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Rates of permanent pacemaker (PPM) implantation following transcatheter aortic valve implantation (TAVI) are higher than following surgery and are dependent on patient factors and valve type. There is an increasing trend towards pre-emptive PPM insertion in patients with significant conduction disease prior to TAVI. We report results from the British Cardiovascular Intervention Society (BCIS) on pre- and post-procedural PPM implantation in the TAVI population. All centres in the United Kingdom performing TAVI are required to submit data on all TAVI procedures to the National database which are then reported annually. During 2015, there were 2373 TAVI procedures in the UK. 22.4% of TAVI patients had a PPM implanted either pre-procedure (including the distant past), or during the in-hospital procedural episode. Of these, 7.9% were pre-procedure and 14.5% post-procedure. Overall PPM rates were Edwards Sapien (13.5%), Medtronic CoreValve (28.2%) and Boston Lotus (42.1%; p less then 0.01). compound library chemical Pre-procedure pacing rates were Edwards Sapien (6.0%), Medtronic CoreValve (9.1%) and Boston Lotus (12.3%; p less then 0.01). Pre-procedural pacing rates for the Boston Lotus valve have risen year-on-year from 5.8% (2013) to 8.6% (2014) to 12.3% (2015). The UK TAVI Registry demonstrates a pre-procedural permanent pacing bias amongst patients receiving transcatheter valves with higher post-procedure pacing rates. Pre-emptive permanent pacing is likely to be responsible for this difference.The synthesis and characterization of two half-sandwich complexes of Ru(II) and Ir(III) with thiabendazole as ancillary ligand and their DNA binding ability were investigated using experimental and computational methods. 1H NMR and acid-base studies have shown that aquo-complexes are the reactive species. Kinetic studies show that both complexes bind covalently to DNA through the metal site and non covalently through the ancillary ligand. Thermal stability studies, viscosity, circular dichroism measurements and quantum chemical calculations have shown that the covalent binding causes breaking of the H-bonding between base pairs, bringing about DNA denaturation and compaction. Additionally, molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations shed light into the binding features of the Ru(II) and Ir(III) complexes and their respective enantiomers toward double-helical DNA, highlighting the important role played by the NˆN ancillary ligand once the complexes are covalently linked to DNA. Moreover, metal quantification in the nucleus of SW480 colon adenocarcinoma cells were carried out by inductively coupled plasma-mass spectrometry (ICP-MS), both complexes are more internalized than cisplatin after 4 h of exposition. However, in spite of the dramatic changes in the helicity of the DNA secondary structure induced by these complexes and their nuclear localization, antiproliferative studies have revealed that both, Ru(II) and Ir(III) complexes, cannot be considered cytotoxic. This unexpected behavior can be justified by the fast formation of aquo-complexes, which may react with components of the cell culture medium or the cytoplasm compartment in such a way that they may become deactivated before reaching DNA.
Little is known about the use of trastuzumab or trastuzumab + lapatinib in older patients. We have performed a sub-analysis of the Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation (ALTTO) trial focused on toxicity and treatment completion of both regimens in older patients (≥ 65years old) METHODS The ALTTO trial randomised 8381 patients with early HER2-positive BC in 4 arms. Eligible patients for this study were those having received at least one dose of assigned treatment in either the trastuzumab or trastuzumab + lapatinib arms. Treatment completion was evaluated through the rate of temporary treatment interruptions, permanent treatment discontinuations and lapatinib dose reductions. Toxicity was evaluated via a selected subset of adverse events of interest (AEI). Risk factors for both treatment completion outcomes and toxicity were investigated, including comorbidities and use of 5 or more co-medications at randomization.
A total of 430 patients ≥ 65year were eligible. Median age was 68 (range 65-80). In comparison with the younger cohort, older patients had a significantly higher number of comorbidities at randomization (p < 0.001). Treatment completion outcomes were worse, particularly in the trastuzumab + lapatinib arm. Adverse events of interest were likewise more common in the trastuzumab + lapatinib arm with higher AEI rates (63.4% in younger vs 78.0% in older, p < 0.001). Concomitant chemotherapy was associated with worse treatment completion outcomes among older patients.
Trastuzumab plus lapatinib was significantly more toxic among older patients and had worse treatment completion. Trastuzumab was generally well tolerated.
Trastuzumab plus lapatinib was significantly more toxic among older patients and had worse treatment completion. Trastuzumab was generally well tolerated.Radioactive cerium and other lanthanides can be transported through the aquatic system into foodstuffs and then be incorporated by humans. Information on the uncertainty of reported dose coefficients for exposed members of the public is then needed for risk analysis. In this study, uncertainties of dose coefficients due to the ingestion of the radionuclides 141Ce and 144Ce were estimated. According to the schema of internal dose calculation, a general statistical method based on the propagation of uncertainty was developed. The method takes into account the uncertainties contributed by the biokinetic models and by the so-called S values. These S-values were derived by using Monte Carlo radiation transport simulations with five adult non-reference voxel computational phantoms that have been developed at Helmholtz Zentrum München, Germany. Random and Latin hypercube sampling techniques were applied to sample parameters of biokinetic models and S values. The uncertainty factors, expressed as the square root of the 97.5th and 2.5th percentile ratios, for organ equivalent dose coefficients of 141Ce were found to be in the range of 1.2-5.1 and for 144Ce in the range of 1.2-7.4. The uncertainty factor of the detriment-weighted dose coefficient for 141Ce is 2.5 and for 144Ce 3.9. It is concluded that a general statistical method for calculating the uncertainty of dose coefficients was developed and applied to the lanthanide cerium. The dose uncertainties obtained provide improved dose coefficients for radiation risk analysis of humans. Furthermore, these uncertainties can be used to identify those parameters most important in internal dose calculations by applying sensitivity analyses.Forest dieback due to climate change poses a risk to mountain forests throughout the world, and has severe consequences in terms of lost ecosystem services for forest stakeholders. This contribution aims to analyze how forest stakeholders perceive forest dieback, and the way in which they adapt to it. We conducted qualitative in-depth interviews in three mid-mountain case study areas in France, Germany, and China, enabling a cross-comparison of different settings affected by forest dieback. Results show that forest dieback is not a new phenomenon for stakeholders who consider that it has increased over the last few decades, due to rising temperatures and extreme weather events. In all survey areas, respondents consider forest dieback as tangible proof of climate change, identifying context-specific impacts with varying levels of severity. Cause-effect relationships are not easy to establish. Forest stakeholders are unable to determine whether climate change is a triggering or aggravating factor. For adaptive strategies, respondents can be grouped into three main profiles proactive, reactive, and wait-and-see forest owners. These types of stakeholders differ in terms of their investment capacities, economic dependency, emotional attachment to forests, knowledge level, and capacity to obtain actionable information through participation in institutional networks.An amendment to this paper has been published and can be accessed via a link at the top of the paper.To assess the impact of a brief training for obstetricians and midwives about screening for domestic violence during pregnancy follow-up and to identify barriers to a routine enquiry. A monocentric quasi-experimental study was performed in an obstetrics department in Paris, France. We asked patients during their pregnancy follow-up to complete a survey describing their demographic characteristics. They were also asked if a health professional had screened them for domestic violence during the current pregnancy. Exclusion criteria were refusal and inability to complete the survey alone. Health professionals attended a brief training about domestic violence. The intervention provided general information about domestic violence to alert health professionals (prevalence, risk factors, consequences on women's health, pregnancy, and children) and guidelines on screening and how to deal with women disclosing domestic violence. They also had to complete a survey about their knowledge and practice concerning domestic the difficulty to identify victims. There was no increased screening for domestic violence during pregnancy follow-up after a brief training of obstetricians and midwives. An early training during medical studies or more extensive training for professionals could be more efficient.Satellite DNAs (satDNA) are fast-evolving repetitive sequences organized in large tandem arrays, with characteristic enrichment in heterochromatin. Knowledge about evolutionary dynamics of this genome fraction is mostly restricted to its characterization in species with monocentric chromosomes, i.e., localized centromeres. In holocentric species, with non-localized centromeres, satDNAs have been largely ignored. Here we advance the understanding of satDNA evolution among holocentric species by characterization of the most abundant satDNAs in the hemipteran Holhymenia histrio, integrating genomic and chromosomal analyses. High plasticity at chromosomal and molecular levels was noticed for 34 satDNAs populating H. histrio genome. One satDNA family in particular (HhiSat01-184) was highly amplified on multiple chromosomes and also highly polymorphic. Our data support the emergence of a new satDNA family from this abundant satDNA, confined to a single chromosome. Moreover, we present new information about composition of a peculiar chromosome in Coreidae, the m-chromosome, and of the X chromosome. Overall, the molecular and chromosomal patterns for satDNAs in the holocentric species H. histrio seem to be similar to those observed in monocentric species.Acephate is widely used in agriculture, but its poisonous metabolites and poor sorption characteristics make it a serious environmental pollutant and toxicant to human health. To screen novel bacteria for biodegradation of acephate and uncover its degradation pathway, a strain called NDZ that is capable of utilizing acephate as a sole carbon and energy source was isolated from severely contaminated cultivated land. The bacterium was identified as Bacillus paramycoides based on 16S rDNA sequence analyses. The growth and degradation capacities of B. paramycoides NDZ under different conditions were studied using optical density at 600 nm (OD600) and high-performance liquid chromatography (HPLC). The results showed that B. paramycoides NDZ can grow well with acephate as its sole carbon source (OD600 = 0.76), and degraded about 76% of acephate in mineral salt medium with an initial concentration of 500 mg/L within 48 h. The results of response surface methodology revealed the optimal conditions for degradation was 36 ℃ and pH 6.
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