential Irish neurologist Gordon Morgan Holmes (1876–1965), whose work has been a particular preoccupation of mine for my entire career, since I first heard of him as an undergraduate in 1991. Holmes’ work on the World War I battlefield completely transformed neurology, in terms both of clinical practice and its knowledge base. Clinical techniques developed by him at that time remain established current practice, and his visual field maps were not superseded for 73 years. His legacy to neurology is extensive, with his editorship of the journal Brain from 1922 to 1937. He had a profound influence both here and across the Atlantic, evinced by global warm tributes published on his death in 1965. The Lecture concentrates on a confluence of events and circumstances existing in the Flanders trenches that met a man singularly suited to overcoming the challenges posed. He received training in neuroanatomy from the German anatomists and clinical skills from the British greats in the National Hospital Queen Square. Coupled with an Irish adventurousness and insatiable curiosity, this experience presaged advances that resonate >100 years on. His legacy speaks profoundly of curiosity, interdisciplinarity and reconciliation.<br/
A novel method for subgroup discovery in precision medicine based on topological data analysis
No full textBackgroundThe Mapper algorithm is a data mining topological tool that can help us to obtain higher level understanding of disease by visualising the structure of patient data as a similarity graph. It has been successfully applied for exploratory analysis of cancer data in the past, delivering several significant subgroup discoveries. Using the Mapper algorithm in practice requires setting up multiple parameters. The graph then needs to be manually analysed according to a research question at hand. It has been highlighted in the literature that Mapper’s parameters have significant impact on the output graph shape and there is no established way to select their optimal values. Hence while using the Mapper algorithm, different parameter values and consequently different output graphs need to be studied. This prevents routine application of the Mapper algorithm in real world settings.MethodsWe propose a new algorithm for subgroup discovery within the Mapper graph. We refer to the task as hotspot detection as it is designed to identify homogenous and geometrically compact subsets of patients, which are distinct with respect to their clinical or molecular profiles (e.g. survival). Furthermore, we propose to include the existence of a hotspot as a criterion while searching the parameter space, addressing one of the key limitations of the Mapper algorithm (i.e. parameter selection).ResultsTwo experiments were performed to demonstrate the efficacy of the algorithm, including an artificial hotspot in the Two Circles dataset and a real world case study of subgroup discovery in oestrogen receptor-positive breast cancer. Our hotspot detection algorithm successfully identified graphs containing homogenous communities of nodes within the Two Circles dataset. When applied to gene expression data of ER+ breast cancer patients, appropriate parameters were identified to generate a Mapper graph revealing a hotspot of ER+ patients with poor prognosis and characteristic patterns of gene expression. This was subsequently confirmed in an independent breast cancer dataset.ConclusionsOur proposed method can be effectively applied for subgroup discovery with pathology data. It allows us to find optimal parameters of the Mapper algorithm, bridging the gap between its potential and the translational research.<br/