Abstract Spermatogenesis in Lake Magadi tilapia ( Alcolapia grahami ), a cichlid fish endemic to the highly alkaline and saline Lake Magadi in Kenya, was evaluated using light and transmission ...electron microscopy. Spermatogenesis, typified by its three major phases (spermatocytogenesis, meiosis and spermiogenesis), was demonstrated by the presence of maturational spermatogenic cells namely spermatogonia, spermatocytes, spermatids and spermatozoa. Primary spermatogonia, the largest of all the germ cells, underwent a series of mitotic divisions producing primary spermatocytes, which then entered two consecutive meiotic divisions to produce secondary spermatocytes and spermatids. Spermatids, in turn, passed through three structurally distinct developmental stages typical of type-I spermiogenesis to yield typical primitive anacrosomal spermatozoa of the externally fertilizing type (aquasperm). The spermatozoon of this fish exhibited a spheroidal head with the nucleus containing highly electron-dense chromatin globules, a midpiece containing ten ovoid mitochondria arranged in two rows and a flagellum formed by the typical 9 + 2 microtubule axoneme. In addition, the midpiece, with no cytoplasmic sheath, appeared to end blindly distally in a lobe-like pattern around the flagellum; a feature that was unique and considered adaptive for the spermatozoon of this species to the harsh external environment. These observations show that the testis of A. grahami often undergoes active spermatogenesis despite the harsh environmental conditions to which it is exposed on a daily basis within the lake. Further, the spermiogenic features and spermatozoal ultrastructure appear to be characteristic of Cichlidae and, therefore, may be of phylogenetic significance.
A prototype for a sampling calorimeter made out of cerium fluoride crystals interleaved with tungsten plates, and read out by wavelength-shifting fibres, has been exposed to beams of electrons with ...energies between 20 and 150GeV, produced by the CERN Super Proton Synchrotron accelerator complex. The performance of the prototype is presented and compared to that of a Geant4 simulation of the apparatus. Particular emphasis is given to the response uniformity across the channel front face, and to the prototype׳s energy resolution.
Abstract Background There are limited effective treatment options for persistent atrial fibrillation (AF) patients, with pulmonary veins (PV) isolation alone being considered suboptimal for many ...patients. Hybrid convergent ablation has been shown to improve clinical outcomes when compared to an endocardial-only radiofrequency (RF) strategy. Pulsed field ablation (PFA) has recently gained growing interest for its efficacy and safety profile in PV and posterior wall (PW) ablation. Objectives To compare clinical outcomes of hybrid convergent RF ablation versus endocardial PFA for PV and PW isolation in patients with persistent AF. Methods From July 2022, 86 persistent AF consecutive patients, receiving endocardial PFA of PV and PW (PFA group, N = 44) or receiving hybrid convergent RF ablation (Hybrid group, N = 42) at our institution were enrolled. Recurrence was defined as any atrial tachyarrhythmia following the 3-month blanking period. Results No differences were found between PFA and Hybrid groups regarding age (PFA 66.0±7.4 years vs Hybrid 63.9±10.6 years; p=0.193) and left atrial volume index (PFA 45.5 36.7-57.2 ml/m² vs Hybrid 45.0 39.2-59.7 ml/m²; p=0.920). Differences regarding left ventricular ejection fraction were borderline significant among groups (PFA 55.0 49.5-62.0% vs Hybrid 60.5 52.3-65.0%; p=0.048), both showing an overall normal LV function. There were no significant differences regarding AF duration (PFA 38.0 months IQR: 19.2 to 99.0 months vs Hybrid 70.0 months IQR: 46.0 to 118.0 months; p = 0.063). Redo ablation patients’ rate was higher in the hybrid group (PFA n=16, 36.4% vs Hybrid n=28, 66.6%; p<0.001). Procedure duration was Ionger in the hybrid group (179.9±60.1 minutes) compared to PFA endocardial ablation (PFA 106.2±30.7 minute; p<0.01). After a median follow-up of 233.0 179.0–331.8 days, there was no difference in atrial tachyarrhythmias recurrence rate (PFA n=11, 25.0% vs Hybrid n=10, 23.8%; p=0.897); no difference in the antiarrhythmic drug use rate was found (PFA n=24, 54.5% vs Hybrid n=19, 45.2%; p=0.388). Conclusions PFA of PV and PW, compared with the hybrid convergent ablation strategy, is an endocardial-only, less invasive, and faster procedure. 6-month rhythm outcomes were similar in both groups.
Lot of efforts have been devoted by ATLAS and CMS teams to improve the quality of LHC events analysis with the Matrix Element Method (MEM). Up to now, very few implementations try to face up the huge ...computing resources required by this method. We propose here a highly parallel version, combining MPI and OpenCL, which makes the MEM exploitation reachable for the whole CMS datasets with a moderate cost. In the article, we describe the status of two software projects under development, one focused on physics and one focused on computing. We also showcase their preliminary performance obtained with classical multi-core processors, CUDA accelerators and MIC co-processors. This let us extrapolate that with the help of 6 high-end accelerators, we should be able to reprocess the whole LHC run 1 within 10 days, and that we have a satisfying metric for the upcoming run 2. The future work will consist in finalizing a single merged system including all the physics and all the parallelism infrastructure, thus optimizing implementation for best hardware platforms.
Introduction: Carbapenem-resistant organisms (CROs) present a serious public health problem. Limited treatment options has led to increased use of colistin and polymyxin. Since 2014, the US Food and ...Drug Administration approved 4 new beta-lactam beta-lactamase inhibitor (BLBLI) combination antibiotics with activity against CROs. These new antibiotics have been shown to be more effective and less toxic than colistin and polymyxin but are considerably more expensive. This study evaluated the cost-effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Methods: A decision-tree microsimulation model was used to evaluate the cost effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Treatment groups differed in risk of mortality and risk of an acute kidney injury (AKI). The relative risk of mortality was determined by creating a meta-analysis comparing new BLBLIs to colistin. Cost inputs included medication costs and the cost to treat an AKI. The primary outcomes include quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). Model inputs included: clinical outcomes and adverse events (30-day mortality and AKI); cost of treatment and adverse drug events; and health utilities. A 3% discount was applied for outcomes. A lifetime horizon was used from the perspective of the US healthcare system with a willingness-to-pay (WTP) threshold of $100 000. A sensitivity analysis was done to incorporate uncertainty. Results: The meta-analysis found the treatment with a new BLBLI was associated with a 50% decrease in the relative risk of 30-day mortality compared to colistin (RR 0.47, 95% CI 0.25-0.88). Treatment with a new BLBLI cost $16 200 and produced 11.5 QALYs, on average. The average colistin based regimen cost $3500 and produced 8.3 QALYs. The new BLBLIs were determined to be cost-effective with an ICER of $3900 per QALY gained. Treatment with a BLBLI remained cost-effective under all uncertainty scenarios tested. Conclusion: New BLBLIs are cost-effective compared to colistin for the treatment of CROs and are associated with improved mortality and fewer AKI events. The use of colistin should be reserved for cases where new BLBLIs are not available or there is documented resistance to these new antibiotics.
Abstract
Purpose
The purpose of this study was to improve antimicrobial management and outcomes of critically ill patients with community-acquired pneumonia (CAP) through implementation of a ...pharmacist-driven bundle for ordering evidence-based diagnostic tests in a medical intensive care unit (MICU).
Methods
An inpatient collaborative practice agreement (CPA) was established for MICU pharmacists to order criteria-driven diagnostic testing for CAP from November 2017–March 2018. Adults admitted to the MICU and started on empiric antibiotics for CAP were included. The intervention arm was compared with a standard of care (SOC) group from November 2016–March 2017.
Results
Ninety-one patients were included in each group. There was no difference in the median antibiotic duration between SOC and CPA, at 7 days (interquartile range IQR, 6–10) versus 7 days (IQR, 6–8), respectively. The overall use of evidence-based diagnostic tests increased in the CPA group. Patients in the CPA group had more frequent pathogen identification (SOC and CPA, respectively: 31 34% versus 46 51%, p = 0.035) and antimicrobial deescalation (24 26% versus 53 58%, p < 0.001). There was no significant difference in length of intensive care unit stay, at 4 days for SOC (IQR, 2–10) versus 6 days for CPA (IQR, 3–10), and no significant difference in inpatient all-cause mortality (13 14% versus 7 8%), retreatment 14 15% versus 11 12%), or 30-day readmission 16 (18% versus 13 14%) for SOC and CPA, respectively. The CPA was the only variable that was independently associated with antimicrobial deescalation (odds ratio, 4.030; 95% confidence interval, 2.101–7.731) in a multiple logistic regression.
Conclusion
Implementation of a pharmacy-driven pneumonia diagnostic stewardship bundle improved the use of evidence-based diagnostics and increased the frequency of pathogen identification. This intervention was associated with increased antimicrobial deescalation without a negative impact on patient safety outcomes.
The European eel is a highly migratory fish. After the reproduction in the Sargasso Sea early larval-stages start a passive ocean migration towards European and Mediterranean continental waters. ...After several years as yellow eels, mature adults change to silver stage and then start their return trip. The trajectory of their backward migration is unknown, because of low probability of capturing migrating individuals, having this capture never been reported in the Mediterranean. Recently, 8 silver eels were collected in the Strait of Sicily. Using literature information about possible individual route and speed, their geographical position was projected up to the spawning site during reproductive season. Despite using optimal and continuous migration swimming speed, none of the specimens may have been able to reach the Sargasso Sea in time for mating. Subsequently, to identify putative Mediterranean areas from which eels could have been reaching the spawning grounds on time, a backward scenario was postulated using the previous scientific assumptions. Our results suggests that just a small quota of Mediterranean silver males successfully reaches the Sargasso area, and only females from the westernmost and central parts of the basin could be able to fruitfully pond their eggs during the supposed spawning period.
Developing countries suffer with the growth of the so-called irregular cities. The lack of basic infrastructure and the inadequate urban growth management lead to urban flood problems. The concept of ...risk combines the probability of a hazard event with the consequences inflicted to a system. Thus, there are several possibilities of acting in flood risk mitigation: reducing the hazard and/or the system vulnerability. In this context, both structural measures and non-structural measures may be used. Traditional structural measures frequently were associated with river canalisation, dykes and dams. In the last past decades, the concepts of sustainable drainage systems have arisen, tending to control onsource runoff generation. The urban occupation of the city is very dense, with few open spaces and degraded areas. In the overall assessment, river restoration concepts, although limited by the built environment, produced a minor flood risk index, when compared with a traditional alternative. Keywords: flood risk, risk assessment, river restoration.
The literature on
Conium maculatum biochemistry and toxicology, dispersed in a large number of scientific publications, has been put together in this review.
C. maculatum is a weed known almost ...worldwide by its toxicity to many domestic animals and to human beings. It is an Umbelliferae, characterized by long, hollow stems, reaching up to 2 m height at maturity, producing a large amount of lush foliage during its vegetative growth. Its flowers are white, grouped in umbels formed by numerous umbellules. It produces a large number of seeds that allow the plant to form thick stands in modified soils, sometimes encroaching on cultivated fields, to the extent of impeding the growth of any other vegetation inside the
C. maculatum area of growth. Eight piperidinic alkaloids have been identified in this species. Two of them, γ-coniceine and coniine are generally the most abundant and they account for most of the plant acute and chronic toxicity. These alkaloids are synthesized by the plant from eight acetate units from the metabolic pool, forming a polyketoacid which cyclises through an aminotransferase and forms γ-coniceine as the parent alkaloid via reduction by a NADPH-dependent reductase. The acute toxicity is observed when animals ingest
C. maculatum vegetative and flowering plants and seeds. In a short time the alkaloids produce a neuromuscular blockage conducive to death when the respiratory muscles are affected. The chronic toxicity affects only pregnant animals. When they are poisoned by
C. maculatum during the fetuses organ formation period, the offspring is born with malformations, mainly palatoschisis and multiple congenital contractures (MCC; frequently described as arthrogryposis). Acute toxicity, if not lethal, may resolve in the spontaneous recovery of the affected animals provided further exposure to
C. maculatum is avoided. It has been observed that poisoned animals tend to return to feed on this plant. Chronic toxicity is irreversible and although MCC can be surgically corrected in some cases, most of the malformed animals are lost. Since no specific antidote is available, prevention is the only way to deal with the production loses caused by this weed. Control with herbicides and grazing with less susceptible animals (such as sheep) have been suggested.
C. maculatum alkaloids can be transferred to milk and to fowl muscle tissue through which the former can reach the human food chain. The losses produced by
C. maculatum chronic toxicity may be largely underestimated, at least in some regions, because of the difficulty in associate malformations in offspring with the much earlier maternal poisoning.