Cyclic nucleotide-dependent relaxation in human umbilical vessels

Umbilical vessels have a low sensitivity to dilate, and this property is speculated to have physiological implications. We aimed to investigate the different relaxing responses of human umbilical arteries (HUAs) and veins (HUVs) to agonists acting through the cAMP and cGMP pathways. Vascular rings were suspended in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U44069, concentration-response curves to the nitric oxide (NO) donor sodium nitroprusside (SNP), the soluble guanylate cyclase (sGC) stimulator BAY 41-2272, the adenylate cyclase (AC) activator forskolin, the \u3b2-adrenergic receptor agonists isoproterenol (ADRB1), salmeterol (ADRB2), and BRL37344 (ADRB3), and the phosphodiesterase (PDE) inhibitors milrinone (PDE3), rolipram (PDE4), and sildenafil (PDE5) were performed. None of the tested drugs induced a relaxation higher than 30% of the U44069-induced tone. Rings from HUAs and HUVs showed a similar relaxation to forskolin, SNP, PDE inhibitors, and ADRB agonists. BAY 41-2272 was significantly more efficient in relaxing veins than arteries. ADRB agonists evoked weak relaxations (< 20%), which were impaired in endothelium-removed vessels or in the presence of the NO synthase inhibitor L-NAME, sGC inhibitor ODQ. PKA and PKG inhibitors impaired ADBR1-mediated relaxation but did not affect ADRB2-mediated relaxation. ADRB3-mediated relaxation was impaired by PKG inhibition in HUAs and by PKA inhibition in HUVs. Although HUA and HUV rings were relaxed by BRL37344, immunohistochemistry and RT-qPCR analysis showed that, compared to ADRB1 and ADRB2, ADRB3 receptors are weakly or not expressed in umbilical vessels. In conclusion, our study confirmed the low relaxing capacity of HUAs and HUVs from term infants. ADRB-induced relaxation is partially mediated by endothelium-derived NO pathway in human umbilical vessels

Party Face Congratulations! Exploring Design Ideas to Help Sighted Users with Emoji Accessibility when Messaging with Screen Reader Users

Emoji are a popular, expressive form of non-verbal communication. However, people often use emoji in ways that result in confusing or cumbersome screen reader output. We created two accessibility support designs: (1) Preview, which displays a basic text transcript of a message with emoji that a screen reader would narrate, and (2) Alert, which summarises potential accessibility issues caused by emoji within a message. We explored our designs using an online survey and provided participants with the option to edit messages that contained emoji, should they choose to do so. We collected 1508 modified messages from 116 sighted participants and conducted a qualitative analysis of the data to identify the strategies participants used when asked to edit a message for accessibility issues and their appreciation of each design. We found that participants preferred the Preview design over Alert since it allows for subjective interpretations of what constitutes an accessible message. We report sighted users' rewriting strategies (e.g., editing the message to move the emoji to the end) and incorrect assumptions about screen readers that would lead to using textual markers that are incompatible with screen readers. We discuss the design implications for future systems for accessible messaging

A new case manager for diabetic patients: a pilot observational study of the role of community pharmacists and pharmacy services in the case management of diabetic patients

The adherence of type 2 diabetes mellitus (DM2) patients with an individual care plan (ICP) is often not satisfactory, nor does it allow for a significant improvement in outcome, because of poor accessibility to services, poor integration of pathway articulations, poor reconciliation with the patient's life, or the lack of a constant reference person. The purpose of this study was to evaluate the contribution of community pharmacists and pharmacy services in improving adherence with periodic controls in DM2. The study was conducted at a rural pharmacy. A sample of 40 patients was calculated with respect to a historical cohort and subsequently enrolled. Clinical and personal data were collected in an electronic case report form. Pharmacists acting as a case manager followed patients carrying out their ICP developed by an attending physician. Some of the activities foreseen by the ICP, such as electrocardiogram, fundus examination, and self-analysis of blood and urine, were carried out directly in the pharmacy by the pharmacist through the use of telemedicine services and point of care units. Activities that could not be performed in the pharmacy were booked by the pharmacist at the accredited units. Examination results were electronically reported by the pharmacist to the attending physician. The primary endpoint was the variation in patient adherence with the ICP compared to a historical cohort. Secondary endpoints were variation in waiting time for the examinations, mean percentage change in glycated hemoglobin (HbA1c) and low-density lipoprotein (LDL) cholesterol levels and blood pressure, impact on healthcare-related costs, and perceived quality of care. Adherence to the ICP significantly increased. Waiting times were reduced and clinical outcomes improved with conceivable effects on costs. Patients appreciated the easier access to services. Community pharmacists and pharmacy services represent ideal actors and context that, integrated in the care network, can really favor ICP adherence and obtain daily morbidity reduction and cost savings through proper disease control and an early diagnosis of complications

A Simplex-Based Extension of Fourier-Motzkin for Solving Linear Integer Arithmetic

International audienceThis paper describes a novel decision procedure for quantifier-free linear integer arithmetic. Standard techniques usually relax the initial problem to the rational domain and then proceed either by projection (e.g. Omega-Test) or by branching/cutting methods (branch-and-bound, branch-and-cut, Gomory cuts). Our approach tries to bridge the gap between the two techniques: it interleaves an exhaustive search for a model with bounds inference. These bounds are computed provided an oracle capable of finding constant positive linear combinations of affine forms. We also show how to design an efficient oracle based on the Simplex procedure. Our algorithm is proved sound, complete, and terminating and is implemented in the Alt-Ergo theorem prover. Experimental results are promising and show that our approach is competitive with state-of-the-art SMT solvers

Only females in poor condition display a clear preference and prefer males with an average badge

<p>Abstract</p> <p>Background</p> <p>Female condition-dependent variation in mate preference may have important evolutionary implications, not only within the same population but also among populations. There are few experiments, however, on how condition and/or genotype influences female mate preferences. The black throat patch of the male house sparrow, <it>Passer domesticus</it>, is an intensively studied plumage trait. It is often referred to as a 'badge of status' and seems to be involved in female mate choice, but differences exist among populations. Between-population variation in mate preference may occur for condition-dependent mate preferences. We tested the hypothesis that female preference may vary with female quality (body condition). Therefore, we measured female preference for badge size using an aviary two-choice test in which females were presented with two males that had different sizes of badges (enlarged or averaged).</p> <p>Results</p> <p>Overall we did not find a female preference for enlarged or average badges, but low-quality females spent more time near average badge males. Conversely, high-quality females did not show a clear preference.</p> <p>Conclusions</p> <p>Collectively, these results indicate that female preference varies with female quality. Differences in female condition are causes of within-population variation in mating preferences. To our knowledge, our results provide one of the first experimental evidences that variation in preference for a male ornament is associated with female condition. In our study, however, only females of low condition displayed a clear mate preference. Differences observed among populations could be partly explained by differences in female condition.</p

Intersection and Rotation of Assumption Literals Boosts Bug-Finding

SAT-based techniques comprise the state-of-the-art in functional verification of safety-critical hardware and software, including IC3/PDR-based model checking and Bounded Model Checking (BMC). BMC is the incontrovertible best method for unsafety checking, aka bug-finding. Complementary Approximate Reachability (CAR) and IC3/PDR complement BMC for bug-finding by detecting different sets of bugs. To boost the efficiency of formal verification, we introduce heuristics involving intersection and rotation of the assumption literals used in the SAT encodings of these techniques. The heuristics generate smaller unsat cores and diverse satisfying assignments that help in faster convergence of these techniques, and have negligible runtime overhead. We detail these heuristics, incorporate them in CAR, and perform an extensive experimental evaluation of their performance, showing a 25% boost in bug-finding efficiency of CAR.We contribute a detailed analysis of the effectiveness of these heuristics: their influence on SAT-based bug-finding enables detection of different bugs from BMCbased checking. We find the new heuristics are applicable to IC3/PDR-based algorithms as well, and contribute a modified clause generalization procedure

Home, dirty home: effect of old nest material on nest-site selection and breeding performance in a cavity-nesting raptor

The quality of a breeding site may have major fitness consequences. A fundamental step to understanding the process of nest-site selection is the identification of the information individuals use to choose high-quality nest sites. For secondary cavity-nesting bird species that do not add nest lining material, organic remains (faeces, pellets) accumulated inside nest cavities during previous breeding events may be a cue for high-quality nest-sites, as they contain information about past successful breeding and may improve thermal insulation of eggs during incubation. However, cavities in which breeding was successful might also contain more nest-dwelling ectoparasites than unoccupied cavities, offering an incentive for prospective parents to avoid them. We exposed breeding cavity-nesting lesser kestrels (Falco naumanni) to nestbox dyads consisting of a dirty (with a thick layer of organic substrate) and a clean nestbox (without organic material). Dirty nestboxes were strongly preferred, being occupied earlier and more frequently than clean ones. Hatching success in dirty nestboxes was significantly higher than in clean ones, suggesting a positive effect of organic nest material on incubation efficiency, while nestbox dirtiness did not significantly affect clutch and brood size. Nestlings from dirty nestboxes had significantly higher ectoparasite load than those from clean nestboxes soon after egg hatching, but this difference was not evident a few days later. Nest substrate did not significantly affect nestling growth. We concluded that nest substrate is a key driver of nest-site choice in lesser kestrels, although the adaptive value of such a strong preference appears elusive and may be context-dependent

A maChine and deep Learning Approach to predict pulmoNary hyperteNsIon in newbornS with congenital diaphragmatic Hernia (CLANNISH): Protocol for a retrospective study

Introduction Outcome predictions of patients with congenital diaphragmatic hernia (CDH) still have some limitations in the prenatal estimate of postnatal pulmonary hypertension (PH). We propose applying Machine Learning (ML), and Deep Learning (DL) approaches to fetuses and newborns with CDH to develop forecasting models in prenatal epoch, based on the integrated analysis of clinical data, to provide neonatal PH as the first outcome and, possibly: Favorable response to fetal endoscopic tracheal occlusion (FETO), need for Extracorporeal Membrane Oxygenation (ECMO), survival to ECMO, and death. Moreover, we plan to produce a (semi)automatic fetus lung segmentation system in Magnetic Resonance Imaging (MRI), which will be useful during project implementation but will also be an important tool itself to standardize lung volume measures for CDH fetuses. Methods and analytics Patients with isolated CDH from singleton pregnancies will be enrolled, whose prenatal checks were performed at the Fetal Surgery Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milan, Italy) from the 30th week of gestation. A retrospective data collection of clinical and radiological variables from newborns' and mothers' clinical records will be performed for eligible patients born between 01/01/2012 and 31/12/2020. The native sequences from fetal magnetic resonance imaging (MRI) will be collected. Data from different sources will be integrated and analyzed using ML and DL, and forecasting algorithms will be developed for each outcome. Methods of data augmentation and dimensionality reduction (feature selection and extraction) will be employed to increase sample size and avoid overfitting. A software system for automatic fetal lung volume segmentation in MRI based on the DL 3D U-NET approach will also be developed. Ethics and dissemination This retrospective study received approval from the local ethics committee (Milan Area 2, Italy). The development of predictive models in CDH outcomes will provide a key contribution in disease prediction, early targeted interventions, and personalized management, with an overall improvement in care quality, resource allocation, healthcare, and family savings. Our findings will be validated in a future prospective multicenter cohort study

Heart rate and arterial pressure changes during whole-body deep hypothermia

Whole-body deep hypothermia (DH) could be a new therapeutic strategy for asphyxiated newborn. This retrospective study describes how DH modified the heart rate and arterial blood pressure if compared to mild hypothermia (MH). Fourteen in DH and 17 in MH were cooled within the first six hours of life and for the following 72 hours. Hypothermia criteria were gestational age 6536 weeks; birth weight 651800\u2009g; clinical signs of moderate/severe hypoxic-ischemic encephalopathy. Rewarming was obtained in the following 6-12 hours (0.5\ub0C/h) after cooling. Heart rates were the same between the two groups; there was statistically significant difference at the beginning of hypothermia and during rewarming. Three babies in the DH group and 2 in the MH group showed HR 520\u2009ms. Infant submitted to deep hypothermia had not bradycardia or Qtc elongation before cooling and after rewarming. Blood pressure was significantly lower in DH compared to MH during the cooling, and peculiar was the hypotension during rewarming in DH group. Conclusion. The deeper hypothermia is a safe and feasible, only if it is performed by a well-trained team. DH should only be associated with a clinical trial and prospective randomized trials to validate its us