Familial Sneddon's syndrome

A syndrome associating Livedo Reticularis (LR) with Cerebrovascular disease (CVD) was described, in 1965, by Sneddon. It occurs sporadically, but a few familial cases of Sneddon's Syndrome (SS) have been reported, like these 3 cases that represent one of the largest number among siblings. We studied three male brothers, aged 28, 37 and 42 years, with CVD (ischaemic stroke in 2 patients and cerebral haemorrhages in the third) and their sister with no CVD. All patients presented with long lasting Livedo Reticularis, extending beyond the lower limbs. Skin biopsy on the centre of the reticular pattern showed, only in the second patient, partial endothelium detachment in dermo-hypodermic blood vessels. The males also had accesses of Livedoid Vasculitis (LV), in which a skin biopsy showed obliteration of several upper dermal vessels with hialin thrombi and a very scarce inflammatory infiltrate. Complementary studies, with an extensive investigation on pro-coagulation/pro-thrombotic features including antiphospholipid antibodies, were repeatedly negative. Their non-consanguineous parents were not affected, but among these kindred of 9 individuals, apart from the 4 patients reported above, LR and LV were present in two other brothers and also in an aunt and uncle, suggesting autosomal dominant pattern of inheritance, with incomplete penetrance. The relationship between Sneddon's Syndrome and Antiphospholipid Antibody Syndrome is controversial. The present cases, having repeatedly negative antiphospholipid antibodies, support the classification of Sneddon's Syndrome as an independent nosological entity

The role experience of advanced practice nurses in oncology: An interpretative phenomenological study.

Aim(s): To understand the experiences of advanced practice nurses working in cancer care. Design: Phenomenological qualitative study. Methods: Three focus groups were held to collect qualitative data. Participants were recruited through theoretical non-probabilistic sampling of maximum variation, based on 12 profiles. Data saturation was achieved with a final sample of 21 oncology advanced practice nurses who were performing advanced clinical practice roles in the four centers from December 2021 to March 2022. An interpretative phenomenological analysis was performed following Guba and Lincoln's criteria of trustworthiness. The centers' ethics committee approved the study, and all participants gave written informed consent. Data analysis was undertaken with NVivo 12 software. Results: Three broad themes emerged from the data analysis: the role performed, facilitators and barriers in the development of the role and nurses' lived experience of the role. Conclusion: Advanced practice nurses are aware that they do not perform their role to its full potential, and they describe different facilitators and barriers. Despite the difficulties, they present a positive attitude as well as a capacity for leadership, which has allowed them to consolidate the advanced practice nursing role in unfavourable environments. Implications for the profession: These results will enable institutions to establish strategies at different levels in the implementation and development of advanced practice nursing roles. Reporting method: Reporting complied with COREQ criteria for qualitative research. Patient or public contributions: No patient or public contribution

CD31 signals confer immune privilege to the vascular endothelium

This work was supported by British Heart Foundation Grant FS/11/64/ 2894

An efficient semiparametric maxima estimator of the extremal index

The extremal index $\theta$, a measure of the degree of local dependence in the extremes of a stationary process, plays an important role in extreme value analyses. We estimate $\theta$ semiparametrically, using the relationship between the distribution of block maxima and the marginal distribution of a process to define a semiparametric model. We show that these semiparametric estimators are simpler and substantially more efficient than their parametric counterparts. We seek to improve efficiency further using maxima over sliding blocks. A simulation study shows that the semiparametric estimators are competitive with the leading estimators. An application to sea-surge heights combines inferences about $\theta$ with a standard extreme value analysis of block maxima to estimate marginal quantiles.Comment: 17 pages, 7 figures. Minor edits made to version 1 prior to journal publication. The final publication is available at Springer via http://dx.doi.org/10.1007/s10687-015-0221-

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

<p>Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.</p> <p>Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.</p> <p>Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.</p> <p>Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.</p&gt

Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

Background Acute promyelocytic leukemia is a subtype of acute myeloid leukemia characterized by the t(15;17). The incidence and prognostic significance of additional chromosomal abnormalities in acute promyelocytic leukemia is still a controversial matter. Design and Methods Based on cytogenetic data available for 495 patients with acute promyelocytic leukemia enrolled in two consecutive PETHEMA trials (LPA96 and LPA99), we analyzed the incidence, characteristics, and outcome of patients with acute promyelocytic leukemia with and without additional chromosomal abnormalities who had been treated with all-trans retinoic acid plus anthracycline monochemotherapy for induction and consolidation. Results Additional chromosomal abnormalities were observed in 140 patients (28%). Trisomy 8 was the most frequent abnormality (36%), followed by abn(7q) (5%). Patients with additional chromosomal abnormalities more frequently had coagulopathy (P=0.03), lower platelet counts (P=0.02), and higher relapse-risk scores (P=0.02) than their counterparts without additional abnormalities. No significant association with FLT3/ITD or other clinicopathological characteristics was demonstrated. Patients with and without additional chromosomal abnormalities had similar complete remission rates (90% and 91%, respectively). Univariate analysis showed that additional chromosomal abnormalities were associated with a lower relapse-free survival in the LPA99 trial (P=0.04), but not in the LPA96 trial. However, neither additional chromosomal abnormalities overall nor any specific abnormality was identified as an independent risk factor for relapse in multivariate analysis. Conclusions The lack of independent prognostic value of additional chromosomal abnormalities in acute promyelocytic leukemia does not support the use of alternative therapeutic strategies when such abnormalities are found

Nucleon Charge and Magnetization Densities from Sachs Form Factors

Relativistic prescriptions relating Sachs form factors to nucleon charge and magnetization densities are used to fit recent data for both the proton and the neutron. The analysis uses expansions in complete radial bases to minimize model dependence and to estimate the uncertainties in radial densities due to limitation of the range of momentum transfer. We find that the charge distribution for the proton is significantly broad than its magnetization density and that the magnetization density is slightly broader for the neutron than the proton. The neutron charge form factor is consistent with the Galster parametrization over the available range of Q^2, but relativistic inversion produces a softer radial density. Discrete ambiguities in the inversion method are analyzed in detail. The method of Mitra and Kumari ensures compatibility with pQCD and is most useful for extrapolating form factors to large Q^2.Comment: To appear in Phys. Rev. C. Two new figures and accompanying text have been added and several discussions have been clarified with no significant changes to the conclusions. Now contains 47 pages including 21 figures and 2 table

Mobile Manipulation Hackathon: Moving into Real World Applications

The Mobile Manipulation Hackathon was held in late 2018 during the IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS) to showcase the latest applications of wheeled robotic manipulators. The challenge had an open format, where teams developed an application using simulation tools and integrated it into a robotic platform. This article presents the competition and analyzes the results, with information gathered during the event and from a survey circulated among the finalist teams. We provide an overview of the mobile manipulation field, identify key areas required for further development to facilitate the implementation of mobile manipulators in real applications, and discuss ideas about how to structure future hackathon-style competitions to enhance their impact on the scientific and industrial communities.Peer ReviewedPostprint (published version

Istodobno spektrofotometrijsko određivanje losartan kalija, amlodipin besilata i hidroklorotiazida u farmaceutskim pripravcima kemometrijskom metodom

In the present work, four different spectrophotometric methods for simultaneous estimation of losartan potassium, amlodipine besilate and hydrochlorothiazide in raw materials and in formulations are described. Overlapped data was quantitatively resolved by using chemometric methods, classical least squares (CLS), multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS). Calibrations were constructed using the absorption data matrix corresponding to the concentration data matrix, with measurements in the range of 230.5350.4 nm (∆λ = 0.1 nm) in their zero order spectra. The linearity range was found to be 840, 15 and 315 μg ml1 for losartan potassium, amlodipine besilate and hydrochlorothiazide, respectively. The validity of the proposed methods was successfully assessed for analyses of drugs in the various prepared physical mixtures and in tablet formulations.U radu su opisane četiri spektrofotometrijske metode za istodobno određivanje losartan kalija, amlodipin besilata i hidroklorotiazida u sirovinama i farmaceutskim pripravcima. Podaci koji su se preklapali kvantitativno su razlučeni kemometrijskim metodama, klasičnom metodom najmanjih kvadrata (CLS), multiplom linearnom regresijom (MLR), regresijom glavnih komponenata (PCR) te metodom parcijalnih najmanjih kvadrata (PLS). Kalibracije su provedene koristeći podatke o ovisnosti apsorpcije o koncentracijama, mjereći spektre nultog reda u rasponu 230,5350,4 nm (∆λ = 0,1 nm). Linearnost za losartan kalij bila je 840, za amlodipin besilat 15, a za hidroklorotiazid 315 μg ml1. Valjanost predloženih metoda uspješno je potvrđena analizom navedenih lijekova u različitim pripremljenim smjesama i tabletama