A model learning based testing approach for kernel P systems

YesKernel P systems have been introduced as a unifying formalism allowing to specify, simulate and analyse various problems. Several applications of this model have been considered and a powerful tool built in order to support their development and analysis. Testing represents an important aspect of any system analysis and correctness. In this paper we introduce for the first time a bounded test generation approach for kernel P systems by considering bounded input sequences. A learning algorithm for kernel P systems is based on learning X-machine models that are equivalent to these systems for sequences of steps up to a certain limit, ℓ. The Lℓ learning algorithm is used. The testing approach is then devised from the inferred X-machines. The method is applied to a case study illustrating the key parts of the approach.This research was supported by the European Regional Development Fund, Competitiveness Operational Program 2014-2020 through project IDBC (code SMIS 2014+: 121512). Raluca Lefticaru, Savas Konur and Marian Gheorghe have been partially supported by the Royal Society grant IES╲R3╲213176, 2022-2024. The work of Savas Konur is also supported by EPSRC (EP/R043787/1)

Towards an Integrated Approach for Model Simulation, Property Extraction and Veri cation of P Systems

This paper presents an integrated approach for model simulation, property extraction and formal veri cation of P systems, illustrated on a tissue P system with active membranes solving the 3-colouring problem. The paper focuses on this problem and reports the invariants and the properties extracted and veri ed using a series of tools (Daikon, MeCoSim, Maple, Spin, ProB) and languages (P{Lingua, Promela, Event-B). Appropriate tools and integration plugins, which facilitate and even automate the steps involved in the aforementioned approach, have also been developed. The case study chosen is complex (it involves an exponential growth of the number of states through the use of membrane division rules) and the properties obtained are non-trivial.Ministerio de Ciencia e Innovación TIN2009–13192Junta de Andalucía P08–TIC–0420

Leczenie akromegalii w Rumunii. Jak blisko jesteśmy uzyskania kontroli nad chorobą?

Introduction: In Romania, no nationwide data for acromegaly treatment and control rate are available. Our objective was to assess the acromegaly control rate in a tertiary referral centre, which covers an important part of Romanian territory and population of patients with acromegaly. Materials and methods: We reviewed the records of all 164 patients (49 males and 115 females; median age 55 [47, 63.5] years) with newly or previously diagnosed acromegaly, who have been assessed at least once in our tertiary referral centre between January 1, 2012 and March 31, 2016. This sample represents 13.6% of the total expected 1200 Romanian patients with acromegaly and covers 82.9% of the counties in Romania. Control of acromegaly was defined as a random serum growth hormone (GH) < 1 ng/mL and an age-normalised serum insulin-like growth factor-I (IGF-I) value. The GH and IGF-I values used for calculation of the control rate were those at the last evaluation. The same assays for GH and IGF-I measurement were used in all patients. Results: There were 147 treated and 17 untreated patients. Of the 147 patients assessed after therapy, 137 (93.2%) had pituitary surgery, 116 (78.9%) were on medical treatment at the last evaluation, and 67 (45.5%) had radiotherapy. Seventy-one (48.3%) had a random GH < 1 ng/mL, 54 (36.7%) had a normalised, age-adjusted IGF-I, and 42 (28.6%) had both normal random serum GH and IGF-I. Conclusions: In Romania, acromegaly benefits from the whole spectrum of therapeutic interventions. However, the control rate remains disappointing.Wstęp: W Rumunii nie są dostępne ogólnokrajowe dane dotyczące leczenia akromegalii ani wskaźnika kontroli choroby. Badanie przeprowadzono w celu oceny wskaźnika kontroli akromegalii w ośrodku referencyjnym trzeciego stopnia, który obejmuje opieką zdrowotną znaczną część obszaru Rumunii i populacji pacjentów z akromegalią. Materiał i metody: Autorzy dokonali przeglądu danych medycznych wszystkich 164 chorych [49 mężczyzn i 115 kobiet; mediana wieku 55 lat (47; 63,5)] z noworozpoznaną lub wcześniej zdiagnozowaną akromegalią, których przynajmniej jednokrotnie zbadano w ośrodku referencyjnym trzeciego stopnia (miejsce pracy autorów) w okresie od 1 stycznia 2012 roku do 31 marca 2016 roku. Ta próba stanowiła 13,6% całej rumuńskiej populacji chorych na akromegalię szacowaną na 1200 osób i reprezentowała 82,9% okręgów administracyjnych w Rumunii. Kontrolę akromegalii definiowano jako stężenie przygodne hormonu wzrostu (growth hormone, GH) w surowicy wynoszące poniżej 1 ng/ml oraz normalizacja odpowiednio do wieku stężenia insulinopodobnego czynnika wzrostu 1 (insulin-like growth factor-1, IGF-1) w surowicy. Do obliczenia wskaźnika kontroli choroby stosowano wartości GH i IGF-1 z ostatnich pomiarów. U wszystkich pacjentów używano tych samych testów do pomiarów GH i IGF-1. Wyniki: Badanie obejmowało 147 chorych poddanych leczeniu i 17 chorych nieleczonych. Spośród 147 chorych ocenianych po terapii, u 137 (93,2%) zastosowano leczenie chirurgiczne, 116 (78,9%) w momencie ostatniej wizyty kontrolnej stosowało leczenie farmakologiczne, a 67 (45,5%) poddano radioterapii. U 71 chorych (48,3%) przygodne stężenie GH w surowicy wynosiło poniżej 1 ng/ml, u 54 (36,7%) uzyskano normalizację stężenia IGF-1 skorygowanego względem wieku, a u 42 chorych (28,6%) uzyskano normalizację obu parametrów — GH i IGF-1. Wnioski: W Rumunii u chorych na akromegalię stosuje się szerokie spektrum interwencji terapeutycznych, jednak wskaźnik kontroli choroby nadal pozostaje niezadawalający

Epidemic dispersion of HIV and HCV in a population of co-infected Romanian injecting drug users

Co-infections with HIV and HCV are very frequent among people who inject drugs (PWID). However, very few studies comparatively reconstructed the transmission patterns of both viruses in the same population. We have recruited 117 co-infected PWID during a recent HIV outbreak in Romania. Phylogenetic analyses were performed on HIV and HCV sequences in order to characterize and compare transmission dynamics of the two viruses. Three large HIV clusters (2 subtype F1 and one CRF14_BG) and thirteen smaller HCV transmission networks (genotypes 1a, 1b, 3a, 4a and 4d) were identified. Eighty (65%) patients were both in HIV and HCV transmission chains and 70 of those shared the same HIV and HCV cluster with at least one other patient. Molecular clock analysis indicated that all identified HIV clusters originated around 2006, while the origin of the different HCV clusters ranged between 1980 (genotype 1b) and 2011 (genotypes 3a and 4d). HCV infection preceded HIV infection in 80.3% of cases. Coincidental transmission of HIV and HCV was estimated to be rather low (19.65%) and associated with an outbreak among PWID during detention in the same penitentiary. This study has reconstructed and compared the dispersion of these two viruses in a PWID population. © 2017 Paraschiv et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

High mortality risk among women with acromegaly still persists

IntroductionThe mortality ratio in patients with acromegaly has improved over the last few decades. We aimed to determine the mortality rate and correlated factors in patients with acromegaly before and after the introduction of national protocols for treatment. In addition, we determined whether there are sex-related differences in mortality of patients with acromegaly.MethodsThis observational retrospective study included 399 consecutive patients with acromegaly between January 2001–December 2022. Paraclinical data included random growth hormone (GH) and insulin-like growth factor-I (IGF1) levels, maximal pituitary tumor diameter at diagnosis, first visit, and last evaluation. Standardized mortality ratio (SMR) was calculated by dividing the observed and expected mortality rates. Cox regression analysis revealed the independent factors associated with mortality.ResultsAt the last visit, 31.07% (124) of patients were cured, 22.05% (88) had controlled acromegaly with medication, and 45.31% (181) had not controlled acromegaly. During follow-up (13.03 ± 5.65 years, 5216.62 person-years), 89 patients died (0.017%), resulting in an SMR of 1.18 [95% CI 0.95–1.45]. The independent factors associated with mortality were the last IGF1 level/last random GH level, absence of surgery, gonadotropin deficiency, and age. Patients with normal IGF1 after treatment showed an SMR of 0.71, whereas patients with IGF1 ratio > 1 showed SMR=1.51. Patients diagnosed between 1975–2007 and 2008–2022 had SMR = 1.25 [95% CI 0.97–1.58] and SMR = 1.09 [95% CI 0.68–1.65], respectively. In females with acromegaly, SMR was 1.63 [95% CI 1.24–2.11]; 1.76 [95% CI 1.30–2.34] in women diagnosed before 2008 and 1.33 [95% CI 0.69–2.33] in those diagnosed after 2008. Males with acromegaly had a mortality ratio similar to males from the general population (SMR = 0.99, [95% CI 0.66–1.41]).ConclusionPatients diagnosed with acromegaly in the last 15 years had lower mortality rates than those diagnosed before 2008, due to the availability of new medications, primarily somatostatin receptor analogs and to a higher proportion of patients undergoing surgery. Females still have a high mortality ratio owing to older age at diagnosis and higher risk of metabolic complications. Therefore, efforts should be made for early diagnosis of acromegaly in women

Improvement of acromegaly control with multimodal therapy in Romania

Introduction: In Romania, there is no acromegaly national register and there are no nationwide data available. However, some studies have reported the control rates in the country’s main referral centres. Our aim was to assess the overall control rate in our tertiary referral centre. Also, we assessed the control rate in the last three years, and we compared the results with our previous reports. Material and methods: We reviewed the charts of 186 patients with acromegaly assessed in our department between January 1st, 2012 and May 31st, 2019. We also compared the control rates for patients treated between April 1st, 2016 and May 31st, 2019 with historical controls (assessed between January 1st, 2012 and March 31st, 2016). Results: Primary analysis: There were 19 untreated and 167 treated patients, mean age 52.46 years, surgery being the most commonly used treatment. The surgical cure rate was 14.8%, and disease control with medical treatment was 35.3%. Secondary analysis: In the first group there were 45 patients, surgery also being the most commonly used treatment. The surgical cure rate was 26.9%, and disease control was 30.4%. In the second group (historical controls) there were 42 patients, surgery being the most commonly used treatment. The surgical cure rate was 9.7%, and disease control with medical treatment was 15.4%. Random GH and IGF-1 after surgery were lower in the first group (p < 0.05) Conclusions: Changes in the Romanian protocol and highly specialised pituitary centres has improved the cure rate and disease control in patients with acromegaly.

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations