A document by Junyi Gong. Click on the document to view its contents.

This Perspective argues that the NHS in the UK is facing a critical ‘tipping point’ which means that its very survival is at stake. The article considers the political responses to this crisis - (briefly) from the Conservative government; (briefly) from the ‘anti-NHS’ Right in politics; (briefly) from the ‘centre’ in politics in the form of the Tony Blair Institute for Global Change; and (in depth) from the left-of-centre, the Labour Party. Labour is likely to form the next government, which is why its approach (in terms of both political strategy and the substance of health policy) is considered in depth. It is argued that Labour’s approach, derived from an understandable desire by leader Sir Keir Starmer to disown its ‘unelectable’ recent past, is currently inadequate for the task of putting the NHS on a secure footing for the future.

This paper presents the development and implementation of a multi-UAV system focused on coverage path planning on multiple separated areas capable of re-planning the collective mission in case of unexpected events. For this purpose, we present a distributed-centralized architecture that uses heuristic and computationally efficient methods to perform the planning/re-planning and decision-making tasks during the control of the mission execution. We performed a computational evaluation of the algorithms, comparing them with other proposals, together with experiments in simulated and real flights. The results show that the system can distribute tasks equitably among the aircraft in an efficient way, even in the middle of the flight, when facing unexpected events; and show a higher computational efficiency when compared to multiple proposals in the state of the art.

A document by Harkesh Arora. Click on the document to view its contents.

Introduction: Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease in adults, has excellent long-term survival. However, many patients (30-45%) develop late arrhythmias. Previous studies have identified predictors of arrhythmia (atrial or ventricular) using clinical markers that predate arrhythmia onset for many years. Our objective was to develop predictive models for incident atrial arrhythmias or any arrhythmia (atrial and ventricular) within two years of clinical evaluation and diagnostic testing. Methods: A single-center retrospective cohort study of 188 adults with repaired TOF. We included only patients with results from ECG and echocardiogram data in the required time interval (3-24 months before first arrhythmia for cases; 24 months of follow-up for controls). Predictive multivariable models for risk of atrial arrhythmia using logistic regression with a least absolute shrinkage and selection operator (LASSO) penalty were developed. Results: Of 41 demographic, surgical, and diagnostic variables, six were selected as having predictive value for atrial arrhythmia based on cross validation. The factors with the greatest predictive value in decreasing order were moderate / severe tricuspid regurgitation (adjusted odds ratio (OR) 149.42), QRS fragmentation (OR 28.08), severe pulmonary regurgitation (OR 8.22), RV systolic dysfunction (OR 2.95), 1 st degree AV block, and age at time of surgical repair. Conclusion: Predictors for atrial or any arrhythmia in our study were similar, suggesting a common pathophysiologic substrate, i.e., abnormal right ventricle anatomical function and electrophysiologic properties (conduction and repolarization).

Per- and polyfluoroalkyl substances (PFASs) have become a significant concern in recent years as a new type of pollutant due to their ability to accumulate and magnify in the environment and living organisms. When PFASs enter the environment, they can have adverse health effects on humans. Therefore, it is important to monitor and detect PFASs. The current method for detecting PFASs involves using expensive equipment and complex procedures, such as chromatography and mass spectrometry. However, new methods that are simpler and more cost-effective, such as optical and electrochemical techniques, have been developed and applied. These methods have the potential to detect PFASs quickly in real-time, make detection devices smaller, and reduce analysis time. In this review, we summarize recent advancements in PFAS detection sensors. We categorize and explain the principles and mechanisms of these sensors, and compare their limits of detection and sensitivity. Finally, we discuss the future challenges and improvements needed for PFAS sensors, including commercialization and other issues.

In the last few years novel ablative technologies featuring several devices incorporating different energy sources and catheter design for ensuring an effective PVI have been proposed. In particular, two prominent technologies, such as the non-thermal ablation modality based on pulsed field ablation (also defined as “electroporation”) and radio frequency balloon-based catheter has been introduced in the clinical practice. The adoption of such technologies aims at simplifying PVI procedures, improving efficacy, and increasing safety. Furthermore, the evaluation of the extension of area of lesion promoted by the two technologies might affect the clinical outcome

AIM Levetiracetam is a widely used anti-epileptic in the critical care setting that is almost exclusively (>90%) renally excreted. A significant number of critically unwell patients develop renal failure requiring haemofiltration. This paper investigates the pharmacokinetics of levetiracetam in such patients and the implications on dosing strategies. METHODS A systematic review of the available literature from 2000 was conducted. 7 articles were identified for inclusion from 54 records. A novel hybrid model was used to evaluate the quality of pharmacokinetic and haemofiltration data. Simulations were performed using pooled pharmacokinetic data to evaluate various dosing strategies. RESULTS Total clearance was 3.49 – 4.63L/hr (mean 3.55, S.D. 0.52). Elimination half-life was 5.66 – 12.88 hours (mean 9.41, S.D. 2.86). Volume of distribution was 0.45 – 0.73 L/kg. Levetiracetam clearance from CRRT was 52 – 73% (mean 54.7%, S.D. 13.5). At 72 hours, a significant proportion of simulated patients who received the recommended dose of levetiracetam demonstrated sub-therapeutic drug concentrations. Conversely, the majority who received a standard loading dose (60mg/kg) and twice daily doses in excess of 750mg demonstrated more consistent therapeutic drug concentrations. CONCLUSION Levetiracetam clearance in haemofiltration is similar to healthy adults with normal renal function. The current recommendation to dose as in CKD Stage 3b is likely to result in sub-therapeutic drug concentrations in a high number of patients. A twice daily dosing of 500 – 1,000 mg with an initial loading dose of 60mg/kg should be considered in such patients alongside therapeutic drug monitoring.

The development of an integrated technology of solar energy building materials; a flat-plate solar collector was designed and manufactured. The absorption plates and the outer frames of the solar collector are made of corrosion-resistant aluminum alloy. The solar collector has a thinner cross-sectional structure, small mass, functional integrity, and rigidity. Thus, it is convenient for the installation, removal, maintenance, and replacement of the collectors. We have used excellent composite coating materials to absorb the higher solar energies and increase the absorption rate of the solar panels. From the test results, the emissivity of the solar energy absorption film of the collector core plate was very high; the average thermal collector efficiency of building material-integrated collectors still reaches more than 50%. We conducted the experimental results that the solar collector materials for construction have higher thermal efficiency than the collector installed on the platform. In future improvements, the glass panels should be changed to 3mm thickness to reduce weight and increase shortwave transmission. The absorbing film also needs to be improved to improve the thermal efficiency of the solar panel. This paper mainly introduces the collector design and thermal performance.

Objectives: Right ventricle (RV) dysfunction has a significant impact on the morbidity and mortality of critically ill patients and is associated with worse outcomes. This study aims to analyze the frequency of echocardiographic alterations of the RV in children undergoing invasive mechanical ventilation (IMV). Methods: Observational study conducted on patients undergoing mechanical ventilation in a pediatric intensive care unit from May 2019 to June 2022. Bedside echocardiograms were performed, and measurements of tricuspid annular plane systolic excursion (TAPSE), tissue Doppler S’ wave, and right ventricle/left ventricle (RV/LV) ratio were evaluated. Results: A total of 146 echocardiograms were analyzed, with a median age of 7 months, 64.4% were infants, and 51.4% were female. It was observed that 24% (35) had TAPSE alterations, 14% (20) had alterations in the S’ wave, and 10.7% (15) had RV/LV ratio altered. Considering RV dysfunction as any of these altered parameters, the frequency was 38.5% (55), with cardiac index weakly correlated with TAPSE (r=0.171; p<0.048) and S’ wave (r=0.281; p<0.001). There was no significant association between echocardiographic alterations and respiratory parameters. Regarding hemodynamic status, the median Vasoactive-inotropic Score was higher in the dysfunction group (7.5 vs. 3; p<0.048), as well as lactate levels (1.74 vs. 1.3; p<0.015). None of the variables were associated with mortality, duration of IMV or length of hospital stay. Conclusions: Echocardiographic alterations of the RV are frequent in children undergoing MV. Echocardiography is a non-invasive tool that aids in identifying this condition, which can impact the management of critically ill patients.

Humans obtain information from various kinds of stimuli. The perception of these external stimuli may be modulated by the ongoing pre-stimulus brain activities. Multiple cognitive functions including arousal, attention (spatial and feature-based) and mental imagery may start prior to stimulus onset. Different roles of pre-stimulus oscillations in these cognitive functions, including gating by inhibition via pre-stimulus alpha signals, noise clearance, large-scale brain synchronizations, and motor preparation are discussed. We will also describe the effect of pre-stimulus explicit and implicit expectation on later processing and the way it is coupled with pre-stimulus attention. Finally, we will explain the temporal organization of pre-stimulus oscillations and their modulatory effect on the perception of the incoming stimulus. We will present current evidence concerning these different cognitive connotations and discuss present controversies.

Objective: To evaluate the implementation of the London Measure of Unplanned Pregnancy (LMUP) in antenatal care. Design: Mixed methods evaluation of a pilot. Setting: Antenatal care at University College London Hospital and Homerton Hospital, England, 2019-2022. Population: Pregnant women attending antenatal care at one of the sites during the evaluation. Methods: Quantitative and psychometric analysis of anonymous data and qualitative analysis of interviews and focus groups with women and midwives, using a Framework Analysis. Main Outcome Measures: Acceptability of the inclusion of the LMUP, measured by completion rates and women’s and midwives opinions. Results: Completion of the LMUP at UCLH stabilised at around 70% and the LMUP performed as expected. Asking the LMUP at antenatal booking appointments is feasible and acceptable to women and midwives. Advantages of asking the LMUP, highlighted by participants, include providing additional support and personalising care. Midwives’ concerns about judgment were unsubstantiated; women with unplanned pregnancies valued such discussions. Conclusions: These findings support the implementation of the LMUP in routine antenatal care and show how it can provide valuable insights into the circumstances of women’s pregnancies. This can be used to help midwives personalise care, and potentially reduce adverse outcomes and subsequent unplanned pregnancy. Integration of the LMUP into the Maternity Services Data Set, will establish national data collection for a population-level measure of unplanned pregnancy, serving as a key outcome measure for sexual and reproductive health and enabling analysis of the prevalence, factors, and implications of unplanned pregnancies across subpopulations to inform implementation. Funding : NIHR PDF-2017-10-021

The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5’→3’ exoribonuclease paralogues that are very similar. In yeast, they are called Xrn1, which shuttles between the nucleus and cytoplasm and executes major cytoplasmic mRNA decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes in the nucleus. Xrn1 is 40% homologous to Rat1 but has an extra ~500 amino acids C-terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes “co-translational mRNA decay”. The division of labor between the two enzymes is still enigmatic and can serve as a paradigm for division of labor of many other paralogues. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the actual segregation of the two paralogues plays roles in their specific functions. However, segregation is not sufficient for fully complementing Xrn1 function. Specifically, cRat1 can only partially recover cell volume, mRNA stability, proliferation rate, 5’→3’ decay alterations that characterize xrn1Δ cells. In particular, co-translational decay is only little complemented by cRat1. Adding the Xrn1 C-terminal domain to Rat1 does not improve the phenotypes indicating that lack of C-terminal is not the reason for the partial complementation. Collectively, it seems that during evolution the two paralogues acquire unique features that make the division of work beneficial.

This paper proposes an online scheme of WADC for damping inter-area oscillations based on the intelligent CART technique and optimal combinations of SGs. In real-time environment, by using the SGs oscillatory signals though COI frame, GISs (ΔωCOI and ΔδCOI) are provided. By using GISs as input through two CARTs, two individual controlling gains K1 and K2 are estimated which used through GCSs for online representations to SGs excitation systems. In this case, considering an online two-step process based on the pade approximation theory, the unavoidable time latencies through GIS and GCS signals are compensated. Also, for estimating proper SGs with high damping performances, a CI is proposed which by online evaluations of the SGs output electric powers and the Thevenin impedances and solving CI by the BGA, proper SGs are identified. In this case, by evaluating PMU phasors through three proposed circle equations, the SGs Thevenin impedances are estimated online. The effectiveness of the proposed comprehensive WADC scheme is examined on the IEEE-39 bus system with indicating positive effects through damping the inter-area oscillation.

The notion of racism as a dichotomy in white people in the United States is being challenged; racism exists along a spectrum with covert manifestations. Understanding how well-meaning white people (WMWP) can harbor unexamined racial biases and contribute to systemic racism is crucial. Using survey data from a nationally representative sample of white people (n=239), we explored differences between participants on cognitive, affective, and behavioral racial attitudes, as well as support for punitive drug policies, which have historically harmed Black communities. We found cognitive and affective differences among white people subgroups, including that WMWP report high racial resentment and low support for antiracism, despite their expressed motivation to be nonprejudiced toward Black people. We also found that WMWP are likely to support punitive drug policies, indicating a misalignment between their intentions to treat Black people in egalitarian ways, and the negative impact their actions can have on Black communities. This might be due to their resistance to changing the societal status quo. Addressing systemic racism requires both bottom-up changes in individual attitudes and top-down changes in public policies. By shedding light on these associations, this study provides valuable insights for efforts towards reducing racism and promoting racial equality.

Considering difficulties of achieving vertical incidence of beam in different positions of skin, it’s significant to study potential effects of incidence angles of laser on incisions. Surgical platform with a 1064nm continuous fiber laser was established. Incident angle was adopted and real-time temperature fluctuations in laser operating area could be monitored. The rats were treated with laser at day 0 and day 3 after incision modeling, and H&E, Masson, Sirius Red and Immuno-histochemical staining and enzyme-linked immunosorbent assay were adopted at day 3,7,14 to analyze the performance of healing. Laser with energy density of 67.54J/mm 2 can effectively accelerate wound healing in vivo, in which laser with incident angle around 60° can effectively avoid scar hyperplasia. Therefore, the use of low energy laser with small deflection angle has a good clinical application prospect in promoting wound healing.

Cancer remains one of the most complex and challenging diseases in mankind. To address the need for a personalized treatment approach for particularly complex tumor cases, molecular tumor boards (MTBs) have been initiated. MTBs are interdisciplinary teams that perform in-depth molecular diagnostics to cooperatively and interdisciplinarily advise on the best therapeutic strategy. Current routine molecular diagnostics are routinely performed on the transcriptomic and genomic levels, aiming for the identification of tumor-driving mutations. However, these approaches can only partially capture the actual phenotype as well as the molecular key players of tumor growth and progression. Thus, direct investigation of the expressed proteins and activated signaling pathways provide complementary information on the tumor-driving molecular characteristics of the tissue. Technological advancements in mass-spectrometry-based proteomics enable the robust, rapid, and sensitive detection of thousands of proteins in minimal sample amounts, paving the way for clinical proteomics and the probing of oncogenic signaling activity. Therefore, proteomics is currently being integrated into molecular diagnostics within MTBs and holds promising potential in aiding tumor classification and identifying personalized treatment strategies. This review gives an introduction to MTBs and describes current state-of-the-art clinical proteomics, its potential in precision oncology, and highlights the benefits of multi-omic data integration.

Intuitive Eating Scale-2 (IES-2) is a measurement of intuitive eating behaviors and has been validated, with traditional latent variable approaches, in youth and adults from a number of different populations, including college students in China. However, there still lacks the evaluation of the psychometric properties of the IES-2 in adults from the Chinese general population. Moreover, psychometric network analysis, as a complement to traditional latent variable approaches, has not been used for examining the psychometric properties of the IES-2. Thus, the present study aimed to use a psychometric network approach to evaluate the psychometric properties of the IES-2 in Chinese adults from the general population. A sample of 700 Chinese general adults (50% women; M age = 31.13 years, SD = 9.19) were included in the present study. Psychometric network analysis was performed by using EGAnet and psychonetrics packages on R 4.2.0. Exploratory graph analysis (EGA) identified four dimensions, which were well-separated in the estimated network. The network structure showed excellent stability and metric measurement invariance (i.e., network loadings) across men and women. Furthermore, several items in the IES-2 were identified as key nodes in the network of the IES-2 that may be important for the developement and maintenance of intuitive eating. For example, two items related to reliance on body cues were the most impactful nodes in the complete network. The findings of our study provide further understandings of the IES-2 from the perspective of network analysis and have implications for related applications of intuitive eating interventions for general populations.

Developmental plasticity is critical for plants to adapt to constantly changing environments. Plant trichomes and root hairs are specialized epidermal cells that paly crucial roles in defense against environmental stressors. Here, we report the isolation of an Arabidopsis mutant, a berrantly b ranched t richome 6-1 ( abt6-1), with both impaired trichomes and root hairs. Map-based cloning and allelic analyses confirmed that abt6-1 is a new mutant allele of SPIRRIG ( SPI), which encodes a beige and Chediak Higashi (BEACH) domain-containing protein. SPI has been reported to facilitate actin dependent root hair development by temporally and spatially regulating the expression of BRICK1 (BRK1), a subunit of the WAVE/SCAR actin nucleating promoting complex. Based on molecular and biochemical analyses, we found BRK1 is unstable and SPI mediates BRK1 stability. Functional loss of SPI results in the accumulation of steady-state of BRK1. Moreover, we found spi mutant root hairs are hypersensitive to salt stress and their initiation and elongation were entirely inhibited under NaCl treatment. Detailed examination of the actin cytoskeleton revealed that salt stress induces an altered actin organization in root hair and root epidermal cells that resemble those in the spi mutant, implying SPI may respond to salt stress by modulating actin cytoskeleton organization.

A document by Abigail S L Lewis. Click on the document to view its contents.

Background and Purpose: GRIN-related disorders are neurodevelopmental disorders caused by mutations in the N-methyl-D-aspartate receptor (NMDAR) subunit receptor GRIN genes. A large fraction of these mutations leads to gain of function (GoF) of the NMDAR. Patients present with a combination of symptoms that includes epilepsy, intellectual disability, behavioural and motor symptoms. Controlling seizures is a significant medical need in most patients with GRIN-related disorders. The aim of this study was to assess the therapeutic efficacy of radiprodil, a selective negative allosteric modulator of GluN2B-containing NMDARs, in counteracting audiogenic seizures (AGS) in a murine model carrying the GluN2A(N615S) mutation in homozygosity (Grin2aS/S mice). Experimental Approach: Grin2aS/S mice were acutely treated with radiprodil at different doses before the presentation of a high-frequency acoustic stimulus commonly used for AGS induction. Key Results: Radiprodil significantly and dose-dependently reduced the onset and severity of AGS in Grin2aS/S mice. Conclusion and Implications: Our data clearly indicates that radiprodil has the potential to control seizures in patients with GRIN2A GoF mutations, targeting the underlying pathophysiology of the disorder.

Habitat fragmentation can increase the chance of population bottlenecks and inbreeding, and may ultimately lead to reduced fitness and local extinction. Notelaea lloydii is a native olive species endemic to Australia and listed as vulnerable due to its restricted distribution. A recent molecular systematics study has revealed there might be some geographic structuring among the N. lloydii populations. Therefore, we undertook a genome wide Single Nucleotide Polymorphism (SNP) analysis to determine levels and patterns of genetic diversity, inbreeding and gene flow within and among N. lloydii populations in south-eastern Queensland (SE-QLD). Furthermore, as the reproductive phase of a plant’s life history has a profound influence on genetic diversity, life history reproductive traits were also studied. Our SNP analysis revealed low genetic diversity, inbreeding and significant genetic structuring even among proximate populations. Results of a flower and fruit bagging experiment in two consecutive seasons revealed that N. lloydii produced many flowers but only a few fruits survived to maturity. There were no differences in bagged and un-bagged flowering and fruiting rates and therefore, we conclude that the high fruit abortion rate was probably due to inbreeding depression and/or suboptimal conditions, rather than pollinator availability and insect attack. Overall, results of this study indicate that the populations of N. lloydii are small, inbred and genetically isolated and represent unique management units that require local conservation management due to ongoing threats associated with urbanisation.

Rare Association of Plasmodium Vivax Malaria with Pulmonary Thromboembolism: A Case Report Gashaw Solela1 Merga Daba2 Zerubabel Getahun2 Yared Getachew2 Dejene Girma31Department of Internal Medicine, Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia2Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia3Department of Internal Medicine, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia

Soil erosion causes fluctuations in potato ( Solanum tuberosum L) yield, deteriorates soil health, lowers profit margins for growers, and creates adverse environmental impacts. This study focuses on developing a decision support system to improve soil health, increase profitability for growers, and lower environmental risks. Two fields are selected for this research in Prince Edward Island, Canada, during 2020-2021. Thermal and topography surveys are conducted to delineate fertility-based management zones (MZs) for soil sampling of organic matter, potato yield, and sensor data collection. Soil temperature are calibrated and validated before the growing season using handheld gun and drone-based thermal imagery. Data analysis from drone imagery reflects the coincided patterns of thermal and multispectral imagery with crop yield, topographical features, and soil water and topography (SWAT) maps. Higher temperature zones lead to excessive soil erosion that reduces soil surface nutrients, lower NDVI values, and show visual variation in bare soil imagery. Moreover, it is found that low thermal zones produce higher yields as compared to the high thermal zones. As such, the slope has a direct impact on the retention of soil moisture content; the low productivity zones retain the least soil moisture content (13.5%), followed by medium (16.1%) and high productivity zones (18.4%). This proposed decision support system can be a useful tool for mapping soil erosion and crop profitability. The data generated from these tools can be a crucial input for improved quantification of sediment transport in watershed scale models.