A Laser System for the Spectroscopy of Highly-Charged Bismuth Ions

We present and characterize a laser system for the spectroscopy on highly-charged ^209Bi^82+ ions at a wavelength of 243.87 nm. For absolute frequency stabilization, the laser system is locked to a near-infra-red laser stabilized to a rubidium transition line using a transfer cavity based locking scheme. Tuning of the output frequency with high precision is achieved via a tunable rf offset lock. A sample-and-hold technique gives an extended tuning range of several THz in the UV. This scheme is universally applicable to the stabilization of laser systems at wavelengths not directly accessible to atomic or molecular resonances. We determine the frequency accuracy of the laser system using Doppler-free absorption spectroscopy of Te_2 vapour at 488 nm. Scaled to the target wavelength of 244 nm, we achieve a frequency uncertainty of \sigma_{244nm} = 6.14 MHz (one standard deviation) over six days of operation.Comment: Contribution to the special issue on "Trapped Ions" in "Applied Physics B

Variable coordination of amine functionalised N-heterocyclic carbene ligands to Ru, Rh and Rr: C-H and N-H activation and catalytic transfer hydrogenation

Chelating amine and amido complexes of late transition metals are highly valuable bifunctional catalysts in organic synthesis, but complexes of bidentate amine–NHC and amido–NHC ligands are scarce. Hence, we report the reactions of a secondary-amine functionalised imidazolium salt 2a and a primary-amine functionalised imidazolium salt 2b with [( p -cymene)RuCl 2 ] 2 and [Cp*MCl 2 ] 2 (M = Rh, Ir). Treating 2a with [Cp*MCl 2 ] 2 and NaOAc gave the cyclometallated compounds Cp*M(C,C)I (M = Rh, 3 ;M = Ir, 4 ), resulting from aromatic C–H activation. In contrast, treating 2b with [( p -cymene)RuCl 2 ] 2 ,Ag 2 O and KI gave the amine–NHC complex [( p -cymene)Ru(C,NH 2 )I]I ( 5 ). The reaction of 2b with [Cp*MCl 2 ] 2 (M = Rh, Ir), NaO t Bu and KI gave the amine–NHC complex [Cp*Rh(NH 2 )I]I ( 6 ) or the amido–NHC complex Cp*Ir(C,NH)I ( 7 ); both protonation states of the Ir complex could be accessed: treating 7 with trifluoroacetic acid gave the amine–NHC complex [Cp*Ir(C,NH 2 )I][CF 3 CO 2 ]( 8 ). These are the first primary amine– or amido–NHC complexes of Rh and Ir. Solid-state structures of the complexes 3–8 have been determined by single crystal X-ray diffraction. Complexes 5 , 6 and 7 are pre-catalysts for the catalytic transfer hydrogenation of acetophenone to 1-phenylethanol, with ruthenium complex 5 demonstrating especially high reactivity

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk:Rationale and design of the ODYSSEY DM-INSULIN trial

Aims: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. Methods: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening. ≥. 70. mg/dL (1.81. mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24. weeks of alirocumab 75. mg every 2. weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C. ≥. 70. mg/dL at week 8 underwent a blinded dose increase to 150. mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. Results: This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. Conclusion: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy

Less invasive methods of advanced hemodynamic monitoring: principles, devices, and their role in the perioperative hemodynamic optimization.

The monitoring of the cardiac output (CO) and other hemodynamic parameters, traditionally performed with the thermodilution method via a pulmonary artery catheter (PAC), is now increasingly done with the aid of less invasive and much easier to use devices. When used within the context of a hemodynamic optimization protocol, they can positively influence the outcome in both surgical and non-surgical patient populations. While these monitoring tools have simplified the hemodynamic calculations, they are subject to limitations and can lead to erroneous results if not used properly. In this article we will review the commercially available minimally invasive CO monitoring devices, explore their technical characteristics and describe the limitations that should be taken into consideration when clinical decisions are made

Temporal changes in frequency of severe hypoglycemia treated by emergency medical services in types 1 and 2 diabetes:a population-based data-linkage cohort study

Background  Almost 20 years ago, the frequencies of severe hypoglycemia requiring emergency medical treatment were reported in people with types 1 and 2 diabetes in the Tayside region of Scotland. With subsequent improvements in the treatment of diabetes, concurrent with changes in the provision of emergency medical care, a decline in the frequency of severe hypoglycemia could be anticipated. The present population-based data-linkage cohort study aimed to ascertain whether a temporal change has occurred in the incidence rates of hypoglycemia requiring emergency medical services in people with types 1 and 2 diabetes.  Methods  The study population comprised all people with diabetes in Tayside, Scotland over the period 1 January 2011 to 31 December 2012. Patients’ data from different healthcare sources were linked anonymously to measure the incidence rates of hypoglycemia requiring emergency medical services that include treatment by ambulance staff and in hospital emergency departments, and necessitated hospital admission. These were compared with data recorded in 1997–1998 in the same region.  Results  In January 2011 to December 2012, 2029 people in Tayside had type 1 diabetes and 21,734 had type 2 diabetes, compared to 977 and 7678, respectively, in June 1997 to May 1998. In people with type 2 diabetes, the proportion treated with sulfonylureas had declined from 36.8 to 22.4% (p<0.001), while insulin-treatment had increased from 11.7 to 18.7% (p<0.001). The incidence rate of hypoglycemia requiring emergency medical treatment had significantly fallen from 0.115 (95% CI: 0.094–0.136) to 0.082 (0.073–0.092) events per person per year in type 1 diabetes (p<0.001), and from 0.118 (0.095–0.141) to 0.037 (0.003–0.041) in insulin-treated type 2 diabetes (p=0.008). However, the absolute annual number of hypoglycemia events requiring emergency treatment was 1.4-fold higher.  Conclusions  Although from 1998 to 2012 the incidences of hypoglycemia requiring emergency medical services appeared to have declined by a third in type 1 diabetes and by two thirds in insulin-treated type 2 diabetes, because the prevalence of diabetes was higher (2.7 fold), the number of severe hypoglycemia events requiring emergency medical treatment was greater

LDL lowering effect of PCSK9 inhibition is reduced in women

Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol (LDL-C) concentration, and its inhibition reduces the risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the sex-differential effect of either pharmacological or genetic inhibition of PCSK9 on LDL-C levels. Methods and results We meta-analyzed six real-life studies (1216 men and 641 women) that investigated the effects of PCSK9 monoclonal antibodies (mAbs) on LDL-C reduction in men and women. Despite higher LDL-C levels in women at baseline [mean difference (MD) = 17.4 mg/dL, P < 0.0001, women = 175 mg/dL vs. men = 152 mg/dL], the LDL-C reduction under PCSK9 mAb treatment was significantly greater in men (MD = 7.6 mg/dL, 95% confidence interval: 2.7–12.4, P = 0.002) than in women. We tested the sex-related association of the loss-of-function variant PCSK9-R46L with LDL-C plasma levels in 382 813 individuals (219 301 women and 163 512 men) free of lipid-lowering drugs from the UK Biobank general population cohort. The magnitude of LDL-C reduction was larger in men than in women (mean LDL-C difference: –35 mg/dL vs. –26 mg/dL, when comparing homozygous carriers with non-carriers in men and women, respectively). The relationship between PCSK9-R46L and LDL-C was significantly dependent on sex (P for interaction = 7.2e–04). Conclusion These results demonstrate by complementary approaches that the decrease in LDL-C mediated by PCSK9 inhibition is slightly, but significantly, less marked in women than in men. These data reinforce the need for specific studies to develop sex-specific recommendations for the management of ASCVD in women

Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women

Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]