We investigate the nature of CXOU\,J005440.5-374320 ( a peculiar bright ($ and soft X-ray transient in the spiral galaxy NGC\,300 with a six-hour periodic flux modulation that was detected in a 2014 ...observation. Subsequent observations with and as well as a large observational campaign of NGC\,300 and its sources performed with the Swift Neil Gehrels Observatory showed that this source exhibits recurrent flaring activity: four other outbursts were detected across sim 8 years of monitoring. Using data from the archive and from the and catalogues, we determined that the source is likely associated with a bright blue optical/ultraviolet counterpart. This prompted us to perform follow-up observations with the Southern African Large Telescope in December 2019. With the multi-wavelength information at hand, we discuss several possibilities for the nature of Although none is able to account for the full range of the observed peculiar features, we found that the two most promising scenarios are a stellar-mass compact object in a binary system with a Wolf--Rayet star companion, or the recurrent tidal stripping of a stellar object trapped in a system with an intermediate-mass (sim 1000\,M$_ black hole.
Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. ...Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co‐morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate. The mortality rate ratio standardized to the male Italian population (SMR) was reduced during the periods 1990–1999 and 2000–2007 such that during the latter, death rate overlapped that of the general population (SMR 1990–1999: 1.98 95% CI 1.54–2.51; SMR 2000–2007: 1.08 95% CI 0.83–1.40). Similarly, life expectancy in the whole haemophilic population increased in the same period (71.2 years in 2000–2007 vs. 64.0 in 1990–1999), approaching that of the general male population. While human immunodeficiency virus infection was the main cause of death (45%), 13% of deaths were caused by hepatitis C‐associated complications. The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy.
While primary prophylaxis is a well‐established and recommended method of care delivery for children with severe haemophilia, fewer studies have documented the benefits of secondary prophylaxis ...started in adolescence or adulthood. To evaluate the role of secondary prophylaxis started in adolescent and adult severe haemophiliacs, a retrospective observational cohort study was conducted in 10 Italian Centres that investigated 84 haemophiliacs who had bled frequently and had thus switched from on‐demand to prophylactic treatment during adolescence (n = 30) or adulthood (n = 54). The consumption of clotting factor concentrates, the orthopaedic and radiological scores, quality of life and disease‐related morbidity were compared before and after starting secondary prophylaxis. Prophylaxis reduced the mean annual number of total and joint bleeds (35.8 vs. 4.2 and 32.4 vs. 3.3; P < 0.01) and of days lost from work/school (34.6 vs. 3.0, P < 0.01). A statistically significant reduction in the orthopaedic score was observed during prophylaxis in adolescents, but not in the whole cohort. Patients used more factor concentrates with corresponding higher costs on prophylaxis, but experienced a better quality of life. With respect to on‐demand treatment, higher factor consumption and cost of secondary prophylaxis were balanced by marked clinical benefits and greater well‐being in this cohort of adolescent/adult haemophiliacs.
Although up to 50% of all haemophilic patients followed at haemophilia treatment centres (HTCs) are affected by a mild factor VIII (FVIII) or factor IX (FIX) defect, published data regarding the ...natural history of these disorders are scarce. To fill this lack of information, a retrospective single centre study was conducted. All cases with mild haemophilia (75 A and 7 B) followed at the regional reference HTC of Parma were evaluated. The patients’ median age at diagnosis was 11.5 years and their median age at first bleeding was 5.5 years; 95% of patients had a history of haemorrhagic problems during their life. Twenty‐three percent of patients were infected by HCV, and none by HIV. Genetic analysis was performed in 80 patients (97% haemophilia A and 100% haemophilia B) and 21 different mutations were characterized. Eleven percent of patients had never received treatment, whereas 67% were treated with plasma‐derived or recombinant FVIII/FIX concentrates (4% developed inhibitors). desmopressin (DDAVP) was used in 80% of the haemophilia A patients. The response to DDAVP was closely related to the patients’ genetic profile, as 60% of non‐responders had a mutation in the F8 promoter region. Patients with mild haemophilia may experience a variety of medical problems, sometimes challenging for the physicians, during their lifetime. The HTCs play an important role in the management of these patients, whose diagnosis is often delayed. The HTCs should improve patients’ knowledge and consideration of their disease and encourage them to maintain regular contact with their haemophilia care provider.
Many patients with haemophilia develop inhibitors to factor VIII and require bypassing agents to provide haemostatic cover for limb‐ or life‐threatening bleeding episodes. Due to the reduced risk of ...blood‐borne pathogen transmission with recombinant products, on‐demand recombinant factor VIIa (rFVIIa; NovoSeven®) is the treatment of choice for children with inhibitors. In haemophiliac patients without inhibitors, primary prophylaxis has been clinical practice for several years. This paper summarises 13 case histories of rFVIIa secondary prophylaxis for haemophilia patients with inhibitors. This was a retrospective survey of adult and paediatric severe haemophilia patients with inhibitors treated with rFVIIa from ten European Haemophilia Centres. There was a wide variation in administered rFVIIa dose, from 200–250 μg kg−1 per week to 220 μg kg−1 daily. In many cases, this was lower than the recommended on‐demand dose of rFVIIa. In 12/13 cases, prophylaxis with rFVIIa considerably reduced the number of bleeding episodes compared with previous treatment. Eight/nine patients were satisfied or very satisfied with rFVIIa treatment, and in cases reporting subjective quality of life (QoL), all were improved, much improved, or significantly improved. In haemophilia patients with inhibitors, prophylaxis with rFVIIa is highly effective in reducing the number of bleeding episodes and results in good patient compliance and improved QoL. Randomised controlled trials are needed to confirm these findings. Results of a recently completed clinical trial on secondary prophylaxis with rFVIIa in frequently bleeding haemophilia patients with inhibitors are expected in late 2006.
The term now cast in hydro meteorology reflects the need for timely and accurate predictions of risky environmental situations, which are related to the development of severe meteorological events at ...short time scales. The objective of this paper is to apply a fully neural-network approach to the rainfall field now casting from infrared (IR) and microwave (MW) passive-sensor imagery aboard, respectively, geostationary Earth orbit (GEO) and low Earth orbit (LEO) satellites. The multisatellite space-time prediction procedure, which is named Neural Combined Algorithm for Storm Tracking (NeuCAST), consists of two consecutive steps. First, the IR radiance field measured from a geostationary satellite radiometer (e.g., Meteosat) is projected ahead in time (e.g., 30 min); second, the projected radiance field is used in estimating the rainfall field by means of an MW-IR combined rain retrieval algorithm exploiting GEO-LEO observations. The NeuCAST methodology is extensively illustrated and discussed in this paper. Its accuracy is quantified by means of quantitative error indexes, which are evaluated on selected case studies of rainfall events in Southern Europe in 2003 and 2005.
Summary
The low‐density lipoprotein receptor‐related protein 1 (LRP1) is an ubiquitously expressed endocytic receptor that, among its several functions, is involved in the catabolism of coagulation ...factor VIII (FVIII) and in the regulation of its plasma concentrations. Although LRP1/CD91 polymorphisms have been associated with increased FVIII levels and a consequent thrombotic risk, no data are available on LRP1/CD91 expression in patients with inherited FVIII deficiency. With the aim of elucidating this issue, 45 consecutive patients with haemophilia A (HA) (18 severe, 5 moderate and 22 mild HA) were enrolled in this cross‐sectional, single‐centre survey. The LRP1/CD91 mean fluorescence intensity (MFI) in monocytes from HA patients was significantly higher than that detected in 90 healthy blood donors (105 vs. 67, P < 0.001). This over‐expression was independent of hepatitis C virus infection status and varied according to the severity of the haemophilia, being higher in patients with more severe FVIII deficiency. In conclusion, our study documents for the first time that LRP1/CD91 is over‐expressed on monocytes from HA patients, with the intensity of expression varying according to the severity of the FVIII deficiency. Further studies are needed to assess the clinical implications of these findings.
Haemophilia A (HA) is an X‐linked recessive bleeding disorder caused by a lack or decrease of coagulation factor VIII activity. The molecular diagnosis of HA is challenging and a variety of different ...mutations have been identified throughout the F8 gene. Our aim was to detect the causative mutation in 266 HA patients from Emilia‐Romagna region (Italy) and in all suspected carriers. Molecular analysis of F8 in 201 HA patients (152 index cases) was performed with a combination of several indirect and direct molecular approaches, such as long distance polymerase chain reaction, multiplex ligation‐dependent probe amplification, denaturing high performance liquid chromatography and direct sequencing. The analysis revealed 78 different mutations, 23 of which were novel, not having been reported in national or international databases. The detection rate was 100%, 86% and 89% in patients with severe, moderate and mild HA, respectively. The information provided by this registry will be helpful for monitoring the treatment of HA patients in Emilia‐Romagna and also for reliable genetic counselling of affected families in the future.
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