Prevalence of low antithrombin levels in preeclamptic women and perinatal outcome

Objective. The aim of this study is to evaluate the prevalence of low antithrombin levels in our population in order to assess an intervention trial feasibility. Methods. This is a retrospective study. A database was created by using queries to find out medical records of patients requiring hospitalization for preeclampsia or gestational hypertension or superimposed preeclampsia to chronic hypertension at Modena University Hospital between June 2015 and July 2019. Results. We screened 11845 deliveries. Overall, 221 (1.9%) cases of preeclampsia were identified. Antithrombin level was available for 201 women, thus included in the analysis. Median antithrombin value was 87% (IQ range: 77-98). The prevalence of low antithrombin levels was 9%. Antithrombin < 80% was found in 21% of the subjects. The remnant showed normal values. Median antithrombin was significantly lower in severe respect with mild preeclampsia (83% ± 14 vs 89% ± 14, p = 0.003). The rate of small for gestational age was significantly higher in low antithrombin levels group (44.4% vs 22.4%, p = 0.042). Considering mean values, antithrombin levels were also significantly lower in case of small for gestational age (84% ± 14 vs 89% ± 14; p = 0.040). Conclusions. In our population, low antithrombin levels (1 in 10 patients) were associated with severity of preeclampsia, namely with small for gestational age babies. Data suggest this subpopulation as a better target for trials assessing the efficacy of antithrombin supplementation

A Theory of Sampling for Continuous-time Metric Temporal Logic

This paper revisits the classical notion of sampling in the setting of real-time temporal logics for the modeling and analysis of systems. The relationship between the satisfiability of Metric Temporal Logic (MTL) formulas over continuous-time models and over discrete-time models is studied. It is shown to what extent discrete-time sequences obtained by sampling continuous-time signals capture the semantics of MTL formulas over the two time domains. The main results apply to "flat" formulas that do not nest temporal operators and can be applied to the problem of reducing the verification problem for MTL over continuous-time models to the same problem over discrete-time, resulting in an automated partial practically-efficient discretization technique.Comment: Revised version, 43 pages

A computational search for box C/D snoRNA genes in the Drosophila melanogaster genome

Abstract Motivation: In eukaryotes, the family of non-coding RNA genes includes a number of genes encoding small nucleolar RNAs (mainly C/D and H/ACA snoRNAs), which act as guides in the maturation or post-transcriptional modifications of target RNA molecules. Since in Drosophila melanogaster (Dm) only few examples of snoRNAs have been identified so far by cDNA libraries screening, integration of the molecular data with in silico identification of these types of genes could throw light on their organization in the Dm genome. Results: We have performed a computational screening of the Dm genome for C/D snoRNA genes, followed by experimental validation of the putative candidates. Few of the 26 confirmed snoRNAs had been recognized by cDNA library analysis. Organization of the Dm genome was also found to be more variegated than previously suspected, with snoRNA genes nested in both the introns and exons of protein-coding genes. This finding suggests that the presence of additional mechanisms of snoRNA biogenesis based on the alternative production of overlapping mRNA/snoRNA molecules. Availability: Additional information is available at http://www.bioinformatica.unito.it/bioinformatics/snoRNA

Appropriateness of frequent use of emergency departments: A retrospective analysis in Rome, Italy

Background: Frequent users (FUs) are patients who repeatedly and inappropriately visit the emergency department (ED) for low-grade symptoms that could be treated outside the hospital setting. This study aimed to investigate the phenomenon of the FU in Rome by profiling such users and analyzing ED attendance by FUs. Methods: The analysis was carried out for attendance in 2021 at 15 EDs in the Local Health Authority Roma 1 geographical area. A digital app collected data, including information on the following variables: number of attendance, demographic characteristics, emergency medical service (EMS) usage, triage code, and appropriateness of attendance. COVID-19 diagnosis was also studied to analyze any possible influence on ED attendance. Differences between FUs and non-FUs were investigated statistically by t-test and chi-square test. Univariate analysis and multivariable logistic regression were performed to analyze the associated factors. Results: A total of 122,762 ED attendance and 89,036 users were registered. The FU category represented 2.9% of all users, comprising 11.9% of total ED attendance. There was a three times higher frequency of non-urgent codes in attendance of FU patients (FU: 9.7%; non-FU: 3.2%). FUs were slightly more likely to have used the EMS (13.6% vs. 11.4%) and had a lower frequency of appropriate ED attendance (23.8% vs. 27.0%). Multivariate logistic analysis confirmed a significant effect of triage code, gender, age, EMS usage, and COVID-19 diagnosis for the appropriateness of attendance. The results were statistically significant (p < 0.001). Conclusion: The FU profile describes mostly non-urgent and inappropriate attendance at the ED, including during the COVID-19 pandemic. This study represents an important tool for strengthening preventive policies outside the hospital setting. The Italian National Recovery and Resilience Plan represents an excellent opportunity for the development of new strategies to mitigate the phenomenon of FUs

Clinical and pathology characterization of small nerve fiber neuro(no)pathy in cerebellar ataxia with neuropathy and vestibular areflexia syndrome

Background and purpose: Biallelic mutation/expansion of the gene RFC1 has been described in association with a spectrum of manifestations ranging from isolated sensory neuro(no)pathy to a complex presentation as cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Our aim was to define the frequency and characteristics of small fiber neuropathy (SFN) in RFC1 disease at different stages. Methods: RFC1 cases were screened for SFN using the Neuropathic Pain Symptom Inventory and Composite Autonomic Symptom Score 31 questionnaires. Clinical data were retrospectively collected. If available, lower limb skin biopsy samples were evaluated for somatic epidermal and autonomic subepidermal structure innervation and compared to healthy controls (HCs). Results: Forty patients, median age at onset 54 years (interquartile range [IQR] 49–61) and disease duration 10 years (IQR 6–16), were enrolled. Mild-to-moderate positive symptoms (median Neuropathic Pain Symptom Inventory score 12.1/50, IQR 5.5–22.3) and relevant autonomic disturbances (median Composite Autonomic Symptom Score 31 37.0/100, IQR 17.7–44.3) were frequently reported and showed scarce correlation with disease duration. A non-length-dependent impairment in nociception was evident in both clinical and paraclinical investigations. An extreme somatic denervation was observed in all patients at both proximal (fibers/mm, RFC1 cases 0.0 vs. HCs 20.5, p < 0.0001) and distal sites (fibers/mm, RFC1 cases 0.0 vs. HCs 13.1, p < 0.0001); instead only a slight decrease was observed in cholinergic and adrenergic innervation of autonomic structures. Conclusions: RFC1 disease is characterized by a severe and widespread somatic SFN. Skin denervation may potentially represent the earliest feature and drive towards the suspicion of this disorder

Inferring loop invariants by mutation, dynamic analysis, and static checking

Verifiers that can prove programs correct against their full functional specification require, for programs with loops, additional annotations in the form of loop invariants - properties that hold for every iteration of a loop. We show that significant loop invariant candidates can be generated by systematically mutating postconditions; then, dynamic checking (based on automatically generated tests) weeds out invalid candidates, and static checking selects provably valid ones. We present a framework that automatically applies these techniques to support a program prover, paving the way for fully automatic verification without manually written loop invariants: Applied to 28 methods (including 39 different loops) from various Java.util classes (occasionally modified to avoid using Java features not fully supported by the static checker), our DYNAMATE prototype automatically discharged 97 percent of all proof obligations, resulting in automatic complete correctness proofs of 25 out of the 28 methods - outperforming several state-of-the-art tools for fully automatic verification

Establishing kidney transplantation in a low-income country: a case in Tanzania

Background Sub-Saharan African countries, including Tanzania, have a high burden of chronic kidney diseases (CKDs) and limited capacity for the provision of services. Tanzania and other countries in the region have made signifcant improvements in the provision of services for patients with CKD, including hemodialysis. Few countries are ofering kidney transplantation services, which is the defnitive treatment for patients with CKD and kidney failure. This study was conducted to review the steps taken by Muhimbili National Hospital (MNH) to establish a kidney transplantation service in Tanzania. Methods This study was based on the review of the activities that were undertaken to establish kidney transplantation services at Muhimbili National Hospital in Dar es Salaam, Tanzania. It was conducted by reviewing key documents developed for kidney transplantation and interviewing key personnel who were involved in the process. Results Kidney transplantation services at MNH were established in November 2017; several steps were taken in the preparatory phase including training of personnel, infrastructural modifcations, and procurement of equipment and supplies. Capacity building was achieved through international collaboration with several international and local institutions, including three Hospitals in India. The transplant team, which included nephrologists, urologists, anesthesiologists, radiologists, nurses, laboratory technicians, a transplant coordinator, and a lawyer, underwent shortterm training at BLK Hospital in India. Initial transplant procedures were carried out with support from visiting personnel from BLK, Sakra, and Seifee hospitals. In total, 72 transplant surgeries were conducted, of which 39 (54.2%) were performed with visiting teams and 31 (45.8%) by the local team independently. Of the initial 39 recipients, 56.4% were males and 43.5% were aged above 46 years. About half of the donors were brothers/sisters, and 43.5% had human leukocytic antigen haplomatch. Induction immunosuppression included basiliximab in the majority (64.1%) of recipients, and all recipients received prednisolone, tacrolimus, and mycophenolate mofetil/myfortic. Conclusions Establishing kidney transplantation in lower-income countries, such as Tanzania, is feasible; however, it requires dedicated eforts. Collaboration with local and international institutions provided an enabling environment for the transfer of skills and access to necessary supportive services

The SUCCESSO-TERRA project: A lesson of sustainability from the terramare culture, middle bronze age of the po plain (Northern Italy)

This backstory article deals with the SUCCESSO-TERRA Project (2017–2020), an interdisciplinary research program aiming at reconstructing the land-use transformations that occurred during the development of the Terramare culture in the southern-central Po Plain of Northern Italy. Topics include climate-environment changes, human impact and exploitation of natural resources that are interconnected topics in human ecology and environmental sciences. These topics can only be understood in a long-term perspective integrating archaeology, geology, botany and other sciences. The text includes the theoretical basis, the research strategy and the main methodological approaches given by geoarchaeology and palynology, the two research sides constituting the partnership of the project

A timeband framework for modelling real-time systems

Complex real-time systems must integrate physical processes with digital control, human operation and organisational structures. New scientific foundations are required for specifying, designing and implementing these systems. One key challenge is to cope with the wide range of time scales and dynamics inherent in such systems. To exploit the unique properties of time, with the aim of producing more dependable computer-based systems, it is desirable to explicitly identify distinct time bands in which the system is situated. Such a framework enables the temporal properties and associated dynamic behaviour of existing systems to be described and the requirements for new or modified systems to be specified. A system model based on a finite set of distinct time bands is motivated and developed in this paper

Exploiting the tunability of stimulated emission depletion microscopy for super-resolution imaging of nuclear structures

Imaging of nuclear structures within intact eukaryotic nuclei is imperative to understand the effect of chromatin folding on genome function. Recent developments of super-resolution fluorescence microscopy techniques combine high specificity, sensitivity, and less-invasive sample preparation procedures with the sub-diffraction spatial resolution required to image chromatin at the nanoscale. Here, we present a method to enhance the spatial resolution of a stimulated-emission depletion (STED) microscope based only on the modulation of the STED intensity during the acquisition of a STED image. This modulation induces spatially encoded variations of the fluorescence emission that can be visualized in the phasor plot and used to improve and quantify the effective spatial resolution of the STED image. We show that the method can be used to remove direct excitation by the STED beam and perform dual color imaging. We apply this method to the visualization of transcription and replication foci within intact nuclei of eukaryotic cells