Mechanistic simulations of kelp populations in a dynamic landscape of light, temperature, and winter storms

\ua9 2023 The Author(s). Kelp forests are widely distributed across the coastal ocean, support high levels of biodiversity and primary productivity, and underpin a range of ecosystem services. Laminaria hyperborea is a forest-forming kelp species in the Northeast Atlantic that alters the local environment, providing biogenic structure for a diversity of associated organisms. Populations are strongly affected by light availability, temperature, and storm-related disturbance. We constructed a stage-based, two-season model of L. hyperborea populations along the coast of Great Britain and Ireland to predict biomass across a range of depths, drawing on extensive surveys and data from the literature. Population dynamics were driven by wave exposure, historic winter storm intensity, and simulated interannual variation in temperature and depth-attenuated light intensity, with density-dependent competition for light and space. High biomass was predicted in shallow depths across the domain on suitable substrate, with populations extending deeper in the north and west where light penetration was greater. Detritus production was heavily skewed across years, particularly at greater depths, with 10 % of years comprising more than 50 % of detritus on average below 10 m depth. Annual fluctuations in light and storm intensity produced opposing population oscillations with a ∼6-year period persisting for up to a decade but diminishing sharply with depth. Interannual variation in temperature had minimal impact. Biomass was most sensitive to survival and settlement rates, with negligible sensitivity to individual growth rates. This model highlights the need for an improved understanding of canopy and subcanopy mortality, particularly regarding increasingly frequent heatwaves. Estimations of kelp forest contributions to carbon sequestration should consider the high variability among years or risk underestimating the potential value of kelp forests. Process-based simulations of populations with realistic spatiotemporal environmental variability are a valuable approach to forecasting biotic responses to an increasingly extreme climate

Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells.

In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.Research in the S.P.J. laboratory is funded by Cancer Research UK (CRUK; programme grant C6/A11224), the European Research Council and the European Community Seventh Framework Programme (grant agreement no. HEALTH-F2-2010-259893; DDResponse). Core funding is provided by Cancer Research UK (C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives salary from the University of Cambridge, supplemented by CRUK. J.V.F. was funded by Cancer Research UK programme grant C6/A11224 and the Ataxia Telangiectasia Society. J.C. was funded by Cancer Research UK programme grant C6/A11224. D.J.A. is supported by CRUK. Research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) and ERC grant agreement no. (311166)

Modified Harmonic Reduction Pulse Width Modulation (mHRPWM) for Switched Excitation of Resonant HIFU Transducers

High Intensity Focused Ultrasound (HIFU) is reliant on carefully designed excitation systems capable of high power, and low distortion. The use of array transducers additionally requires amplitude control for apodization and attenuation compensation plus phase control for inter element timing for beamstearing, focusing and correction. Power amplifiers possess all the required characteristics except they can be expensive and bulky thus placing barriers to adoption especially for large channel count arrays. Switched mode excitation systems are capable of fulfilling all requirements except minimizing distortion can be problematic due to the lack of availability of suitably high speed MOSFETs placing restrictions of waveform design. This work presents an modification to the Harmonic Reduction Pulse Width Modulation (HRPWM) method specifically designed to minimize harmonic distortion in systems constrained by MOSFET performance in HIFU excitation systems. The proposed method is of significance as the use of external filtering and transformer coupling of the excitation waveform is not required. The proposed method is demonstrated through experimental hydrophone testing with a 1.1 MHz HIFU transducer and demonstrates the successful generation of excitation waveforms with continuously variable amplitude control and low third harmonic output

HIFU Power Monitoring Using Combined Instantaneous Current and Voltage Measurement

During HIFU therapy it is important that the electrical power delivered to the transducer is monitored to avoid under or over exposure, ensure patient safety and to protect the transducer itself. Due to ease of measurement, the transducer’s potential difference may be as an indicator of power delivery. However, even when a transducer’s complex impedance is well characterised at small amplitudes and matching networks are used, voltage-only (VO) monitoring cannot account for the presence of drive waveform distortion, changes to the acoustic path or damage to the transducer. In this study, combined current and voltage (CCV) is proposed as an MRI-compatible, miniature alternative to bi-directional power couplers that is compatible with switched amplifiers. For CCV power measurement, current probe data was multiplied by the voltage waveform and integrated in the frequency domain. Transducer efficiency was taken into account to predict acoustic power. The technique was validated with a radiation force balance (RFB). When using a typical HIFU transducer and amplifier, VO predictions and acoustic power had a maximum difference of 20%. However, under the same conditions, CCV only had a maximum difference of 5%. The technique was applied to several lesioning experiments and it was shown that when VO was used as a control between two amplifiers there was up to a 38% difference in lesion area. This greatly reduced to a maximum of 5% once CCV was used instead. These results demonstrate that CCV can accurately predict real-time electrical power delivery leading to safer HIFU treatments

Mechanistic simulations of kelp populations in a dynamic landscape of light, temperature, and winter storms

Kelp forests are widely distributed across the coastal ocean, support high levels of biodiversity and primary productivity, and underpin a range of ecosystem services. Laminaria hyperborea is a forest-forming kelp species in the Northeast Atlantic that alters the local environment, providing biogenic structure for a diversity of associated organisms. Populations are strongly affected by light availability, temperature, and storm-related disturbance. We constructed a stage-based, two-season model of L. hyperborea populations along the coast of Great Britain and Ireland to predict biomass across a range of depths, drawing on extensive surveys and data from the literature. Population dynamics were driven by wave exposure, historic winter storm intensity, and simulated interannual variation in temperature and depth-attenuated light intensity, with density-dependent competition for light and space. High biomass was predicted in shallow depths across the domain on suitable substrate, with populations extending deeper in the north and west where light penetration was greater. Detritus production was heavily skewed across years, particularly at greater depths, with 10 % of years comprising more than 50 % of detritus on average below 10 m depth. Annual fluctuations in light and storm intensity produced opposing population oscillations with a ∼6-year period persisting for up to a decade but diminishing sharply with depth. Interannual variation in temperature had minimal impact. Biomass was most sensitive to survival and settlement rates, with negligible sensitivity to individual growth rates. This model highlights the need for an improved understanding of canopy and subcanopy mortality, particularly regarding increasingly frequent heatwaves. Estimations of kelp forest contributions to carbon sequestration should consider the high variability among years or risk underestimating the potential value of kelp forests. Process-based simulations of populations with realistic spatiotemporal environmental variability are a valuable approach to forecasting biotic responses to an increasingly extreme climat

Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children

Alzheimer's pathology targets distinct memory networks in the ageing brain

Alzheimer’s disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer’s disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-β deposition in the progression from ageing to Alzheimer’s disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20–93 years; 47 amyloid-β-positive) and 20 amyloid-β-positive patients with mild cognitive impairment or Alzheimer’s disease dementia (65–95 years). Tau burden was relatively higher in anterior-temporal regions in normal ageing and this difference was further pronounced in the presence of amyloid-β and cognitive impairment, indicating exacerbation of ageing-related processes in Alzheimer’s disease. In contrast, amyloid-β deposition dominated in posterior-medial regions. A subsample of 50 cognitively normal older (26 amyloid-β-positive) and 25 young adults performed an object and scene memory task while functional MRI data were acquired. Group comparisons showed that tau-positive (n = 18) compared to tau-negative (n = 32) older adults showed lower mnemonic discrimination of object relative to scene images [t(48) = −3.2, P = 0.002]. In a multiple regression model including regional measures of both pathologies, higher anterior-temporal flortaucipir (tau) was related to relatively worse object performance (P = 0.010, r = −0.376), whereas higher posterior-medial PiB (amyloid-β) was related to worse scene performance (P = 0.037, r = 0.309). The functional MRI data revealed that tau burden (but not amyloid-β) was associated with increased task activation in both systems and a loss of functional specificity, or dedifferentiation, in posterior-medial regions. The loss of functional specificity was related to worse memory. Our study shows a regional dissociation of Alzheimer’s disease pathologies to distinct memory networks. While our data are cross-sectional, they indicate that with ageing, tau deposits mainly in the anterior-temporal system, which results in deficits in mnemonic object discrimination. As Alzheimer’s disease develops, amyloid-β deposits preferentially in posterior-medial regions additionally compromising scene discrimination and anterior-temporal tau deposition worsens further. Finally, our findings propose that the progression of tau pathology is linked to aberrant activation and dedifferentiation of specialized memory networks that is detrimental to memory function

Prevalence and effects of emphysema in never-smokers with rheumatoid arthritis interstitial lung disease

AIMS: Autoimmune conditions such as rheumatoid arthritis-related interstitial lung disease (RA-ILD) have been linked to the existence of emphysema in never-smokers. We aimed to quantify emphysema prevalence in RA-ILD never-smokers and investigate whether combined pulmonary fibrosis and emphysema (CPFE) results in a worsened prognosis independent of baseline disease extent. METHODS: RA-ILD patients presenting to the Royal Brompton Hospital (n=90) and Asan Medical Center (n=155) had CT's evaluated for a definite usual interstitial pneumonia (UIP) pattern, and visual extents of emphysema and ILD. RESULTS: Emphysema, identified in 31/116 (27%) RA-ILD never-smokers, was associated with obstructive functional indices and conformed to a CPFE phenotype: disproportionate reduction in gas transfer (DLco), relative preservation of lung volumes. Using multivariate logistic regression, adjusted for patient age, gender and ILD extent, emphysema presence independently associated with a CT-UIP pattern in never-smokers (0.009) and smokers (0.02). On multivariate Cox analysis, following adjustment for patient age, gender, DLco, and a CT-UIP pattern, emphysema presence (representing the CPFE phenotype) independently associated with mortality in never-smokers (p=0.04) and smokers (p<0.05). CONCLUSION: 27% of RA-ILD never-smokers demonstrate emphysema on CT. Emphysema presence in never-smokers independently associates with a definite CT-UIP pattern and a worsened outcome following adjustment for baseline disease severity

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

Differential Item Functioning in PISA Due to Mode Effects

One of the most important goals of the Programme for International Student Assessment (PISA) is assessing national changes in educational performance over time. These so-called trend results inform policy makers about the development of ability of 15-year-old students within a specific country. The validity of those trend results prescribes invariant test conditions. In the 2015 PISA survey, several alterations to the test administration were implemented, including a switch from paper-based assessments to computer-based assessments for most countries (OECD 2016a). This alteration of the assessment mode is examined by evaluating if the items used to assess trends are subject to differential item functioning across PISA surveys (2012 vs. 2015). Furthermore, the impact on the trend results due to the change in assessment mode of the Netherlands is assessed. The results show that the decrease reported for mathematics in the Netherlands is smaller when results are based upon a separate national calibration.</p