A biologically relevant rapid quantification of physical and biological stress profiles on rocky shores.

Different combinations and intensities of physical (e.g. thermal) and biological (e.g.competition or predation) stress operate on organisms in different locations. Variation in these stresses can occur over small to medium spatial scales (cm to 10s m) in heterogeneous environments such as rocky shores, due to differences in sun and wave exposure, shore topography and/or recruitment. In this study we demonstrate how simple measurements can be taken that represent physical and biological stresses (stress profiles)in a given location. Using a bootstrapped principal component analysis, we identified significantly different stress profiles at four sites separated by only 10s to 100s of metres on the Shek O peninsula in Hong Kong. We then measured response to thermal stress, as determined by detachment temperature, in the limpet Cellana grata (which is known to be a sensitive indicator species to thermal stress) from each location. Significant differences in stress profile between locations were also seen in thermal stress tolerance of limpets from those locations. At locations where the major stresses are likely to be more physical or less biological in nature (e.g. southerly facing aspect or lower density of grazers), the mean detachment temperature was higher, whereas detachment temperature was lower at sites with more biological or less physical stress. This method is, therefore, able to determine biologically meaningful differences in stress profiles over small to medium spatial scales, and demonstrates that localised adaptation (i.e. post planktonic settlement) or acclimation of species may occur in response to these different stress profiles. The technique can be adapted to different environments and smaller or larger spatial scales as long as the stress experienced by the study species is relevant to these scales

Multi-Channel Signal Generator ASIC for Acoustic Holograms

A CMOS application-specific integrated circuit (ASIC) has been developed to generate arbitrary, dynamic phase patterns for acoustic hologram applications. An experimental prototype has been fabricated to demonstrate phase shaping. It comprises a cascadable 1 × 9 array of identical, independently-controlled signal generators implemented in a 0.35 μ m minimum feature size process. It can individually control the phase of a square wave on each of the nine output pads. The footprint of the integrated circuit is 1175 × 88 μ m2. A 128 MHz clock frequency is used to produce outputs at 8 MHz with phase resolution of 16 levels (4-bit) per channel. A 6 × 6 air-coupled matrix array ultrasonic transducer was built and driven by four ASICs, with the help of commercial buffer amplifiers, for the application demonstration. Acoustic pressure mapping and particle manipulation were performed. Additionally, a 2 × 2 array piezoelectric micromachined ultrasonic transducer (PMUT) was connected and driven by four output channels of a single ASIC, demonstrating the flexibility of the ASIC to work with different transducers and the potential for direct integration of CMOS and PMUTs

Variability of radiation doses of cardiac diagnostic imaging tests: the RADIO-EVINCI study (RADIationdOse subproject of the EVINCI study)

Background: Patients with coronary artery disease can accumulate significant radiation dose through repeated exposures to coronary computed tomographic angiography, myocardial perfusion imaging with single photon emission computed tomography or positron emission tomography, and to invasive coronary angiography. Aim of the study was to audit radiation doses of coronary computed tomographic angiography, single photon emission computed tomography, positron emission tomography and invasive coronary angiography in patients enrolled in the prospective, randomized, multi-centre European study–EVINCI (Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease).Methods: We reviewed 1070 tests (476 coronary computed tomographic angiographies, 85 positron emission tomographies, 310 single photon emission computed tomographies, 199 invasive coronary angiographies) performed in 476 patients (mean age 60 ± 9 years, 60% males) enrolled in 12 centers of the EVINCI. The effective doses were calculated in milli-Sievert (mSv) as median, interquartile range (IQR) and coefficient of variation of the mean.Results: Coronary computed tomographic angiography (476 exams in 12 centers) median effective dose was 9.6 mSv (IQR = 13.2 mSv); single photon emission computed tomography (310 exams in 9 centers) effective dose was 9.3 (IQR = 2.8); positron emission tomography (85 in 3 centers) effective dose 1.8 (IQR = 1.6) and invasive coronary angiography (199 in 9 centers) effective dose 7.4 (IQR = 7.3). Inter-institutional variability was highest for invasive coronary angiography (100%) and coronary computed tomographic angiography (54%) and lowest for single photon emission computed tomography (20%). Intra-institutional variability was highest for invasive coronary angiography (121%) and coronary computed tomographic angiography (115%) and lowest for single photon emission computed tomography (14%).Conclusion: Coronary computed tomographic angiography and invasive coronary angiography doses vary substantially between and within centers. The variability in nuclear medicine procedures is substantially lower. The findings highlight the need to audit doses, to track cumulative exposures and to standardize doses for imaging techniques.Trial registration: The study protocol is available at https://www.clinicaltrials.gov/ (ClinicalTrials.gov Identifier: NCT00979199). Information provided on September 16, 2009

Perceptions of and practical experience with the National Surveillance Centre in managing medicines availability amongst users within public healthcare facilities in South Africa : findings and implications

The introduction of the National Surveillance Centre (NSC) has improved the efficiency and effectiveness of managing medicines availability within the public healthcare system in South Africa. However, at present, there is limited data regarding the perceptions among users of the NSC and challenges that need addressing. A descriptive quantitative study was performed among all registered active NSC users between August and November 2022. Overall, 114/169 users responded to a custom-developed, self-administered questionnaire (67.5% response rate). Most respondents used the Stock Visibility System (SVS) National Department of Health (NDoH) (66.7% for medicines and 51.8% for personal protective equipment (PPE) or SVS COVID-19 (64.9% for COVID-19 vaccines) or RxSolution (57.0% manual report or 42.1% application programming interface (API)) for reporting medicines, PPE, and COVID-19 vaccines to the NSC and were confident in the accuracy of the reported data. Most respondents focused on both medicines availability and reporting compliance when accessing the NSC, with the integrated medicines availability dashboard and the COVID-19 vaccine dashboard being the most popular. The respondents believed the NSC allowed ease of access to data and improved data quality to better monitor medicines availability and use. Identified areas for improvement included improving internet connectivity, retraining some users, standardising the dashboards, adding more data points and reports, and expanding user adoption by increasing licence limits. Overall, this study found that the NSC in South Africa provides an effective solution for monitoring and improving medicines availability

Variability of radiation doses of cardiac diagnostic imaging tests: the RADIO-EVINCI study (RADIationdOse subproject of the EVINCI study)

Background: Patients with coronary artery disease can accumulate significant radiation dose through repeated exposures to coronary computed tomographic angiography, myocardial perfusion imaging with single photon emission computed tomography or positron emission tomography, and to invasive coronary angiography. Aim of the study was to audit radiation doses of coronary computed tomographic angiography, single photon emission computed tomography, positron emission tomography and invasive coronary angiography in patients enrolled in the prospective, randomized, multi-centre European study-EVINCI (Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease).Methods: We reviewed 1070 tests (476 coronary computed tomographic angiographies, 85 positron emission tomographies, 310 single photon emission computed tomographies, 199 invasive coronary angiographies) performed in 476 patients (mean age 60 +/- 9 years, 60% males) enrolled in 12 centers of the EVINCI. The effective doses were calculated in milli-Sievert (mSv) as median, interquartile range (IQR) and coefficient of variation of the mean.Results: Coronary computed tomographic angiography (476 exams in 12 centers) median effective dose was 9. 6 mSv (IQR = 13.2 mSv); single photon emission computed tomography (310 exams in 9 centers) effective dose was 9.3 (IQR = 2.8); positron emission tomography (85 in 3 centers) effective dose 1.8 (IQR = 1.6) and invasive coronary angiography (199 in 9 centers) effective dose 7.4 (IQR = 7.3). Inter-institutional variability was highest for invasive coronary angiography (100%) and coronary computed tomographic angiography (54%) and lowest for single photon emission computed tomography (20%). Intra-institutional variability was highest for invasive coronary angiography (121%) and coronary computed tomographic angiography (115%) and lowest for single photon emission computed tomography (14%).Conclusion: Coronary computed tomographic angiography and invasive coronary angiography doses vary substantially between and within centers. The variability in nuclear medicine procedures is substantially lower. The findings highlight the need to audit doses, to track cumulative exposures and to standardize doses for imaging techniques

The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

Objective: Barrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands. Methods: Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry. Results: Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell. Conclusions: Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus

Aspirin as an adjuvant treatment for cancer:feasibility results from the Add-Aspirin randomised trial

BACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer.METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment.FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants).INTERPRETATION: Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes.FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.</p

Expressions 1986

https://openspace.dmacc.edu/expressions/1007/thumbnail.jp

Current worldwide nuclear cardiology practices and radiation exposure: results from the 65 country IAEA Nuclear Cardiology Protocols Cross-Sectional Study (INCAPS)

Aims To characterize patient radiation doses from nuclear myocardial perfusion imaging (MPI) and the use of radiation-optimizing ‘best practices' worldwide, and to evaluate the relationship between laboratory use of best practices and patient radiation dose. Methods and results We conducted an observational cross-sectional study of protocols used for all 7911 MPI studies performed in 308 nuclear cardiology laboratories in 65 countries for a single week in March-April 2013. Eight ‘best practices' relating to radiation exposure were identified a priori by an expert committee, and a radiation-related quality index (QI) devised indicating the number of best practices used by a laboratory. Patient radiation effective dose (ED) ranged between 0.8 and 35.6 mSv (median 10.0 mSv). Average laboratory ED ranged from 2.2 to 24.4 mSv (median 10.4 mSv); only 91 (30%) laboratories achieved the median ED ≤ 9 mSv recommended by guidelines. Laboratory QIs ranged from 2 to 8 (median 5). Both ED and QI differed significantly between laboratories, countries, and world regions. The lowest median ED (8.0 mSv), in Europe, coincided with high best-practice adherence (mean laboratory QI 6.2). The highest doses (median 12.1 mSv) and low QI (4.9) occurred in Latin America. In hierarchical regression modelling, patients undergoing MPI at laboratories following more ‘best practices' had lower EDs. Conclusion Marked worldwide variation exists in radiation safety practices pertaining to MPI, with targeted EDs currently achieved in a minority of laboratories. The significant relationship between best-practice implementation and lower doses indicates numerous opportunities to reduce radiation exposure from MPI globall