Technical and Clinical Outcomes After Transcatheter Edge-to-Edge Repair of Mitral Regurgitation in Male and Female Patients: Is Equality Achieved?

Currently, no clear impact of sex on short- and long-term survival following transcatheter edge-to-edge mitral valve repair (TEER) is evident, although no data are available on postprocedural life expectancy. Our aim was to assess sex-specific differences in outcomes of patients with mitral regurgitation (MR) treated by TEER. Short-term and 5-year outcomes in men and women undergoing TEER between 2011 and 2018 who were included in the large, multicenter, real-world MitraSwiss registry were analyzed. Outcomes were compared stratified by sex and according to MR cause (primary versus secondary). The impact of TEER on postprocedural life expectancy was estimated by relative survival analysis. Among 1142 patients aged 60 to 89 years, 39.8% were women. They were older, with fewer cardiovascular risk factors and lower functional capacity compared with men. Thirty-day mortality was higher in men than in women (3.3% versus 1.1%; odds ratio, 3.16 [95% CI, 1.16-10.7]; P=0.020). Five-year survival was comparable in both sexes (adjusted hazard ratio for 5-year mortality in men, 1.14 [95% CI, 0.90-1.44], P=0.275). Both men and women with either primary or secondary MR showed similar clinical efficacy over time. TEER provided high relative survival estimates among all groups, and fully restored predicted life expectancy in women with primary MR (5-year relative survival estimate, 97.4% [95% CI, 85.5-107.0]). TEER is not associated with increased short-term mortality in women, whereas 5-year outcomes are comparable between sexes. Moreover, TEER completely restored normal life expectancy in women with primary MR. A residual excess mortality persists in secondary MR, independently of sex

Silicon Encapsulated Carbon Nanotubes

A dual stage process of depositing bamboo-like carbon nanotubes (BCNTs) by hot filament chemical vapor deposition (HFCVD) and coating Si using Radio frequency sputtering (RFS) technique. The films were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and electron field emission studies (EFE). SEM results suggest a dense network of homogeneous silicon-coated BCNTs. From the comprehensive analysis of the results provided by these techniques emerges the picture of Si encapsulated BCNTs

The sympathomimetic agonist mirabegron did not lower JAK2-V617F allele burden, but restored nestin-positive cells and reduced reticulin fibrosis in patients with myeloproliferative neoplasms: results of phase II study SAKK 33/14

The β-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of JAK2-V617F positive myeloproliferative neoplasms. We therefore tested the effectiveness of mirabegron, a β-3 sympathomimetic agonist, in a phase II trial including 39 JAK2-V617F positive MPN with a mutant allele burden >20%. Treatment consisted of mirabegron 50 mg daily for 24 weeks. The primary endpoint, reduction of the JAK2-V617F allele burden ≥50%, was not reached in any of the patients. One patient achieved a 25% reduction in JAK2-V617F allele burden by 24 weeks. A small subgroup of patients showed hematological improvement. As a side study, bone marrow biopsies were evaluated in 20 patients.We found an increase in the nestin+ cells from a median of 1.09 (interquartile range 0.38-3.27)/mm2 to 3.95 (interquartile range 1.98-8.79)/mm2 (p<0.0001) and a slight decrease of reticulin fibrosis from a median grade of 1.0 (interquartile range 0-3) to 0.5 (interquartile range 0-2) (p=0.01) between start and end of mirabegron treatment. Despite the fact that the primary endpoint of reducing JAK2-V617F allele burden was not reached, the observed effects on nestin+ MSCs and reticulin fibrosis is encouraging and shows that mirabegron can modify the microenvironment where the JAK2-mutant stem cells are maintained

Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort.

This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response

The FLUKA code: present applications and future developments

The main features of the FLUKA Monte Carlo code, which can deal with transport and interaction of electromagnetic and hadronic particles, are summarised. The physical models embedded in FLUKA are mentioned, as well as examples of benchmarking against experimental data. A short history of the code is provided and the following examples of applications are discussed in detail: prediction of calorimetric performances, atmospheric neutrino flux calculations, dosimetry in atmosphere and radiobiology applications, including hadrontherapy and space radiation protection. Finally a few lines are dedicated to the FLUKA server, from which the code can be downloaded.Comment: talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 8 pages, pd

Comparison of air displacement plethysmography to hydrostatic weighing for estimating total body density in children

BACKGROUND: The purpose of this study was to examine the accuracy of total body density and percent body fat (% fat) using air displacement plethysmography (ADP) and hydrostatic weighing (HW) in children. METHODS: Sixty-six male and female subjects (40 males: 12.4 ± 1.3 yrs, 47.4 ± 14.8 kg, 155.4 ± 11.9 cm, 19.3 ± 4.1 kg/m(2); 26 females: 12.0 ± 1.9 yrs, 41.4 ± 7.7 kg, 152.1 ± 8.9 cm, 17.7 ± 1.7 kg/m(2)) were tested using ADP and HW with ADP always preceding HW. Accuracy, precision, and bias were examined in ADP with HW serving as the criterion method. Lohman's equations that are child specific for age and gender were used to convert body density to % fat. Regression analysis determined the accuracy of ADP and potential bias between ADP and HW using Bland-Altman analysis. RESULTS: For the entire group (Y = 0.835x + 0.171, R(2 )= 0.84, SEE = 0.007 g/cm(3)) and for the males (Y = 0.837x + 0.174, R(2 )= 0.90, SEE = 0.006 g/cm(3)) the regression between total body density by HW and by ADP significantly deviated from the line of identity. However in females, the regression between total body density by HW and ADP did not significantly deviate from the line of identity (Y = 0.750x + 0.258, R(2 )= 0.55, SEE = 0.008 g/cm(3)). The regression between % fat by HW and ADP for the group (Y = 0.84x + 3.81, R(2 )= 0.83, SEE = 3.35 % fat) and for the males (Y = 0.84x + 3.25, R(2 )= 0.90, SEE = 3.00 % fat) significantly deviated from the line of identity. However, in females the regression between % fat by HW and ADP did not significantly deviate from the line of identity (Y = 0.81x + 5.17, R(2 )= 0.56, SEE = 3.80 % fat). Bland-Altman analysis revealed no bias between HW total body density and ADP total body density for the entire group (R = 0.-22; P = 0.08) or for females (R = 0.02; P = 0.92), however bias existed in males (R = -0.37; P ≤ 0.05). Bland-Altman analysis revealed no bias between HW and ADP % fat for the entire group (R = 0.21; P = 0.10) or in females (R = 0.10; P = 0.57), however bias was indicated for males by a significant correlation (R = 0.36; P ≤ 0.05), with ADP underestimating % fat at lower fat values and overestimating at the higher % fat values. CONCLUSION: A significant difference in total body density and % fat was observed between ADP and HW in children 10–15 years old with a potential gender difference being detected. Upon further investigation it was revealed that the study was inadequately powered, thus we recommend that larger studies that are appropriately powered be conducted to better understand this potential gender difference

Parenting Science Gang : radical co-creation of research projects led by parents of young children

Background Parents are increasingly searching online for information supported by research but can find it difficult to identify results relevant to their own experiences. More troublingly, a number of studies indicate that parenting information found online often can be misleading or wrong. The goal of the Parenting Science Gang (PSG) project was to use the power of the Internet to help parents ask questions they wanted to have answered by scientific research and to feel confident in assessing research evidence. Methods By using Facebook to recruit groups and facilitate interactions, PSG was able to engage fully the target public of parents of young children in the radical co-production of scientific studies, while not creating an undue burden on time or restricting participants due to disability, financial status or location. By giving parents true partnership and control of creation of projects, PSG ensured that the chosen questions were ones that were of most relevance and interest to them. Results This paper presents a summary of eight projects, with three in more detail, designed and implemented by PSG Facebook groups in collaboration with experts. Most projects had health related themes, often prompted by dissatisfaction with treatment of parents by health professionals or by feelings of being marginalised by pregnancy and motherhood, as well as by the lack of evidence for their questions and concerns. The PSG approach meant that these frustrations were channelled into actions. All eight of the PSG groups engaged in meaningful interactions with experts and co-produced studies with the groups defining the questions of interest. Conclusions This radically user-led design meant that the PSG staff and the collaborating experts had to live with a high degree of uncertainty. Nevertheless, PSG achieved its goal of academically productive, truly co-produced projects, but as important were the positive effects it had on many of the participants, both parents and experts. At the point of writing this paper, PSG projects have led to outputs including at least eight papers published, in press or in preparation, seven conference presentations, testimony to the Infant Feeding All-Party Parliamentary Group, and with more to come