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Accelerated multi-shell diffusion MRI with Gaussian process estimated reconstruction of multi-band imaging
No full textPurpose: This work aims to propose a robust reconstruction method exploiting shared information across shells to increase the acquisition speed of multi-shell diffusion MRI, enabling rapid tissue microstructure mapping.
Theory and Methods: Local q-space points share similar information. Gaussian Process can exploit the q-space smoothness in a data-driven way and provide q-space signal estimation based on the signals from a q-space neighborhood. The Diffusion Acceleration with Gaussian process Estimated Reconstruction (DAGER) method uses the signal estimation from Gaussian process as a prior in a joint k-q reconstruction and improves image quality under high acceleration factors compared to conventional (k-only) reconstruction. In this work, we extend the DAGER method by introducing a multi-shell covariance function and correcting for Rician noise distribution in magnitude data when fitting the Gaussian process model. The method was evaluated with both simulation and in vivo data.
Results:> Simulated and in-vivo results demonstrate that the proposed method can significantly improve the image quality of reconstructed dMRI data with high acceleration both in-plane and slice-wise, achieving a total acceleration factor of 12. The improvement of image quality allows more robust diffusion model fitting compared to conventional reconstruction methods, enabling advanced multi-shell diffusion analysis within much shorter scan time.
Conclusion: The proposed method enables highly accelerated dMRI which can shorten the scan time of multi-shell dMRI without sacrificing quality compared to conventional practice. This may facilitate a wider application of advanced dMRI models in basic and clinical neuroscience
Atmospheric mineral dust emission and climatological variables for Etosha Pan, Namibia (2000-2022)
No full textCSV data files containing records of mineral dust plume events (dust point source locations lat/long, start and end time, duration, plume movement direction, and sensor used for detection), extrapolated monthly, seasonal and annual dust plume event and dust days (i.e. count of days in which a dust plume was observed) and dust optical depth (DOD) data, and associated records of meteorological and hydrological variables for dust plume events (i.e. 10 m wind speed, lake area extents, catchment precipitation totals and specific source point surface wetting frequencies by precipitation and ephemeral flooding, and El Niño Southern Oscillation [ENSO 3.4] and South Indian Ocean Dipole [SIOD] index values) for Etosha Pan, Namibia for the analysis period from July 1999 to January 2023.
All datasets are readable using CSV file viewer software.
Dust plume event data were analysed manually by the author Natasha S. Wallum. Data used for detection were sourced from Terra and Aqua satellites MODIS level 1b and Aerosol data acquired from the Atmospheric Archive and Distribution System (LAADS) Distributed Active Archive Center (DAAC), located in the Goddard Space Flight Center in Greenbelt, Maryland (https://ladsweb.nascom.nasa.gov/) and SEVIRI data procured from the EUMETSAT Data Store (https://data.eumetsat.int/search?query=). Analysis of SEVIRI imagery utilised the Clear Sky Differencing (CSD) algorithm developed by Jon Murray and colleagues (https://agupubs.onlinelibrary.wiley.com/doi/full/10.1002/2016JD025221).
Lake area extent data were derived by density thresholding of near-infrared (NIR) reflectance data from the MODIS Terra satellite obtained from NASA’s LAADS DAAC data portal (https://ladsweb.modaps.eosdis.nasa.gov/) and verified using Level-2 (8-day) images collected from Landsat 5 TM (1984–2012) and Landsat 8 OLI (2013 – present day) sensors were acquired through the USGS Earth Explorer data portal (www.earthexplorer.com).
The contributing catchment (Cuvelai-Etosha Basin) was derived from the HydroBASINS (Lehner and Grill, 2013) catchment database (https://hydrosheds.org/products/hydrobasins), and this area was used to derive daily precipitation inputs for 2000–2022 (July – June hydrological year) from The Integrated Multi-Satellite Retrievals for GPM (GPM-IMERG) and The Tropical Rainfall Measuring Mission (TRMM) gridded time-series of precipitation available from the Goddard Earth Science Data and Information Services Center (http://disc.gsfc.nasa.gov/).
These data were augmented by limited monthly precipitation records (2000–2022) from 10 local weather stations (Mahenene, Ondjiva, Namacunde, Oshaambelo, Ogongo, Ondangwa, Okashana, Okapya, Okaukuejo, and Mannheim) provided by the Southern African Science Service Centre for Climate Change and Adaptive Land Management (SASSCAL; https://sasscal.org/) and continuous rain gauge measurements recorded at Windpoort located in close proximity to Etosha Pan within the Cuvelai-Etosha Basin.
Near-surface (10 m) wind speeds (m/s) and cubed wind speed anomaly data were derived from ERA5-Land reanalysis model data product available from the Copernicus Climate Change Service Data Store (https://cds.climate.copernicus.eu/).
Surface wetting frequencies and time since wetting for dust event source points were calculated by the author Natasha S. Wallum using ArcGIS Pro (education licence on behalf of the University of Oxford).
Global climate indices of SST anomalies data (ENSO 3.4 and SIOD) were obtained from the Climate Diagnostics Centre (CDC) online archives (http://psl.noaa.gov/data/climateindices) and the Indian Ocean dipole (IOD) site maintained by the Frontier Research System for Global Change (FRSGC)/Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Climate Variations Research Program (http://www.jamstec.go.jp)
Predicting intra-abdominal hypertension using anthropometric measurements and machine learning
Get PDFAlmost one in four critically ill patients suffer from intra-abdominal hypertension (IAH). Currently, the gold standard for measuring intra-abdominal pressure (IAP) is via the bladder. Measurement of IAP is important to identify IAH early and thus implement appropriate management in order to avoid complications. It may be possible to use anthropometric parameters to predict IAP and thus identify IAH non-invasively. This retrospective observational study investigated how the most relevant body parameters evolve in relation to IAP, and whether IAP can be predicted based on anthropometric parameters. The IAP and 28 body parameters of 96 critically ill patients were recorded. Following statistical analyses such as Pearson’s and mutual information correlation, the collected data were used to train a simulation model to examine reliable relationships between IAP, predict IAP values, and detect IAH. Three metrics were shown to sufficiently predict intra-bladder pressure (IBP) with a Pearson’s correlation of 0.75 (R2 = 0.56). These parameters are the difference between the convex and horizontal xiphoid-to-pubis distance, sagittal abdominal diameter, and abdominal compliance. Subsequently, we found 1 metric that is able to predict the presence of IAH with Pearson correlation of 0.89 (R2 = 0.79). This metric is the difference between the convex and horizontal xiphoid to pubis distance. Three measured body parameters showed a correlation of more than 50% with IBP and they are sufficient for a reliable prediction of IBP, however, IAH can be most reliably predicted based on the difference between the convex and horizontal xiphoid-pubis distance and sagittal abdominal diameter. Future studies with larger patient populations and diverse body shapes are warranted to confirm these findings
Qualitative insights into planning implementation of FeNO-guided asthma management in primary care
Get PDFFractional exhaled nitric oxide (FeNO) testing is used in primary care in some areas of the UK to aid asthma diagnosis but is used less frequently for managing asthma. A randomised controlled trial (RCT) is investigating whether an intervention, including FeNO testing and a clinical algorithm, improves outcomes for patients with asthma. This study was conducted to explore potential for implementation of the intervention. The study aim was to explore views of those with a vested interest in implementing the FeNO intervention into primary care asthma reviews. In-depth, semi-structured interviews were conducted online with individuals, including those with experience in policymaking, healthcare management, National Health Service commissioning, as healthcare professionals (HCPs) with extended roles, and patients and advocates. Inductive thematic analysis was conducted for nineteen interviews. Findings suggest complex interplay of barriers, contextual issues and facilitators. Overall, participants perceived FeNO-informed asthma management would enhance care, if used appropriately and flexibly according to context, for example planning implementation alongside remote reviews. Easier, equitable access to funded FeNO equipment would be needed for national implementation. Participants suggested motivation of all involved in future implementation may be increased by guidelines recommending FeNO, and by use of financial incentives and champions sharing best practice examples. In conclusion, financial obstacles were reiterated as a primary barrier to FeNO use. Despite barriers, facilitating implementation by harnessing prominent cost-benefits could persuade decision makers and clinicians. Findings lay early foundations for development of an implementation strategy
Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia
Get PDFMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Syndrome (GWS), and Fibromyalgia (FM) are complex, chronic illnesses with overlapping clinical features. Symptoms that are reported across these conditions include post-exertional malaise (PEM), fatigue, and pain, yet the etiology of these illnesses remains largely unknown. Diagnosis is challenging in patients with these conditions as definitive biomarkers are lacking; patients are required to meet clinical criteria and often undergo lengthy testing to exclude other conditions, a process that is often prolonged, costly, and burdensome for patients. The identification of reliable validated biomarkers could facilitate earlier and more accurate diagnosis and drive the development of targeted pharmacological therapies that might address the underlying pathophysiology of these diseases. Major driving forces for biomarker identification are the advancing fields of metabolomics and proteomics that allow for comprehensive characterization of metabolites and proteins in biological specimens. Recent technological developments in these areas enable high-throughput analysis of thousands of metabolites and proteins from a variety of biological samples and model systems, that provides a powerful approach to unraveling the metabolic phenotypes associated with these complex diseases. Emerging evidence suggests that ME/CFS, GWS, and FM are all characterized by disturbances in metabolic pathways, particularly those related to energy production, lipid metabolism, and oxidative stress. Altered levels of key metabolites in these pathways have been reported in studies highlighting potential common biochemical abnormalities. The precise mechanisms driving altered metabolic pathways in ME/CFS, GWS, and FM remain to be elucidated; however, the elevated oxidative stress observed across these illnesses may contribute to symptoms and offer a potential target for therapeutic intervention. Investigating the mechanisms, and their role in the disease process, could provide insights into disease pathogenesis and reveal novel treatment targets. As such, comprehensive metabolomic and proteomic analyses are crucial for advancing the understanding of these conditions in-order to identify both common, and unique, metabolic alterations that could serve as diagnostic markers or therapeutic targets
Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis
Get PDFRed blood cell development from erythroid progenitors requires profound reshaping of metabolism and gene expression. How these transcriptional and metabolic alterations are coupled is unclear. Nprl3 (an inhibitor of mTORC1) has remained in synteny with the α-globin genes for >500 million years, and harbours most of the a-globin enhancers. However, whether Nprl3 serves an erythroid role is unknown. We found that while haematopoietic progenitors require basal Nprl3 expression, erythroid Nprl3 expression is further boosted by the α-globin enhancers. This lineage-specific upregulation is required for sufficient erythropoiesis. Loss of Nprl3 affects erythroblast metabolism via elevating mTORC1 signalling, suppressing autophagy and disrupting glycolysis. Broadly consistent with these murine findings, human NPRL3-knockout erythroid progenitors produce fewer enucleated cells and demonstrate dysregulated mTORC1 signalling in response to nutrient availability and erythropoietin. Therefore, we propose that the anciently conserved linkage of NprI3, α-globin and their associated enhancers has coupled metabolic and developmental control of erythropoiesis
Streamlined and efficient genome editing in Cupriavidus necator H16 using an optimised SIBR-Cas system
Get PDFCupriavidus necator H16 is a promising microbial platform strain for CO2 valorisation. While C. necator is amenable to genome editing, existing tools are often inefficient or rely on lengthy protocols, hindering its rapid transition to industrial applications. In this study, we simplified and accelerated the genome editing pipeline for C. necator by harnessing the Self-splicing Intron-Based Riboswitch (SIBR) system. We used SIBR to tightly control and delay Cas9-based counterselection, achieving >80% editing efficiency at two genomic loci within 48 hours after electroporation. To further increase the versatility of the genome editing toolbox, we upgraded SIBR to SIBR2.0 and used it to regulate the expression of Cas12a. SIBR2.0-Cas12a could mediate gene deletion in C. necator with ~70% editing efficiency. Overall, we streamlined the genome editing pipeline for C. necator, facilitating its potential role in the transition to a bio-based economy
Tuberculosis preventive therapy: scientific and ethical considerations for trials of ultra-short regimens
No full textPreventive therapy remains key to the elimination of tuberculosis and is typically offered to people with presumptive Mycobacterium tuberculosis infection to prevent active disease. Although the duration of tuberculosis preventive therapy has been reduced substantially over time, it remains long in absolute terms, and uptake remains low. Treatment-shortening trials using non-inferiority designs have so far led to the implementation of effective regimens of 1–4 months’ duration. Such regimens are a substantial improvement on the previous 6–9 months’ duration standard of care but still far too long given potential toxicity and the very low baseline risk of disease for most individuals. The efficacy of even shorter tuberculosis preventive therapy regimens, including ultra-short regimens shorter than 2 weeks’ duration, is yet to be explored, but optimal public health outcomes might be achieved even if the efficacy of such regimens is lower than that of the standard of care. Greater acceptability could lead to higher population uptake, and, potentially, to more cases of tuberculosis avoided. Nonetheless, the optimal duration of ultra-short tuberculosis preventive therapy regimens cannot be explored through classic two-arm non-inferiority trials. Instead, the relationship between different durations and efficacy of tuberculosis preventive therapy will need to be characterised, requiring some participants to be randomly assigned to no (or delayed) therapy in order to characterise the number of tuberculosis cases averted by the shortest options. We argue that such trials are needed to identify the optimal trade-off between efficacy and acceptability and would be ethically acceptable provided there were appropriate risk mitigation measures for participants, including careful monitoring for the development of active disease. In this Personal View, we discuss some of the scientific and ethical considerations around the investigation of ultra-short-course preventive therapy for tuberculosis
Effects of intensive blood pressure treatment on orthostatic hypertension: individual level meta-analysis
Get PDFObjective: To determine the effects of intensive blood pressure treatment on orthostatic hypertension. Design: Systematic review and individual participant data meta-analysis. Data sources: MEDLINE, Embase, and Cochrane CENTRAL databases through 13 November 2023. Inclusion criteria: Population: ≥500 adults, age ≥18 years with hypertension or elevated blood pressure; intervention: randomized trials of more intensive antihypertensive drug treatment (lower blood pressure goal or active agent) with duration ≥6 months; control: less intensive antihypertensive drug treatment (higher blood pressure goal or placebo); outcome: measured standing blood pressure. Main outcomes: Orthostatic hypertension, defined as an increase in systolic blood pressure ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg after changing from sitting to standing. Data synthesis: Two investigators independently abstracted articles. Individual participant data from nine trials identified during the systematic review were appended together as a single dataset. Results: Of 31 124 participants with 315 497 standing blood pressure assessments, 9% had orthostatic hypotension (that is, a drop in blood pressure after standing of systolic ≥20 mm Hg or diastolic ≥10 mm Hg), 17% had orthostatic hypertension, and 3.2% had both a rise in systolic blood pressure and standing blood pressure ≥140 mm Hg at baseline. The effects of more intensive treatment were similar across trials with odds ratios for orthostatic hypertension ranging from 0.85 to 1.08 (I2=38.0%). During follow-up, 17% of patients assigned to more intensive treatment had orthostatic hypertension, whereas 19% of those assigned less intensive treatment had orthostatic hypertension. Compared with less intensive treatment, the risk of orthostatic hypertension was lower with more intensive blood pressure treatment (odds ratio 0.93, 95% confidence interval 0.90 to 0.96). Effects were greater among non-black versus black adults (odds ratio 0.86 v 0.97; P for interaction=0.003) and adults without diabetes versus those with diabetes (0.88 v 0.96; P for interaction=0.05) but did not differ by age ≥75 years, sex, baseline seated blood pressure ≥130/≥80 mm Hg, obesity, stage 3 kidney disease, stroke, cardiovascular disease, standing systolic blood pressure ≥140 mm Hg, or pre-randomization orthostatic hypertension (P for interactions ≥0.05). Conclusions: In this pooled cohort of adults with elevated blood pressure or hypertension, orthostatic hypertension was common and more intensive blood pressure treatment modestly reduced the occurrence of orthostatic hypertension. These findings suggest that approaches generally used for seated hypertension may also prevent hypertension on standing. Study registration: Prospero CRD42020153753 (original proposal)
A reflexive thematic analysis of existential losses in men with osteoporosis: “I’m not the person I was somehow … although I am”
Get PDFBackground: Osteoporosis is a global health concern that is likely to increase with a rapidly ageing world population. It affects one in three women and one in five men over the age of 50. Although there is a large body of qualitative research exploring the experience of living with osteoporosis, far fewer studies have focused on men. We aimed to explore the experiences of men with osteoporotic vertebral fracture. Methods: We interviewed 13 White British men aged 63 to 94 with an osteoporotic vertebral fracture. We used the six stages of reflexive thematic analysis: familiarisation with the data; coding; generating initial themes; developing and reviewing themes through discussion; refining and naming themes; writing up. Results: We developed six themes giving insight into the existential losses of men with osteoporosis: I have felt a step change coming; I regret that I am no longer the person I once was; it is demeaning (but others are worse off than me); I need to know where I am heading; I need to understand why me; I need to feel like I am in someone’s hands. We describe moral narratives used in defence of self. Conclusions: Our findings highlight the challenge of deciphering the symptoms of osteoporosis and age-related changes. We also see the impact on self and a struggle to repair self. Healthcare providers are in a unique and privileged position to accompany their patients at points of existential crisis. As such, they attend to the repair of both identity and body. This comes with an ethical responsibility and has implications for clinical education. Health professionals should feel equipped to be alongside people facing existential losses. Qualitative research can give valuable insight into the phenomenology of illness and contribute to improvements in care pathways