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New scientific evidence for the history and occupants of Tomb I (“Tomb of Persephone”) in the Great Tumulus at Vergina
Get PDFThe Great Tumulus of Vergina (Aegae) is considered to be the royal burial complex of the Macedonian kings. Beneath it four tombs were discovered, labeled Tomb I, II, III and IV. Several hypotheses have been proposed for the identities of the occupants of the “royal tombs”, but without scientific backing. We present new data from Tomb I (“The Tomb of Persephone”), which contained inhumed (unburnt), in situ and commingled adult skeletal remains, as well as commingled nonadult and animal bones. We applied a range of scientific techniques, including radiocarbon dating, ancient DNA (aDNA), strontium and stable carbon and nitrogen isotope analysis, supported by osteological and odontological observations on the adult and nonadult bones found in Tomb I to provide concrete evidence for the date of burials, sex, age at death and origin of the individuals interred in this tomb. Our results show that, with the exception of four bones that were identified as female, all the adult bones are male according to the aDNA and osteological results, and they belonged to a man aged 25–35 years with a stature of approximately 167 cm. Radiocarbon dating places this burial in the first half of the 4th century calBC, specifically between 400 and 367 calBC, and by applying a potential collagen offset correction this is slightly shifted to 388-356 calBC at the latest. The female bones date to the same period. However, all the nonadults and animal bones, date to the Roman period from 150 calBC, the earliest to 130 calAD the latest. Therefore, these are not related to the primary adult burials. The male occupant was most likely an important Macedonian royal of the Argead/Temenid house who died in the period 388-356 calBC and was probably honored or worshipped in the shrine above and entombed likely together with a female. Previous suggestions that the skeletal remains belong to Philip II, his wife Cleopatra and newborn child are not scientifically sustainable
Design and rationale of the drug-coated balloon coronary angioplasty versus stenting for treatment of disease adjacent to a chronic total occlusion (Co-CTO) trial
Get PDFBackground
Percutaneous coronary intervention (PCI) of chronic total coronary occlusions (CTOs) typically involves extensive drug-eluting stent (DES) implantation. As a result, patients undergoing CTO PCI are exposed to a relatively high risk of in-stent restenosis and target lesion revascularization. While the application of drug-coated balloons (DCBs) may improve patient outcome by reducing stent burden, randomized controlled trials investigating the use of DCB in CTO PCI are lacking.
Methods
The Co-CTO trial (NCT04881812) is a single-blind, noninferiority randomized controlled trial enrolling 144 patients undergoing CTO PCI. A hybrid strategy (stenting of the CTO body and DCB treatment of adjacent disease) will be compared to a complete stenting strategy. The primary study endpoint is in-segment percentage diameter stenosis at 1 year follow-up determined by intravascular ultrasound. Secondary endpoints include major adverse cardiovascular events (a composite of cardiac death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization) at 1 year, angiographic outcomes, and cardiac symptoms (Canadian Cardiovascular Society Grading Scale, New York Heart Association Classification of Dyspnea).
Conclusion
The Co-CTO trial is the first randomized controlled trial exploring a hybrid strategy (DES + DCB) in patients undergoing CTO PCI.
Trial registration
Registered at ClinicalTrials.Gov under registration number: NCT04881812 (https://clinicaltrials.gov/study/NCT04881812?cond=cto&intr=drug-coated%20balloon&rank=1)
Remote pulmonary artery pressure-guided management of patients with heart failure: A clinical consensus statement of the Heart Failure Association (HFA) of the ESC
Get PDFEpisodes of worsening heart failure (HF) are a major cause of unplanned hospitalizations. Their onset is usually preceded by an early increase in intracardiac pressures with subsequent worsening of symptoms due to congestion. Implantable devices allowing daily remote pulmonary artery pressure (PAP) monitoring are useful to identify early haemodynamic changes so that medical therapy can be adjusted at an early stage, before symptom onset, and HF‐related hospitalizations be prevented. Second, the use of these devices may help to maintain clinical stability keeping PAP in the target range on a day‐to‐day basis. The CardioMEMS system allows remote PAP monitoring, and PAP‐guided medical therapy has reduced HF‐related hospitalizations in prospective, randomized, controlled clinical trials in symptomatic patients with HF, independent of their left ventricular ejection fraction. The safety and feasibility of other devices, like the Cordella implantable PAP sensor, have also been demonstrated and clinical usefulness in larger patient populations is currently being assessed in several trials. Most of the studies testing remote PAP monitoring were reported after the 2021 European Society of Cardiology HF guidelines. An update of the clinical significance and potential implications for clinical practice of these systems seems therefore warranted. The aim of this clinical consensus statement is to summarize current knowledge on remote PAP‐guided management of patients with HF, with a special focus on current evidence from clinical trials, potential impact on clinical practice and management aspects
Priority setting for nutrition research in individuals with spinal cord injury: A protocol for Delphi study among health professionals
Get PDFStudy design
A protocol for Delphi Consensus Study.
Objectives
To identify a top ten list of priorities for future nutrition research in individuals with spinal cord injury (SCI).
Setting
The International Spinal Cord Society (ISCoS) Nutrition Specialist Interest Group (SIG) priority setting partnership was established in 2024 to conduct this international Delphi study through online surveys and a hybrid meeting.
Methods
The study involves THREE key stages: topic generation, priority ranking, and consensus building. In phase 1, participants will generate potential research topics via an online survey. Phase 2 involves ranking the top 10 research priorities on a 9-point Likert scale. Phase 3 consists of a consensus meeting where stakeholders will engage in discussions and vote on the final priorities using interactive tools. For Phases 1 and 2, both ISCoS Nutrition SIG members and their professional contacts will be invited to participate, ensuring a diverse pool of expertise. Phase 3 will be limited to Nutrition SIG members to facilitate focused decision-making. Data will be collected through secure Qualtrics surveys and analysed using descriptive statistics in STATA or SPSS. The study adheres to the Conducting and Reporting of DElphi Studies (CREDES) recommendations and employs rigorous data management practices compliant with City St George’s, University of London standards.
Ethics and dissemination
Ethics approval has been granted (ref: ETH2425−0192, Health Services Research & Management Proportionate Review Committee, City St George’s, University of London). The findings will be disseminated through ISCoS website, professional conferences and a peer-reviewed journal
Moving beyond the noise: geospatial modelling of urban sound environments in a sub-Saharan African city
Get PDFCities encompass a mixture of artificial, human, animal, and nature-based sounds, which through long and short-term exposures, can impact on physical and mental health. Yet, most epidemiological research has focused on only transportation noise, leaving a significant gap in understanding the health impacts of other urban sound types, especially in sub-Saharan Africa (SSA). We conducted a large-scale measurement campaign in Accra, Ghana, collecting audio recordings and sound levels from 129 locations between April 2019-June 2020. We classified sound types with a neural network model and then used Random Forest land use regression to predict prevalences of different sound types citywide. We then developed a composite metric integrating sound levels with the prevalence of sound types. Road traffic sounds dominated the urban core, while human and animal sounds were prominent in high-density and peri-urban areas, respectively. Our high-resolution approach provides a comprehensive characterization of the complexity of urban sounds in a major SSA city, paving the way for new epidemiological studies on the health impacts of exposure to diverse sound sources in the future
Recent Advances in the Diagnosis of Talaromycosis
Get PDFTalaromycosis is an invasive fungal disease endemic to Southeast Asia. While culture is essential in identification, susceptibility testing, and typing, the low sensitivity and long turnaround times limit its clinical utility. Several promising monoclonal antibody–based (MAb) antigen-detection assays have been evaluated in large patient cohorts. This includes the MAb-Mp1p and MAb-4D1 enzyme immunoassays and their point-of-care platforms. Quantitative polymerase chain reaction (qPCR) assays targeting the 5.8S or 18S region of ribosomal RNA have been developed. These antigen and qPCR assays are highly specific and more sensitive than blood culture, making them excellent rapid rule-in tests for talaromycosis in people with a compatible clinical syndrome. Metagenomic next-generation sequencing is emerging as a promising tool for non-bias detection of talaromycosis. Host-based diagnostics targeting antibodies, interferon-gamma release, and transcriptomics are being actively developed. This review summarizes recent advances in the diagnosis of talaromycosis and provides expert recommendations on the application of these novel tests to improve the diagnostic algorithm and management of talaromycosis
Retinal Vessel Traits and Age‐Related Eye Disease in the Canadian Longitudinal Study on Aging
Get PDFBackground
To cross‐sectionally and longitudinally examine whether retinal vessel traits are associated with glaucoma‐related outcomes (glaucoma, cup‐to‐disc ratio [CDR] and intraocular pressure [IOP]) and age‐related macular degeneration (AMD).
Methods
Baseline and 3‐year follow‐up data from the 30 097 participants of the Canadian Longitudinal Study on Aging were used. The follow‐up rate was 92%. QUARTZ, a deep learning algorithm, was used to extract data from retinal images including arteriolar and venular diameter, tortuosity and vertical CDR. Glaucoma and AMD were self‐reported. IOP was measured. Multiple linear and logistic regression were used to adjust for demographic, lifestyle and clinical factors.
Results
Having wider arterioles was associated with a lower odds of glaucoma (OR = 0.36, 95% CI: 0.20, 0.65) at baseline but there was no association using longitudinal data. Instead, glaucoma at baseline was strongly associated with 3‐year change in arteriolar diameter (β = −0.21, 95% CI: −0.37, −0.05) indicating that the cross‐sectional association may have been due to reverse causality. Using longitudinal data, greater venular tortuosity was associated with a reduced 3‐year development of glaucoma (OR = 0.52, 95% CI: 0.31, 0.87) and a 3‐year reduction in the CDR (β = −0.006, 95% CI: −0.010, −0.002). Wider venular diameter was associated with a higher odds of AMD at baseline (OR = 2.77, 95% CI: 1.50, 5.15) and a higher odds of the 3‐year development of AMD (OR = 4.15, 95% CI: 1.95, 8.82).
Conclusions
Understanding the temporal relationship of changes in the retinal microvasculature and the development of eye disease may lead to better treatment and prevention strategies
Electronic medicine management systems in developing countries: A landscape review
Get PDFMedicines are a major global health expense. However, suboptimal use increases costs and causes patient harm. One way to reduce costs and increase safe, efficient medicines use is with electronic medicines management systems (EMMS). They allow easy capture of routine health data which can facilitate research, service planning and reimbursement processes. There are various barriers to healthcare digitization in developing countries (DCs), although some have overcome these. We sought to understand the landscape of EMMS use in DCs. We systematically searched six bibliographic databases from inception to 23 October 2024 for studies reporting the implementation and/or use of EMMS in countries with lower than ‘very high’ Human Development Index (HDI). We qualitatively and quantitatively summarized data on geographic location, healthcare setting and system functionality. We created an interactive map illustrating spatial and temporal trends in EMMS use. A total of 314 records described the use of EMMS in 45 DCs, 206 of which described coexistence/integration of other health data (e.g., electronic health records [EHR]). Predominantly, EMMS were for prescribing (n = 264) or dispensing (n = 66), implemented in secondary care settings and operated locally rather than regionally or nationally. Common EMMS use‐cases included adherence monitoring in human immunodeficiency virus (HIV) and tuberculosis treatment. Our findings highlight both widespread EMMS adoption—commonly in the context of a broader EHR—and persistent gaps in implementation. These insights could be used by policymakers and healthcare leaders to guide strategy and funding decisions. Existing systems could be leveraged for service planning, healthcare delivery and optimizing medicine use. Where EMMS are not yet in use, our findings provide a roadmap for stakeholders to identify and emulate successful implementations in similar healthcare settings. Expanding the interoperability and scale of EMMS could further enable transformative digital technologies, increasing efficiencies and coverage, and ultimately improving patient outcomes
Estimating road vehicle speed from high-resolution satellite imagery for environmental applications: A case study of Barcelona
Get PDFData on road traffic speeds is needed for air and environmental noise pollution modelling, for regulatory control, exposure assessment and assessing health impacts. However, vehicle speed data is often not available and national speed limits, by road classification, may be used as a proxy instead. This may contribute to uncertainties in model predictions. This study presents novel methods, applied to satellite imagery, to calculate vehicle speed road by road for entire cities, demonstrating their use in Barcelona. The approach exploits the fraction of a second gap between eight multi-spectral sensors onboard the WorldView-2 and -3 satellites and was used to estimated speeds for 128,206 vehicles on motorways, trunk, primary, secondary and tertiary roads from 10 satellite images. The average estimated vehicle speeds ranged from 69 km/h on motorways to 31 km/h on tertiary roads. Satellite-derived vehicle speeds showed good agreement with Directions API speeds on a subset of roads (R2 = 0.71, NMGE = 0.23 and RMSE 13.4 km/h). A Normalised Mean Bias of 0.04 suggests that on average the satellite and Directions API estimates were similar. Using Directions API as the benchmark, satellite-derived estimated speeds yielded values of RMSE of 13.4 km/h, compared with and RMSE of 25.7 km/h using road type national speed limits, for a subset of roads. In this pilot study, therefore, satellite-derived vehicle speeds yield a 48% reduction in error over using the national speed limit by road type. This paper shows that high-resolution satellite imagery has potential to quantify vehicle speed in cities
Inhibition of Soluble Epoxide Hydrolase Reduces Inflammation and Myocardial Injury in Arrhythmogenic Cardiomyopathy
Get PDFWe analyzed the role of pro- and anti-inflammatory eicosanoids in the pathogenesis of arrhythmogenic cardiomyopathy (ACM). Lipidomics revealed reduced levels of anti-inflammatory oxylipins in plasma and increased levels of pro-inflammatory eicosanoids in hearts of Dsg2mut/mut mice, a preclinical model of ACM. Disease features were reversed in vitro in rat ventricular myocytes expressing mutant JUP by the anti-inflammatory epoxyeicosatrienoic acid 14-15-EET, whereas 14,15-EEZE, which antagonizes the 14,15-EET receptor, intensified nuclear accumulation of the desmosomal protein plakoglobin. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that converts anti-inflammatory EETs into polar, less active diols, prevented progression of myocardial injury in Dsg2mut/mut mice and promoted recovery of contractile function. This was associated with reduced myocardial expression of genes involved in innate immune signaling and fewer injurious macrophages expressing CCR2. These results suggest that pro-inflammatory eicosanoids contribute to the pathogenesis of ACM. Inhibition of sEH may be an effective, mechanism-based therapy for ACM patients
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