Uterine spiral artery remodeling involves endothelial apoptosis induced by extravillous trophoblasts through Fas/FasL interactions.

Objective— Invasion of uterine spiral arteries by extravillous trophoblasts in the first trimester of pregnancy results in loss of endothelial and musculoelastic layers. This remodeling is crucial for an adequate blood supply to the fetus with a failure to remodel implicated in the etiology of the hypertensive disorder preeclampsia. The mechanism by which trophoblasts induce this key process is unknown. This study gives the first insights into the potential mechanisms involved. Methods and Results— Spiral arteries were dissected from nonplacental bed biopsies obtained at Caesarean section, and a novel model was used to mimic in vivo events. Arteries were cultured with trophoblasts in the lumen, and apoptotic changes in the endothelial layer were detected after 20 hours, leading to loss of endothelium by 96 hours. In vitro, coculture experiments showed that trophoblasts stimulated apoptosis of primary decidual endothelial cells and an endothelial cell line. This was blocked by caspase inhibition and NOK2, a FasL blocking antibody. NOK2 also abrogated trophoblast-induced endothelial apoptosis in the vessel model. Conclusions— Extravillous trophoblast induction of endothelial apoptosis is a possible mechanism by which the endothelium is removed, and vascular remodeling may occur in uterine spiral arteries. Fas/FasL interactions have an important role in trophoblast-induced endothelial apoptosis

Optimisation of air cooled, open-cathode fuel cells: Current of lowest resistance and electro-thermal performance mapping

Selecting the ideal operating point for a fuel cell depends on the application and consequent trade-off between efficiency, power density and various operating considerations. A systematic methodology for determining the optimal operating point for fuel cells is lacking; there is also the need for a single-value metric to describe and compare fuel cell performance. This work shows how the ‘current of lowest resistance’ can be accurately measured using electrochemical impedance spectroscopy and used as a useful metric of fuel cell performance. This, along with other measures, is then used to generate an ‘electro-thermal performance map’ of fuel cell operation. A commercial air-cooled open-cathode fuel cell is used to demonstrate how the approach can be used; in this case leading to the identification of the optimum operating temperature of ∼45 °C

Clinical and diagnostic features of Bartter and Gitelman syndromes

Background: Bartter and Gitelman syndromes are autosomal recessive disorders of renal tubular salt handling. Due to their rarity, limited long-term data are available to inform prognosis and management. / Methods: Long-term longitudinal data were analysed for 45 children with pathogenic variants in SLC12A1 (n = 8), KCNJ1 (n = 8), CLCNKB (n = 17), BSND (n = 2) and SLC12A3 (n = 10) seen at a single centre between 1984 and 2014. Median follow-up was 8.9 [interquartile range (IQR) 0.7–18.1] years. / Results: Polyhydramnios and prematurity were seen in children with SLC12A1 and KCNJ1 mutations. Patients with CLCNKB mutations had the lowest serum potassium and serum magnesium and the highest serum bicarbonate levels. Fractional excretion of chloride was >0.5% in all patients prior to supplementation. Nephrocalcinosis at presentation was present in the majority of patients with SLC12A1 and KCNJ1 mutations, while it was only present in one patient with CLCNKB and not in SLC12A3 or BSND mutations. Growth was impaired, but within the normal range (median height standard deviation score −1.2 at the last follow-up). Impaired estimated glomerular filtration rate (eGFR <90 mL/min/1.73 m2) at the last follow-up was seen predominantly with SLC12A1 [71 mL/min/1.73 m2 (IQR 46–74)] and KCNJ1 [62 mL/min/1.73 m2 (IQR 48–72)] mutations. Pathological albuminuria was detected in 31/45 children. / Conclusions: Patients with Bartter and Gitelman syndromes had a satisfactory prognosis during childhood. However, decreased eGFR and pathologic proteinuria was evident in a large number of these patients, highlighting the need to monitor glomerular as well as tubular function. Electrolyte abnormalities were most severe in CLCNKB mutations both at presentation and during follow-up. Fractional excretion of chloride prior to supplementation is a useful screening investigation in children with hypokalaemic alkalosis to establish renal salt wasting

Quantifying the effects of wave-current interactions on tidal energy resource at sites in the English Channel using coupled numerical simulations

This is the final version. Available on open access from MDPI via the DOI in this recordNumerical modeling of currents and waves is used throughout the marine energy industry for resource assessment. This study compared the output of numerical flow simulations run both as a standalone model and as a two-way coupled wave–current simulation. A regional coupled flow-wave model was established covering the English Channel using the Delft D-Flow 2D model coupled with a SWAN spectral wave model. Outputs were analyzed at three tidal energy sites: Alderney Race, Big Roussel (Guernsey), and PTEC (Isle of Wight). The difference in the power in the tidal flow between coupled and standalone model runs was strongly correlated to the relative direction of the waves and currents. The net difference between the coupled and standalone runs was less than 2.5%. However, when wave and current directions were aligned, the mean flow power was increased by up to 7%, whereas, when the directions were opposed, the mean flow power was reduced by as much as 9.6%. The D-Flow Flexible Mesh model incorporates the effects of waves into the flow calculations in three areas: Stokes drift, forcing by radiation stress gradients, and enhancement of the bed shear stress. Each of these mechanisms is discussed. Forcing from radiation stress gradients is shown to be the dominant mechanism affecting the flow conditions at the sites considered, primarily caused by dissipation of wave energy due to white-capping. Wave action is an important consideration at tidal energy sites. Although the net impact on the flow power was found to be small for the present sites, the effect is site specific and may be significant at sites with large wave exposure or strong asymmetry in the flow conditions and should thus be considered for detailed resource and engineering assessments.European Regional Development Fund (ERDF

The Hydro-electro-thermal Performance of Air-cooled, Open-cathode Polymer Electrolyte Fuel Cells: Combined Localised Current Density, Temperature and Water Mapping

In situ diagnostic techniques provide a means of understanding the internal workings of fuel cells so that improved designs and operating regimes can be identified. Here, a novel metrology approach is reported that combines current and temperature mapping with water visualisation using neutron radiography. The approach enables a hydro-electro-thermal performance map to be generated that is applied to an air-cooled, open-cathode polymer electrolyte fuel cell. This type of fuel cell exhibits a particularly interesting coupled relationship between water, current and heat, as the air supply has the due role of cooling the stack as well as providing the cathode reactant feed via a single source. It is found that water predominantly accumulates under the cooling channels (thickness of 70-100 μm under the cooling channels and 5-25 μm in the active channels at 0.5 A cm−2), in a similar fashion to the lands in a closed-cathode design, but contrary to passive open-cathode systems. The relationship between current, temperature and water accumulation is complex and highly dependent on location within the cell. However, there is a general trend that higher currents and cooling limitations, especially above 0.7 A cm−2 and below 3.9 × 10−3 m3 s−1, leads to temperatures above 60 °C, which dehydrate the membrane (water thickness of 10-25 um) and the cell operates below 0.5 V

Nitrogen Blanketing and Hydrogen Starvation in Dead-Ended-Anode Polymer Electrolyte Fuel Cells Revealed by Hydro-Electro-Thermal Analysis

Dead-ended anode operation has a number of practical advantages that simplify system complexity and lower cost for polymer electrolyte fuel cells. However, dead-ended mode leads to performance loss over time which can only be reversed by performing intermittent purge events. This work applies a combined hydro-electro-thermal analysis to an air-cooled open-cathode fuel cell, presenting experimental functional maps of water distribution, current density and temperature. This approach has allowed the identification of a 'nitrogen blanketing' effect due to nitrogen cross-over from the cathode and a 'bypass' effect where a peripheral gap between the gasket and the GDL offers a hydrogen flow 'short circuit' to the border of the electrode. A consequence of high local current density at the margin of the electrode, and resulting high temperatures, may impact the lifetime of the cell in dead-end mode

Mixed molybdenum and vanadium oxide nanoparticles with excellent high-power performance as Li-ion battery negative electrodes

Several nano-sized mixed molybdenum/vanadium oxide monoclinic solid solutions were synthesised using a continuous hydrothermal flow process and studied with a wide range of physical characterization techniques including X-ray photoelectron spectroscopy, X-ray diffraction, transmission electron microscopy and X-ray absorption spectroscopy. The nanomaterials were tested as anodes for Li-ion batteries in the potential range 0.05–3.00 V vs. Li/Li+. Samples with nominal formulas of Mo0.5V0.5O2 and Mo0.33V0.67O2 showed excellent performance, especially at high current rates, due to their highly pseudocapacitive charge storage mechanism. At a specific current of 10 A g−1, Mo0.5V0.5O2 and Mo0.33V0.67O2 showed specific capacities of ca. 200 and 170 mAh g−1, respectively. Mo0.5V0.5O2 also showed good cyclability, with a specific capacity of 480 mAh g−1 after 150 cycles at a specific current of 0.5 A g−1. For cyclic voltammetries conducted at high scan rates, pseudocapacitive charge storage contributed more than 90% to the total charge storage for both samples. The scalability of the synthesis technique and excellent electrochemical performance at high power, make these materials promising as negative electrode active materials for Li-ion batteries

Combined current and temperature mapping in an air-cooled, open-cathode polymer electrolyte fuel cell under steady-state and dynamic conditions

In situ diagnostic techniques provide a means of understanding the internal workings of fuel cells so that improved designs and operating regimes can be identified. Here, for the first time, a combined current density and temperature distributed measurement system is used to generate an electro-thermal performance map of an air-cooled, air-breathing polymer electrolyte fuel cell stack operating in an air/hydrogen cross-flow configuration. Analysis is performed in low- and high-current regimes and a complex relationship between localised current density, temperature and reactant supply is identified that describes the way in which the system enters limiting performance conditions. Spatiotemporal analysis was carried out to characterise transient operations in dead-ended anode/purge mode which revealed extensive current density and temperature gradients

Association of Serum Brain-Derived Tau With Clinical Outcome and Longitudinal Change in Patients With Severe Traumatic Brain Injury

Importance: Blood-based measurements of total tau (T-tau) are commonly used to examine neuronal injury in patients with traumatic brain injury (TBI), but current assays do not differentiate between brain-derived tau (BD-tau) and tau produced in peripheral tissues. A novel assay for BD-tau has recently been reported that selectively quantifies nonphosphorylated tau of central nervous system origin in blood samples. Objectives: To examine the association of serum BD-tau with clinical outcomes in patients with severe TBI (sTBI) and its longitudinal changes over 1 year. Design, Setting, and Participants: This prospective cohort study was conducted at the neurointensive unit at the Sahlgrenska University Hospital, Gothenburg, Sweden, between September 1, 2006, and July 1, 2015. The study included 39 patients with sTBI followed up for up to 1 year. Statistical analysis was performed between October and November 2021. Exposures: Serum BD-tau, T-tau, phosphorylated tau231 (p-tau231), and neurofilament light chain (NfL) measured on days 0, 7, and 365 after injury. Main Outcomes and Measures: Associations of serum biomarkers with clinical outcome and longitudinal change in sTBI. Severity of sTBI was evaluated using the Glasgow Coma Scale at hospital admission, while clinical outcome was assessed with the Glasgow Outcome Scale (GOS) at 1-year follow-up. Participants were classified as having a favorable outcome (GOS score, 4-5) or unfavorable outcome (GOS score, 1-3). Results: Among the 39 patients (median age at admission, 36 years [IQR, 22-54 years]; 26 men [66.7%]) in the study on day 0, the mean (SD) serum BD-tau level was higher among patients with unfavorable outcomes vs those with favorable outcomes (191.4 [190.8] pg/mL vs 75.6 [60.3] pg/mL; mean difference, 115.9 pg/mL [95% CI, 25.7-206.1 pg/mL]), while the other markers had smaller between-group mean differences (serum T-tau, 60.3 pg/mL [95% CI, -22.0 to 142.7 pg/mL]; serum p-tau231, 8.3 pg/mL [95% CI, -6.4 to 23.0 pg/mL]; serum NfL, -5.4 pg/mL [95% CI, -99.0 to 88.3 pg/mL]). Similar results were recorded on day 7. Longitudinally, baseline serum BD-tau concentrations showed slower decreases in the whole cohort (42.2% on day 7 [from 138.6 to 80.1 pg/mL] and 93.0% on day 365 [from 138.6 to 9.7 pg/mL]) compared with serum T-tau (81.5% on day 7 [from 57.3 to 10.6 pg/mL] and 99.0% on day 365 [from 57.3 to 0.6 pg/mL]) and p-tau231 (92.5% on day 7 [from 20.1 to 1.5 pg/mL] and 95.0% on day 365 [from 20.1 to 1.0 pg/mL]). These results did not change when considering clinical outcome, where T-tau decreased twice as fast as BD-tau in both groups. Similar results were obtained for p-tau231. Furthermore, the biomarker levels on day 365 were lower, compared with day 7, for BD-tau but not T-tau or p-tau231. Serum NfL had a different trajectory to the tau biomarkers, with levels increasing by 255.9% on day 7 compared with day 0 (from 86.8 to 308.9 pg/mL) but decreasing by 97.0% by day 365 vs day 7 (from 308.9 to 9.2 pg/mL). Conclusions and Relevance: This study suggests that serum BD-tau, T-tau, and p-tau231 have differential associations with clinical outcome and 1-year longitudinal change in patients with sTBI. Serum BD-tau demonstrated utility as a biomarker to monitor outcomes in sTBI and can provide valuable information regarding acute neuronal damage

Incidence of community-acquired lower respiratory tract infections and pneumonia among older adults in the United Kingdom: a population-based study.

Community-acquired lower respiratory tract infections (LRTI) and pneumonia (CAP) are common causes of morbidity and mortality among those aged ≥65 years; a growing population in many countries. Detailed incidence estimates for these infections among older adults in the United Kingdom (UK) are lacking. We used electronic general practice records from the Clinical Practice Research Data link, linked to Hospital Episode Statistics inpatient data, to estimate incidence of community-acquired LRTI and CAP among UK older adults between April 1997-March 2011, by age, sex, region and deprivation quintile. Levels of antibiotic prescribing were also assessed. LRTI incidence increased with fluctuations over time, was higher in men than women aged ≥70 and increased with age from 92.21 episodes/1000 person-years (65-69 years) to 187.91/1000 (85-89 years). CAP incidence increased more markedly with age, from 2.81 to 21.81 episodes/1000 person-years respectively, and was higher among men. For both infection groups, increases over time were attenuated after age-standardisation, indicating that these rises were largely due to population aging. Rates among those in the most deprived quintile were around 70% higher than the least deprived and were generally higher in the North of England. GP antibiotic prescribing rates were high for LRTI but lower for CAP (mostly due to immediate hospitalisation). This is the first study to provide long-term detailed incidence estimates of community-acquired LRTI and CAP in UK older individuals, taking person-time at risk into account. The summary incidence commonly presented for the ≥65 age group considerably underestimates LRTI/CAP rates, particularly among older individuals within this group. Our methodology and findings are likely to be highly relevant to health planners and researchers in other countries with aging populations