Persistent Impact of Antenatal Maternal Anaemia on Child Brain Structure at 6-7 Years of Age: A South African Child Health Study.

Background The study aim was to determine whether associations of antenatal maternal anaemia with smaller corpus callosum, putamen, and caudate nucleus volumes previously described in children at age 2-3 years persist to age 6-7 years in the Drakenstein Child Health Study (DCHS). Methods This neuroimaging sub-study was nested within the DCHS, a South African population-based birth cohort. Pregnant women were enrolled (2012-2015) and mother-child dyads were followed prospectively. A sub-group of children had magnetic resonance imaging at 6-7 years of age (2018-2022). Mothers had haemoglobin measurements during pregnancy and a proportion of children were tested postnatally. Maternal anaemia (haemoglobin<11g/dL) and child anaemia were classified using WHO and local guidelines. Linear modeling was used to investigate associations between antenatal maternal anaemia status, maternal haemoglobin concentrations, and regional child brain volumes. Models included potential confounders and were conducted with and without child anaemia to assess the relative roles of antenatal versus postnatal anaemia. Results Overall, 157 children ( Mean [ SD ] age of 75.54 [4.77] months; 84 [53.50%] male) were born to mothers with antenatal haemoglobin data. The prevalence of maternal anaemia during pregnancy was 31.85% (50/157). In adjusted models, maternal anaemia status was associated with smaller volumes of the total corpus callosum (adjusted percentage difference, -6.77%; p =0.003), left caudate nucleus (adjusted percentage difference, -5.98%, p =0.005), and right caudate nucleus (adjusted percentage difference, -6.12%; p =0.003). Continuous maternal haemoglobin was positively associated with total corpus callosum ( ß =0.239 [CI: 0.10 to 0.38]; p <0.001) and caudate nucleus ( ß =0.165 [CI: 0.02 to 0.31]; p =0.027) volumes. In a sub-group ( n =89) with child haemoglobin data ( Mean [ SD ] age of 76.06[4.84]), the prevalence of antenatal maternal anaemia and postnatal child anaemia was 38.20% (34/89) and 47.19% (42/89), respectively. There was no association between maternal and child anaemia (c 2 = 0.799; p =0.372), and child anaemia did not contribute to regional brain volume differences associated with maternal anaemia. Conclusions Associations between maternal anaemia and regional child brain volumes previously reported at 2-3 years of age were consistent and persisted to 6-7 years of age. Findings support the importance of optimizing antenatal maternal health and reinforce these brain regions as a future research focus on intervention outcomes.

Precision Engineering of Chondrocyte Microenvironments: Investigating the Optimal Reaction Conditions for Type B Gelatin Methacrylate Hydrogel Matrix for TC28a2 Cells.

Gelatin methacrylate (GelMA) is a photocrosslinkable biomaterial that has gained widespread use in tissue engineering due to its favorable biological attributes and customizable physical and mechanical traits. While GelMA is compatible with various cell types, distinct cellular responses are observed within GelMA hydrogels. As such, tailoring hydrogels for specific applications has become imperative. Thus, our objective was to develop GelMA hydrogels tailored to enhance cell viability specifically for TC28a2 chondrocytes in a three-dimensional (3D) cell culture setting. We investigated GelMA synthesis using PBS and 0.25M CB buffer, analyzed the mechanical and physical traits of GelMA hydrogels, and evaluated how varying GelMA crosslinking conditions (GelMA concentration, photoinitiator concentration, and UV exposure time) affected the viability of TC28a2 chondrocytes. The results revealed that GelMA synthesis using 0.25M CB buffer led to a greater degree of methacrylation compared to PBS buffer, and the LAP photoinitiator demonstrated superior efficacy for GelMA gelation compared to Irgacure 2959. Additionally, the stiffness, porosity, and swelling degree of GelMA hydrogels were predominantly affected by GelMA concentration, while cell viability was impacted by all crosslinking conditions, decreasing notably with increasing GelMA concentration, photoinitiator concentration, and UV exposure time. This study facilitated the optimization of crosslinking conditions to enhance cell viability within GelMA hydrogels, a critical aspect for diverse biomedical applications.

Clinical and neuroimaging predictors of benzodiazepine response in catatonia: A machine learning approach.

Catatonia is a well characterized psychomotor syndrome combining motor, behavioural and neurovegetative signs. Benzodiazepines are the first-choice treatment, effective in 70 % of cases. Currently, the factors associated with benzodiazepine resistance remain unknown. We aimed to develop machine learning models using clinical and neuroimaging data to predict benzodiazepine response in catatonic patients. This study examined a cohort of catatonic patients who underwent standardized clinical evaluation, 3 T brain MRI, and benzodiazepine trial. Based on clinical response, patients were classified as benzodiazepine responders or non-responders. Cortical thickness and regional brain volumes were measured. Two machine learning models (linear model and gradient boosting tree model) were developed to identify predictors of treatment response using clinical, demographic, and neuroimaging data. The cohort included 65 catatonic patients, comprising 30 benzodiazepine responders and 35 non-responders. Using clinical data alone, the linear model achieved 63% precision, 51% recall, a specificity of 61%, and 58% AUC, while the gradient boosting tree (GBT) model attained 46% precision, 60% recall, a specificity of 62% and 64% AUC. Incorporating neuroimaging data improved model performance, with the linear model achieving 66% precision, 57% recall, a specificity of 67%, and 70% AUC, and the GBT model attaining 50% precision, 50% recall, a specificity of 62% and 70% AUC. The integration of imaging data with demographic and clinical information significantly enhanced the predictive performance of the models. The duration of the catatonic syndrome, along with the presence of mitgehen (passive obedience) and immobility/stupor, and the volume of the right medial orbito-frontal cortex emerged as important factors in predicting non-response to benzodiazepines.

Heat 'n Beat: A Universal High-Throughput End-to-End Proteomics Sample Processing Platform in under an Hour.

Proteomic analysis by mass spectrometry of small (≤2 mg) solid tissue samples from diverse formats requires high throughput and comprehensive proteome coverage. We developed a nearly universal, rapid, and robust protocol for sample preparation, suitable for high-throughput projects that encompass most cell or tissue types. This end-to-end workflow extends from original sample to loading the mass spectrometer and is centered on a one-tube homogenization and digestion method called Heat 'n Beat (HnB). It is applicable to most tissues, regardless of how they were fixed or embedded. Sample preparation was divided into separate challenges. The initial sample washing and final peptide cleanup steps were adapted to three tissue sources: fresh frozen (FF), optimal cutting temperature (OCT) compound embedded (FF-OCT), and formalin-fixed paraffin embedded (FFPE). Third, for core processing, tissue disruption and lysis were decreased to a 7 min heat and homogenization treatment, and reduction, alkylation, and proteolysis were optimized into a single step. The refinements produced near doubled peptide yield when compared to our earlier method ABLE delivered a consistently high digestion efficiency of 85-90%, reported by ProteinPilot, and required only 38 min for core processing in a single tube, with the total processing time being 53-63 min. The robustness of HnB was demonstrated on six organ types, a cell line, and a cancer biopsy. Its suitability for high-throughput applications was demonstrated on a set of 1171 FF-OCT human cancer biopsies, which were processed for end-to-end completion in 92 h, producing highly consistent peptide yield and quality for over 3513 MS runs.

Assessing the Readability of Online English and Spanish Language Patient Education Resources Provided by the American Society of Plastic Surgeons, American Society of Aesthetic Plastic Surgeons, and American Society of Reconstructive Microsurgeons.

INTRODUCTION: The National Institutes of Health recommends that patient education materials (PEMs) be written at the sixth grade level. However, PEMs online are still generally difficult to read. The usefulness of online PEMs depends on their comprehensibility. OBJECTIVES: This study assessed the readability of PEMs from national Plastic and Reconstructive Surgery (PRS) organization websites. METHODS: Patient education materials were collected from 3 prominent PRS organizations-the American Society of Plastic Surgeons (ASPS), American Society of Aesthetic Plastic Surgeons (ASAPS), and the American Society of Reconstructive Microsurgeons (ASRM). ASPS PEMs were organized into reconstructive and cosmetic groups, and then further subdivided into English and Spanish subgroups. ASAPS and ASRM PEMs provided cosmetic and reconstructive comparison groups to ASPS, respectively. Readability scores were generated using the Simple Measure of Gobbledygook (SMOG) and the Spanish SMOG scales. RESULTS: Overall, all PEMs failed to meet readability guidelines. Within ASPS, Spanish PEMs were easier to read than English PEMs ( P < 0.001), and cosmetic PEMs were easier to read than reconstructive PEMs ( P < 0.05). There was no significant difference between ASPS cosmetic and ASAPS PEMs ( P = 0.36), nor between ASPS reconstructive and ASRM PEMs ( P = 0.65). ASAPS and ASRM did not have any Spanish PEMs, and 92% of all ASPS PEMs were in English. CONCLUSION: Although PRS societies strive to better educate the public on the scope of PRS, PRS ranks lowly in public understanding of its role in patient care. In addition, Spanish language PEMs from the 3 PRS organizations are severely lacking. Addressing these concerns will make online patient resources more equitable for various patient populations.

Spinal fMRI demonstrates segmental organisation of functionally connected networks in the cervical spinal cord: A test-retest reliability study.

Resting functional magnetic resonance imaging (fMRI) studies have identified intrinsic spinal cord activity, which forms organised motor (ventral) and sensory (dorsal) resting-state networks. However, to facilitate the use of spinal fMRI in, for example, clinical studies, it is crucial to first assess the reliability of the method, particularly given the unique anatomical, physiological, and methodological challenges associated with acquiring the data. Here, we characterise functional connectivity relationships in the cervical cord and assess their between-session test-retest reliability in 23 young healthy volunteers. Resting-state networks were estimated in two ways (1) by estimating seed-to-voxel connectivity maps and (2) by calculating seed-to-seed correlations. Seed regions corresponded to the four grey matter horns (ventral/dorsal and left/right) of C5-C8 segmental levels. Test-retest reliability was assessed using the intraclass correlation coefficient. Spatial overlap of clusters derived from seed-to-voxel analysis between sessions was examined using Dice coefficients. Following seed-to-voxel analysis, we observed distinct unilateral dorsal and ventral organisation of cervical spinal resting-state networks that was largely confined in the rostro-caudal extent to each spinal segmental level, with more sparse connections observed between segments. Additionally, strongest correlations were observed between within-segment ipsilateral dorsal-ventral connections, followed by within-segment dorso-dorsal and ventro-ventral connections. Test-retest reliability of these networks was mixed. Reliability was poor when assessed on a voxelwise level, with more promising indications of reliability when examining the average signal within clusters. Reliability of correlation strength between seeds was highly variable, with the highest reliability achieved in ipsilateral dorsal-ventral and dorso-dorsal/ventro-ventral connectivity. However, the spatial overlap of networks between sessions was excellent. We demonstrate that while test-retest reliability of cervical spinal resting-state networks is mixed, their spatial extent is similar across sessions, suggesting that these networks are characterised by a consistent spatial representation over time.

High Prevalence of New Clinically Significant Findings in Patients With Embolic Stroke of Unknown Source Evaluated by Cardiac Magnetic Resonance Imaging.

BACKGROUND: Embolic stroke of unknown source (ESUS) accounts for 1 in 6 ischemic strokes. Current guidelines do not recommend routine cardiac magnetic resonance (CMR) imaging in ESUS, and beyond the identification of cardioembolic sources, there are no data assessing new clinical findings from CMR in ESUS. This study aimed to assess the prevalence of new cardiac and noncardiac findings and to determine their impact on clinical care in patients with ESUS. METHODS AND RESULTS: In this prospective, multicenter, observational study, CMR imaging was performed within 3 months of ESUS. All scans were reported according to standard clinical practice. A new clinical finding was defined as one not previously identified through prior clinical evaluation. A clinically significant finding was defined as one resulting in further investigation, follow-up, or treatment. A change in patient care was defined as initiation of medical, interventional, surgical, or palliative care. From 102 patients recruited, 96 underwent CMR imaging. One or more new clinical findings were observed in 59 patients (61%). New findings were clinically significant in 48 (81%) of these patients. Of 40 patients with a new clinically significant cardiac finding, 21 (53%) experienced a change in care (medical therapy, n=15; interventional/surgical procedure, n=6). In 12 patients with a new clinically significant extracardiac finding, 6 (50%) experienced a change in care (medical therapy, n=4; palliative care, n=2). CONCLUSIONS: CMR imaging identifies new clinically significant cardiac and noncardiac findings in half of patients with recent ESUS. Advanced cardiovascular screening should be considered in patients with ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04555538.

ECG Feature Importance Rankings: Cardiologists vs. Algorithms.

Feature importance methods promise to provide a ranking of features according to importance for a given classification task. A wide range of methods exist but their rankings often disagree and they are inherently difficult to evaluate due to a lack of ground truth beyond synthetic datasets. In this work, we put feature importance methods to the test on real-world data in the domain of cardiology, where we try to distinguish three specific pathologies from healthy subjects based on ECG features comparing to features used in cardiologists' decision rules as ground truth. We found that the SHAP and LIME methods and Chi-squared test all worked well together with the native Random forest and Logistic regression feature rankings. Some methods gave inconsistent results, which included the Maximum Relevance Minimum Redundancy and Neighbourhood Component Analysis methods. The permutation-based methods generally performed quite poorly. A surprising result was found in the case of left bundle branch block, where T-wave morphology features were consistently identified as being important for diagnosis, but are not used by clinicians.

Magnetic resonance imaging for diagnostic workup of embolic stroke of undetermined source: A systematic review.

BACKGROUND: Embolic stroke of undetermined source (ESUS) refers to ischemic stroke where the underlying cause of thromboembolism cannot be found despite the recommended diagnostic workup. Unidentified source of emboli hinders clinical decision-making and patient management with detrimental consequences on long-term prognosis. The rapid development and versatility of magnetic resonance imaging (MRI) make it an appealing addition to the diagnostic routine of patients with ESUS for the assessment of potential vascular and cardiac embolic sources. AIMS: To review the use of MRI in the identification of cardiac and vascular embolic sources in ESUS and to assess the reclassification value of MRI examinations added to the conventional workup of ESUS. SUMMARY OF REVIEW: We reviewed the use of cardiac and vascular MRI for the identification of a variety of embolic sources associated with ESUS, including atrial cardiomyopathy, left ventricular pathologies, and supracervical atherosclerosis in carotid and intracranial arteries and in distal thoracic aorta. The additional reclassification after MRI examinations added to the workup of patients with ESUS ranged from 6.1% to 82.3% and varied depending on the combination of imaging modalities. CONCLUSION: MRI techniques allow us to identify additional cardiac and vascular embolic sources and may further decrease the prevalence of patients with the diagnosis of ESUS.

Reliability of quantitative sensory testing in the assessment of somatosensory function after high-frequency stimulation-induced sensitisation of central nociceptive pathways.

ABSTRACT: The high frequency stimulation (HFS) model can be used alongside quantitative sensory testing (QST) to assess the sensitisation of central nociceptive pathways. However, the validity and between-session reliability of using QST z -score profiles to measure changes in mechanical and thermal afferent pathways in the HFS model are poorly understood. In this study, 32 healthy participants underwent QST before and after HFS (5× 100 Hz trains; 10× electrical detection threshold) in the same heterotopic skin area across 2 repeated sessions. The only mechanical QST z -score profiles that demonstrated a consistent gain of function across repeated test sessions were mechanical pain threshold (MPT) and mechanical pain sensitivity (MPS), which were associated with moderate and good reliability, respectively. There was no relationship between HFS intensity and MPT and MPS z -score profiles. There was no change in low intensity, but a consistent facilitation of high-intensity pin prick stimuli in the mechanical stimulus response function across repeated test sessions. There was no change in cold pain threshold (CPT) and heat pain threshold (HPT) z -score profiles across session 1 and 2, which were associated with moderate and good reliability, respectively. There were inconsistent changes in the sensitivity to innocuous thermal QST parameters, with cool detection threshold (CDT), warm detection threshold (WDT), and thermal sensory limen (TSL) all producing poor reliability. These data suggest that HFS-induced changes in MPS z -score profiles is a reliable way to assess experimentally induced central sensitisation and associated secondary mechanical hyperalgesia in healthy participants.

Optimized strategy for real-time qPCR detection of Onchocerca volvulus DNA in pooled Simulium sp. blackfly vectors.

BACKGROUND: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, with at least two African countries having now stopped MDA as they approach verification of elimination. It is essential that accurate data for active transmission are used to assist in making the critical decision to stop MDA, since missing low levels of transmission and infection can lead to continued spread or recrudescence of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Current World Health Organization guidelines for MDA stopping decisions and post-treatment surveillance include screening pools of the Simulium blackfly vector for the presence of O. volvulus larvae using a PCR-ELISA-based molecular technique. In this study, we address the potential of an updated, practical, standardized molecular diagnostic tool with increased sensitivity and species-specificity by comparing several candidate qPCR assays. When paired with heat-stable reagents, a qPCR assay with a mitochondrial DNA target (OvND5) was found to be more sensitive and species-specific than an O150 qPCR, which targets a non-protein coding repetitive DNA sequence. The OvND5 assay detected 19/20 pools of 100 blackfly heads spiked with a single L3, compared to 16/20 for the O150 qPCR assay. CONCLUSIONS/SIGNIFICANCE: Given the improved sensitivity, species-specificity and resistance to PCR inhibitors, we identified OvND5 as the optimal target for field sample detection. All reagents for this assay can be shipped at room temperature with no loss of activity. The qPCR protocol we propose is also simpler, faster, and more cost-effective than the current end-point molecular assays.

An expert-novice comparison of lifeguard specific vigilance performance.

INTRODUCTION: Lifeguards must maintain alertness and monitor an aquatic space across extended periods. However, lifeguard research has yet to investigate a lifeguard's ability to maintain performance over time and whether this is influenced by years of certified experience or the detection difficulty of a drowning incident. The aim of this study was to examine whether lifeguard experience, drowning duration, bather number, and time on task influences drowning detection performance. METHOD: A total of 30 participants took part in nine 60-minute lifeguard specific tasks that included 11 drowning events occurring at five-minute intervals. Each task had manipulated conditions that acted as the independent variables, including bather number and drowning duration. RESULTS: The experienced group detected a greater number of drowning events per task, compared to novice and naïve groups. Findings further highlighted that time, bather number, and drowning duration has a substantial influence on lifeguard specific drowning detection performance. PRACTICAL APPLICATIONS: It is hoped that the outcome of the study will have applied application in highlighting the critical need for lifeguard organizations to be aware of a lifeguard's capacity to sustain attention, and for researchers to explore methods for minimizing any decrement in vigilance performance.

Development of neonatal-specific sequences for portable ultralow field magnetic resonance brain imaging: a prospective, single-centre, cohort study.

Background: Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies. Methods: Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested. Findings: Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40+2 weeks (range: 31+3-53+4). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle. Interpretation: On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted. Funding: The Bill and Melinda Gates Foundation, the MRC, the Wellcome/EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas' and South London & Maudsley NHS Foundation Trusts and King's College London.

AF and in-hospital mortality in COVID-19 patients.

Background: There are conflicting data on whether new-onset atrial fibrillation (AF) is independently associated with poor outcomes in COVID-19 patients. This study represents the largest dataset curated by manual chart review comparing clinical outcomes between patients with sinus rhythm, pre-existing AF, and new-onset AF. Objective: The primary aim of this study was to assess patient outcomes in COVID-19 patients with sinus rhythm, pre-existing AF, and new-onset AF. The secondary aim was to evaluate predictors of new-onset AF in patients with COVID-19 infection. Methods: This was a single-center retrospective study of patients with a confirmed diagnosis of COVID-19 admitted between March and September 2020. Patient demographic data, medical history, and clinical outcome data were manually collected. Adjusted comparisons were performed following propensity score matching between those with pre-existing or new-onset AF and those without AF. Results: The study population comprised of 1241 patients. A total of 94 (7.6%) patients had pre-existing AF and 42 (3.4%) patients developed new-onset AF. New-onset AF was associated with increased in-hospital mortality before (odds ratio [OR] 3.58, 95% confidence interval [CI] 1.78-7.06, P < .005) and after (OR 2.80, 95% CI 1.01-7.77, P < .005) propensity score matching compared with the no-AF group. However, pre-existing AF was not independently associated with in-hospital mortality compared with patients with no AF (postmatching OR: 1.13, 95% CI 0.57-2.21, P = .732). Conclusion: New-onset AF, but not pre-existing AF, was independently associated with elevated mortality in patients hospitalised with COVID-19. This observation highlights the need for careful monitoring of COVID-19 patients with new-onset AF. Further research is needed to explain the mechanistic relationship between new-onset AF and clinical outcomes in COVID-19 patients.

A Multi-method Exploratory Evaluation of a Service Designed to Improve Medication Safety for Patients with Monitored Dosage Systems Following Hospital Discharge.

BACKGROUND AND OBJECTIVE: Medication safety problems are common post-hospital discharge, and an important global healthcare improvement target. The Transfers of Care Around Medicines (TCAM) service was launched by a National Health Service Trust in the North-West of England, initially focusing on patients with new or existing Monitored Dosage Systems (MDS). The TCAM service is designed to enable the prompt transfer of medication information, with referrals made by hospitals at discharge to a named community pharmacy. This study aimed to explore the utilisation and impact of the TCAM service on medication safety. METHODS: The evaluation included a descriptive analysis of 3033 anonymised patient referrals to 71 community pharmacies over a 1-year period alongside an assessment of the impact of the TCAM service on unintentional medication discrepancies and adverse drug events using a retrospective before-and-after study design. Impact data were collected across 18 general practices by 16 trained clinical pharmacists. RESULTS: Most patient referrals (70%, 2126/3033) were marked as 'completed' by community pharmacies, with 15% of completed referrals delayed beyond 30 days. Screening of 411 patient records by clinical pharmacists yielded no statistically significant difference in unintentional medication discrepancies or adverse drug event rates following TCAM implementation using a multivariable regression analysis (unintentional medication discrepancies adjusted odds ratio = 0.79 [95% confidence interval 0.44-1.44, p = 0.46]; and adverse drug events adjusted odds ratio = 1.19 [95% confidence interval 0.57-2.45, p = 0.63]), although there remained considerable uncertainty. CONCLUSIONS: The TCAM service facilitated a number of community pharmacy services offered to patients with monitored dosage systems; but the impact of the intervention on unintentional medication discrepancies and adverse drug event rates post-hospital discharge for this patient group was uncertain. The results of this exploratory study can inform the ongoing implementation of the TCAM service at hospital discharge and highlight the need to understand service implementation in different contexts, which may influence its impact on medication safety.

MedalCare-XL: 16,900 healthy and pathological synthetic 12 lead ECGs from electrophysiological simulations.

Mechanistic cardiac electrophysiology models allow for personalized simulations of the electrical activity in the heart and the ensuing electrocardiogram (ECG) on the body surface. As such, synthetic signals possess known ground truth labels of the underlying disease and can be employed for validation of machine learning ECG analysis tools in addition to clinical signals. Recently, synthetic ECGs were used to enrich sparse clinical data or even replace them completely during training leading to improved performance on real-world clinical test data. We thus generated a novel synthetic database comprising a total of 16,900 12 lead ECGs based on electrophysiological simulations equally distributed into healthy control and 7 pathology classes. The pathological case of myocardial infraction had 6 sub-classes. A comparison of extracted features between the virtual cohort and a publicly available clinical ECG database demonstrated that the synthetic signals represent clinical ECGs for healthy and pathological subpopulations with high fidelity. The ECG database is split into training, validation, and test folds for development and objective assessment of novel machine learning algorithms.

Self-Assembly of Uniaxial Fullerene Supramolecules Aligned within Carbon Nanotube Fibers.

The conductivity and strength of carbon nanotube (CNT) wires currently rival those of existing engineering materials; fullerene-based materials have not progressed similarly, despite their exciting transport properties such as superconductivity. This communication reveals a new mechanically robust wire of mutually aligned fullerene supramolecules self-assembled between CNT bundles, where the fullerene supramolecular internal crystal structure and outer surface are aligned and dispersed with the CNT bundles. The crystallinity, crystal dimensions, and other structural features of the fullerene supramolecular network are impacted by a number of important production processes such as fullerene concentration and postprocess annealing. The crystal spacing of the CNTs and fullerenes is not altered, suggesting that they are not exerting significant internal pressure on each other. In low concentrations, the addition of networked fullerenes makes the CNT wire mechanically stronger. More importantly, novel mutually aligned and networked fullerene supramolecules are now in a bulk self-supporting architecture.

Molecular-enriched functional connectivity in the human brain using multiband multi-echo simultaneous ASL/BOLD fMRI.

Receptor-enriched analysis of functional connectivity by targets (REACT) is a strategy to enrich functional MRI (fMRI) data with molecular information on the neurotransmitter distribution density in the human brain, providing a biological basis to the functional connectivity (FC) analysis. Although this approach has been used in BOLD fMRI studies only so far, extending its use to ASL imaging would provide many advantages, including the more direct link of ASL with neuronal activity compared to BOLD and its suitability for pharmacological MRI studies assessing drug effects on baseline brain function. Here, we applied REACT to simultaneous ASL/BOLD resting-state fMRI data of 29 healthy subjects and estimated the ASL and BOLD FC maps related to six molecular systems. We then compared the ASL and BOLD FC maps in terms of spatial similarity, and evaluated and compared the test-retest reproducibility of each modality. We found robust spatial patterns of molecular-enriched FC for both modalities, moderate similarity between BOLD and ASL FC maps and comparable reproducibility for all but one molecular-enriched functional networks. Our findings showed that ASL is as informative as BOLD in detecting functional circuits associated with specific molecular pathways, and that the two modalities may provide complementary information related to these circuits.