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Sex differences in dilated cardiomyopathy: evidence gaps and future directions
No full textDilated cardiomyopathy (DCM), which affects 1 in 250 people, is a leading global cause of heart failure and the most common indication for heart transplantation. Evidence suggests that DCM is more prevalent in men, but whether this reflects biological differences or underdiagnosis in women remains uncertain. This review explores the impact of sex on DCM, examining differences in epidemiology, etiology, clinical presentation, treatment response, and outcomes. Women often present with less severe cardiac phenotypes, including lower levels of fibrosis and better left ventricular function, yet the long-term prognosis of DCM in women is less clear. Through a systematic review and meta-analysis, we found that male DCM patients with variants in PLN, DSP, and LMNA had higher arrhythmic event rates compared with TTNtv and BAG3 carriers. In female patients with DCM, those with RBM20, DSP, and PLN variants faced the highest arrhythmic risk, and TTNtv carriers the lowest. PLN and LMNA variants had the highest heart failure risk in both sexes, whereas BAG3, RBM20, and TTN variants had lower heart failure rates in female compared with male carriers. These findings highlight the influence of sex and genotype on clinical outcomes. Current risk-stratification tools, such as those used for implantable cardioverter-defibrillators, may undertreat women owing to reliance on sex-neutral thresholds. We highlight the role of genetic, environmental, and reproductive factors in shaping these disparities, including the influence of pregnancy, pregnancy complications, and menopause. This review identifies key gaps in knowledge and calls for expanded representation of women in DCM studies and the development of sex-specific risk models. Addressing these gaps is essential to improving outcomes and advancing equitable personalized care for all DCM patients
Micromechanical analysis of volume change behaviour due to cyclic temperature variations on sands
No full textThe contraction of sands subject to cyclic increases and reductions in temperature is of great practical importance; however, the effect of the initial packing condition and the mechanism underlying the behaviour are not completely understood. In this study, a thermal Discrete Element
Method (DEM) was developed by considering thermal expansion of particles and heat conduction through particles and interstitial pore fluids. Cyclic changes in temperature were simulated on samples with a variety of initial densities and degrees of anisotropy. The contraction of the soil skeleton was isolated from the thermal expansion of the particles using the “mechanical strain”
concept. Looser samples showed a larger mechanical strain accumulation, in line with observations in previous laboratory work. Highly anisotropic samples had a significant cyclic thermal contraction even in case of samples with a high density. Over the duration of the thermal cycles, a continuous decrease in fabric anisotropy was observed for the anisotropic samples, which may be associated with the fundamental mechanism underlying the cyclic thermal contraction of the sands
Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor
No full textSUMMARY Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian high-grade serous carcinoma (HGSC), particularly in homologous recombination-deficient tumors. However, the emergence of resistance poses a critical challenge, as over 50% of patients relapse within three years. The mechanisms underlying changes in PARP trapping, a central aspect of PARPi efficacy, are not well understood as current experimental methodologies lack resolution and throughput. To address this, we developed an intramolecular FRET-based biosensor by CRISPR-Cas9 dual-labelling endogenous PARP1 with EGFP and mCherryFP in OVCAR4 cells. This biosensor enables real-time, single-cell analysis of PARP trapping dynamics. Using fluorescence lifetime imaging microscopy (FLIM), we revealed dose-dependent PARP trapping, differentiated the trapping efficiencies of four clinically approved PARPi and observed reduced trapping in PARPi-resistant models in vitro and in vivo. This biosensor provides critical insights into PARPi resistance mechanisms, with implications for developing more effective therapies and advancing personalized treatment for ovarian cancer patients
Variation in arterial stiffness and markers of oxidative stress in patients with type 2 diabetes mellitus from different ethnic groups
No full textDiabetes is the world’s leading cause of renal and premature cardiovascular disease. There are marked differences between groups of patients with different ethnicities in their susceptibility to diabetes and its renal and cardiovascular complications. Novel markers of developing diabetes complications are related to disturbances in oxidative metabolism. In this cross-sectional study, we measured the arterial stiffness in patients of differing ethnicities with type 2 diabetes mellitus and assessed the relationship of their ethnicity with systemic markers of oxidative stress. Patients from black, African and Caribbean, and Asian minor ethnic groups were studied, with white patients with T2DM (n = 170) without evidence of cardiovascular disease (CVD). The vascular stiffness was measured by infrared finger-photoplethysmography. The oxidative stress burden was assessed by measuring the urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), activities of plasma glutathione peroxidase (GPx-3), superoxide dismutase (SOD) activities, and concentration of selenium. The vascular stiffness and 8-OHdG were higher in the white than in the Black patients (9.68 m/s vs. 9.26 m/s, p = 0.021 and 292.8 ng/mL vs. 200.9 ng/mL, p = 0.0027, respectively). Meanwhile, the GPx-3 and SOD activities and selenium were lower in the white than in the Black patients (283.3 U/L vs. 440.4 U/L, p < 0.0001; 37.5 U/L vs. 75.6 U/L, p = 0.0007; and 1.14 vs. 1.28 µmol/L, p = 0.0001, respectively). In regression modelling, the 8-OHdG/creatinine ratio was an independent predictor of vascular stiffness in the white patient group (β = 0.23 m/s per unit increase in ln(8-OHdG/creatinine) [95% CI, 0.03 to 0.42]; p = 0.021) but not in the Black patient group (p = 0.29). Increased vascular stiffness, lower endogenous antioxidant defense, and greater levels of oxidative damage were found in patients of white ethnicity, which could contribute to the higher incidence of CVD compared with patients from Black minor ethnic groups with diabetic renal disease
Barium calcium zirconium titanate thin film-based capacitive thermoelectric converter for low-grade waste heat
No full textA capacitive thermoelectric device can harvest thermal energy and convert it to electrical energy by employing a
15 temperature-dependent dielectric material whose permittivity sharply changes with temperature. Electricity can be generated by fluctuating the temperature of the capacitor. Currently, capacitive thermoelectric devices are not broadly used, which can be attributed to the low efficiency of the existing solutions, the lack of dielectric materials with suitable temperature non-linearity of the dielectric permittivity, and the complexity of modulating heat flux on the dielectric material. Here, we propose a device based on (Ba0.85Ca0.15)(Ti0.92Zr0.08)O3 and (Ba0.73Ca0.27)(Ti0.98Zr0.02)O3 thin films. The estimated power output under different operation conditions and dynamic workload of an Intel E5-2630 microprocessor show that these thin film materials are promising and can potentially be used for a capacitive thermoelectric converter
Evaluating public exposure to airborne particulates from major incident fires: a back trajectory plume modelling approach
No full textMajor incident fires at industrial facilities, particularly waste sites, pose a significant risk to public health because of the large amounts of hazardous airborne pollutants released into the ambient environment. Monitoring carried out during these fires is limited in spatial resolution, meaning that the full extent of population exposure is difficult to estimate. In this study, we overcome these limitations by using a novel back-trajectory plume modelling approach, applied to PM10 emission data from a significant tyre fire that occurred in the UK in 2010. This approach allows the calculation of an hourly emission rate that is then used in the forward modelling mode to predict hourly plume concentrations. An analysis of the modelled plume indicated that, as a reasonable worst case, up to 8000 residents in areas adjacent to the fire may have been exposed to PM10 concentrations that are deemed hazardous. Moreover, a vulnerability analysis showed that the exposed population had disproportionately poorer health than the national average, thus raising concerns about environmental justice. This work highlights the need to improve regulatory controls for waste sites located near urban areas and for further research on population exposure and the health impacts of major incident fires
Chirality-driven all-optical image differentiation
No full textOptical analog computing enables powerful functionalities, including spatial differentiation, image processing, and ultrafast linear operations. Yet, most existing approaches rely on resonant or periodic structures, whose performance is strongly wavelength-dependent, imposing bandwidth limitations and demanding stringent fabrication tolerances. Here, to address some of these challenges, we introduce a highly tunable platform for optical processing, composed of two cascaded uniform slabs exhibiting both circular and linear birefringence, whose response exhibits features relevant to optical processing without relying on resonances. Specifically, using a coupled-wave theory framework we show that sharp reflection minima, referred to as spectral holes, emerge from destructive interference between counter-propagating circularly polarized waves in uniform birefringent slabs, and can be engineered solely through parameter tuning without requiring any spatial periodicity. When operated in the negative-refraction regime enabled by giant chirality, the interference response acquires a highly parabolic form around the reflection minimum, giving rise to a polarization-selective Laplacian-like operator that performs accurate spatial differentiation over a broad spatial-frequency range. This functionality is demonstrated through an edge-detection proof of concept. The required material parameters align closely with recent experimental demonstrations of giant, tunable chirality via meta-optics, presenting a promising pathway towards compact and reconfigurable platforms for all-optical pattern recognition and image restoration
New insights into hydrogen-assisted intergranular cracking in nickel
No full textWe characterize the grain boundary (GB) susceptibility to hydrogen-assisted intergranular cracking in pure nickel as a function of coincident site lattice value (
-n), over a wide range of hydrogen concentrations (4 to 14 wppm). Cracks on the surface and within the bulk material were identified across the entire gauge region of the specimens. The susceptibility of GBs to crack initiation and propagation was evaluated by separating cracks containing single GB or multiple GBs. A larger loss in fracture strain, a smaller reduction in area, and an increase in the percentage of intergranular fracture indicated a higher degree of embrittlement at elevated hydrogen concentrations. The number of cracks was significantly higher on the surface than in the bulk for the most severe hydrogen charging conditions (
8 wppm), while a similar number was observed for lower concentrations. The propensity for hydrogen-assisted intergranular cracking at different types of GBs on the surface and in the bulk material was consistent, indicating that while cathodic charging can promote surface cracks, it does not significantly impact the GBs relative susceptibility. The
-3 boundaries were the most resistant to cracking, as evidenced by the considerably lower fraction of these GBs exhibiting intergranular cracking at all hydrogen concentrations considered. This contrasts literature findings for Ni alloys and can be explained by the segregation energies and reductions in the cohesive strength with hydrogen, with less favorable trapping at the
-3 boundaries. No evidence of plasticity-mediated cracking initiation was observed
Fractal Calibration for long-tailed object detection
No full textReal-world datasets follow an imbalanced distribution, which poses significant challenges in rare-category object detection. Recent studies tackle this problem by developing re-weighting and re-sampling methods, that utilise the class frequencies of the dataset. However, these techniques focus solely on the frequency statistics and ignore the distribution of the classes in image space, missing important information. In contrast to them, we propose FRActal CALibration (FRACAL): a novel post-calibration method for long-tailed object detection. FRACAL devises a logit adjustment method that utilises the fractal dimension to estimate how uniformly classes are distributed in image space. During inference, it uses the fractal dimension to inversely down-weight the probabilities of uniformly spaced class predictions achieving balance in two axes: between frequent and rare categories, and between uniformly spaced and sparsely spaced classes. FRACAL is a post-processing method and it does not require any training, also it can be combined with many off-the-shelf models such as one-stage sigmoid detectors and two-stage instance segmentation models. FRACAL boosts the rare class performance by up to 8.6% and surpasses all previous methods on LVIS dataset, while showing good generalisation to other datasets such as COCO, V3Det and OpenImages. We provide the code at https://github.com/kostas1515/FRACAL
Glucose variability and mode of anaesthesia in major noncardiac surgery (GlucoVITAL): study protocol for a randomised controlled trial
No full textBackground
Hyperglycaemia after noncardiac surgery occurs commonly and is associated with complications. The choice of maintenance anaesthesia may promote hyperglycaemia and increase glucose variability, both of which exacerbate inflammation and organ dysfunction. We hypothesise that total intravenous anaesthesia reduces glucose variability, particularly in individuals with insulin resistance or diabetes mellitus, and hence may reduce postoperative complications.
Methods
This multicentre, randomised controlled parallel group trial will recruit 450 participants ≥50 yr undergoing elective noncardiac surgery. Participants will be randomly allocated in a 1:1 ratio (with minimisation) to receive either total intravenous anaesthesia or inhalation agents (typically sevoflurane) for maintenance of anaesthesia. The primary outcome is blood glucose, measured at prespecified timepoints (before, immediately after, and the morning after surgery). Continuous glucose monitoring (CGM; Dexcom G7) will commence at induction of anaesthesia for up to 10 days after surgery (or hospital discharge) to establish the reliability and accuracy of CGM compared with blood glucose measurements. Secondary outcomes include days alive and out of hospital within 30 days of surgery and postoperative complications (Clavien–Dindo grade ≥2). Absolute glucose and CGM-derived measures of glucose variability will be compared between participants who sustain, or remain free of, myocardial injury within 24 h of surgery, infectious complications within 30 days of surgery, and vasopressor use persisting >4 h after surgery.
Conclusions
GlucoVITAL will establish whether the mode of anaesthesia may alter glucose control in susceptible individuals and also explore the role of glucose variability in organ injury after noncardiac surgery using CGM