Bayesian Analysis of Femtosecond Pump-Probe Photoelectron-Photoion Coincidence Spectra with Fluctuating Laser Intensities

This paper employs Bayesian probability theory for analyzing data generated in femtosecond pump-probe photoelectron-photoion coincidence (PEPICO) experiments. These experiments allow investigating ultrafast dynamical processes in photoexcited molecules. Bayesian probability theory is consistently applied to data analysis problems occurring in these types of experiments such as background subtraction and false coincidences. We previously demonstrated that the Bayesian formalism has many advantages, amongst which are compensation of false coincidences, no overestimation of pump-only contributions, significantly increased signal-to-noise ratio, and applicability to any experimental situation and noise statistics. Most importantly, by accounting for false coincidences, our approach allows running experiments at higher ionization rates, resulting in an appreciable reduction of data acquisition times. In addition to our previous paper, we include fluctuating laser intensities, of which the straightforward implementation highlights yet another advantage of the Bayesian formalism. Our method is thoroughly scrutinized by challenging mock data, where we find a minor impact of laser fluctuations on false coincidences, yet a noteworthy influence on background subtraction. We apply our algorithm to data obtained in experiments and discuss the impact of laser fluctuations on the data analysis

Chiral (SO)–N–(SO) Sulfoxide Pincer Complexes of Mg, Rh, and Ir: N–H Activation and Selective Sulfoxide Reduction upon Ligand Coordination

Multigram quantities of the optically pure amino−bis-sulfoxide ligand (S,S)-bis(4-tert-butyl-2-(ptolylsulfinyl) phenyl)amine ((S,S)-3) are accessible by in situ lithiation of bis(2-bromo-4-tert-butylphenyl)amine (1) followed by a nucleophilic displacement reaction with Andersen’s sulfinate 2. Deprotonation of (S,S)-3 with MgPh2 yields the magnesium amido−bis-sulfoxide salt (S,S)-4 quantitatively. Metathetical exchange of (S,S)-4 with [RhCl(COE)2]2 affords the optically pure pseudo-C2-symmetric Rh(I)−amido bissulfoxide pincer complex mer-(R,R)-[Rh(bis(4-(tert-butyl)-2- (p-tolylsulfinyl)phenyl)amide)(COE)] (mer-(R,R)-5). This complex reacts with 3 equiv of HCl to give the facial Rh(III) complex fac-(S,R,R)-[Rh(bis(4-(tert-butyl)-2-(p-tolylsulfinyl)- phenyl)amine)Cl3] (fac-(S,R,R)-6), in which one of the sulfoxide functions has been reduced to the sulfide and in which the resulting sulfoxide−sulfide−amine ligand is facially coordinated. The same complexes 5 and 6 form in a 1:2 ratio in a disproportionation reaction when [RhCl(COE)2]2 is treated with 2 equiv of neutral ligand 3. N−H activation is directly observed in the reaction of [IrCl(COE)2]2 with 3, affording the amido−hydrido−Ir(III) complex [Ir(bis(4-(tert-butyl)-2-(ptolylsulfinyl) phenyl)amide)(Cl)(H)(COE)] (8)

Chiral amino-phosphine and amido-phosphine complexes of Ir and Mg. Catalytic applications in olefin hydroamination

The reactions of rac- and (S,S)-trans-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine (ANDEN) with PClPh2 in the presence of NEt3 yield the chiral amino-phosphine ligands rac-6 and (S,S)-6, respectively, on multi-gram scales. Both forms of 6 react quantitatively with MgPh2 to afford the C2-symmetric, N-bound Mg amidophosphine complexes rac-7 and (S,S)-7. The former crystallizes as a racemic conglomerate, which is a rare occurrence. Mixing (S,S)- or rac-6 with [IrCl(COE)2]2 leads in both cases to the homochiral dinuclear chloro-bridged P-ligated aminophosphine iridium complexes (S,S,S,S)-9 and rac-9 in excellent yields. X-ray quality single crystals only grow as the racemic compound (or ‘true racemate’) rac-9 thanks to its lowered solubility. In the coordinating solvent CH3CN, rac-9 transforms in high yield into mononuclear Ir-complex rac-10. The crystal structures of compounds rac-6, (S,S)-7, rac-9, and rac-10 reveal the ambidentate nature of the P–N function: amide-coordination in the Mg-complex (S,S)-7 and P-chelation of the softer Ir(I) centres in complexes rac-9 and rac-10. Furthermore, the crystal structures show flexible, symmetry lowering seven-membered P-chelate rings in the Ir complexes and a surprising amount of deformation within the ANDEN backbone. The simulation of this deformation by DFT and SCF calculations indicates low energy barriers. (S,S)-7 and (S,S,S,S)-9 catalyze the intra- and intermolecular hydroamination of alkenes, respectively: 5 mol% of (S,S)-7 affords 2-methyl-4,4′-diphenylcyclopentyl amine quantitatively (7% ee), and 2.5 mol% of (S,S,S,S)-9 in the presence of 5.0 mol% co-catalyst (LDA, PhLi, or MgPh2) gives exo-(2-arylamino)bornanes in up to 68% yield and up to 16% ee

Increased Motor-Impairing Effects of the Neuroactive Steroid Pregnanolone in Mice with Targeted Inactivation of the GABA(A) Receptor gamma 2 Subunit in the Cerebellum

Endogenous neurosteroids and neuroactive steroids have potent and widespread actions on the brain via inhibitory GABA(A) receptors. In recombinant receptors and genetic mouse models their actions depend on the alpha, beta, and delta subunits of the receptor, especially on those that form extrasynaptic GABA(A) receptors responsible for non-synaptic (tonic) inhibition, but they also act on synaptically enriched gamma 2 subunit containing receptors and even on alpha beta binary receptors. Here we tested whether behavioral sensitivity to the neuroactive steroid agonist 5 beta-pregnan-3 alpha-ol-20-one is altered in genetically engineered mouse models that have deficient GABA(A) receptor mediated synaptic inhibition in selected neuronal populations. Mouse lines with the GABA(A) receptor gamma 2 subunit gene selectively deleted either in parvalbumin-containing cells (including cerebellar Purkinje cells), cerebellar granule cells, or just in cerebellar Purkinje cells were trained on the accelerated rotating rod and then tested for motor impairment after cumulative intraperitoneal dosing of 5 beta-pregnan-3 alpha-ol-20-one. Motor impairing effects of 5 beta-pregnan-3 alpha-ol-20-one were strongly increased in all three mouse models in which gamma 2 subunit-dependent synaptic GABA(A) responses in cerebellar neurons were genetically abolished. Furthermore, rescue of postsynaptic GABA(A) receptors in Purkinje cells normalized the effect of the steroid. Anxiolytic/explorative effects of the steroid in elevated plus maze and light:dark exploration tests in mice with Purkinje cell gamma 2 subunit inactivation were similar to those in control mice. The results suggest that, when the deletion of gamma 2 subunit has removed synaptic GABA(A) receptors from the specific cerebellar neuronal populations, the effects of neuroactive steroids solely on extrasynaptic alpha beta or alpha beta delta receptors lead to enhanced changes in the cerebellum-generated behavior.Peer reviewe

A paired-kidney allocation study found superior survival with HLA-DR compatible kidney transplants in the Eurotransplant Senior Program

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching. We used Kaplan-Meier estimates and competing risk analysis to assess all cause mortality and kidney graft failure, respectively. The log-rank test and Cox proportional hazards regression were used for comparisons. Within ESP, matching for HLA-DR antigens was associated with a significantly lower five-year risk of mortality (hazard ratio 0.71; 95% confidence interval 0.53-0.95) and significantly lower cause-specific hazards for kidney graft failure and return to dialysis at one year (0.55; 0.35-0.87) and five years (0.73; 0.53-0.99) post-transplant. Allocation based on HLA-DR matching resulted in longer cold ischemia (mean difference 1.00 hours; 95% confidence interval: 0.32-1.68) and kidney offers with a significantly shorter median dialysis vintage of 2.4 versus 4.1 yrs. in ESP without matching. Thus, our allocation based on HLA-DR matching improved five-year patient and kidney allograft survival. Hence, our paired allocation study suggests a superior outcome of HLA-DR matching in the context of old-for-old kidney transplantation.</p

The effectiveness of the Austrian disease management programme for type 2 diabetes: a cluster-randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Disease management programmes (DMPs) are costly and impose additional work load on general practitioners (GPs). Data on their effectiveness are inconclusive. We therefore conducted a cluster-randomised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care.</p> <p>Methods</p> <p>All GPs of Salzburg-province were invited to participate. After cluster-randomisation by district, all patients with diabetes type 2 were recruited consecutively from 7-11/2007. The DMP, consisting mainly of physician and patient education, standardised documentation and agreement on therapeutic goals, was implemented in the intervention group while the control group received usual care. We aimed to show superiority of the intervention regarding metabolic control and process quality. The primary outcome measure was a change in HbA1c after one year. Secondary outcomes were days in the hospital, blood pressure, lipids, body mass index (BMI), enrolment in patient education and regular guideline-adherent examination. Blinding was not possible.</p> <p>Results</p> <p>92 physicians recruited 1489 patients (649 intervention, 840 control). After 401 ± 47 days, 590 intervention-patients and 754 controls had complete data. In the intention to treat analysis (ITT) of all 1489 patients, HbA1c decreased 0.41% in the intervention group and 0.28% in controls. The difference of -0.13% (95% CI -0.24; -0.02) was significant at p = 0.026. Significance was lost in mixed models adjusted for baseline value and cluster-effects (adjusted mean difference -0.03 (95% CI -0.15; 0.09, p = 0.607). Of the secondary outcome measures, BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments (-0.53 kg/m²; 95% CI -1.03;-0.02; p = 0.014 and -0.10 mmol/l; 95% CI -0.21; -0.003; p = 0.043). Additionally, more patients received patient education (49.5% vs. 20.1%, p < 0.0001), eye- (71.0% vs. 51.2%, p < 0.0001), foot examinations (73.8% vs. 45.1%, p < 0.0001), and regular HbA1c checks (44.1% vs. 36.0%, p < 0.01) in the intervention group.</p> <p>Conclusion</p> <p>The Austrian DMP implemented by statutory health insurance improves process quality and enhances weight reduction, but does not significantly improve metabolic control for patients with type 2 diabetes mellitus. Whether the small benefit seen in secondary outcome measures leads to better patient outcomes, remains unclear.</p> <p>Trial Registration</p> <p>Current Controlled trials Ltd., ISRCTN27414162.</p

Federated Identity Management for Research Collaborations

This white-paper expresses common requirements of Research Communities seeking to leverage Identity Federation for Authentication and Authorisation. Recommendations are made to Stakeholders to guide the future evolution of Federated Identity Management in a direction that better satisfies research use cases. The authors represent research communities, Research Services, Infrastructures, Identity Federations and Interfederations, with a joint motivation to ease collaboration for distributed researchers. The content has been edited collaboratively by the Federated Identity Management for Research (FIM4R) Community, with input sought at conferences and meetings in Europe, Asia and North America

Development and Psychometric Evaluation of an Item Bank for Computerized Adaptive Testing of the EORTC Insomnia Dimension in Cancer Patients (EORTC CAT-SL)

To further advance assessment of patient-reported outcomes, the European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group has developed computerized adaptive test (CAT) versions of all EORTC Quality of Life Core Questionnaire (QLQ-C30) scales/items. The aim of this study was to develop and evaluate an item bank for CAT measurement of insomnia (CAT-SL). In line with the EORTC guidelines, the developmental process comprised four phases: (I) defining the concept insomnia and literature search, (II) selection and formulation of new items, (III) pre-testing and (IV) field-testing, including psychometric analyses of the final item bank. In phase I, the literature search identified 155 items that were compatible with our conceptualisation of insomnia, including both quantity and quality of sleep. In phase II, following a multistep-approach, this number was reduced to 15 candidate items. Pre-testing of these items in cancer patients (phase III) resulted in an item list of 14 items, which were field-tested among 1094 patients in phase IV. Psychometric evaluations showed that eight items could be retained in a unidimensional model. The final item bank yielded greater measurement precision than the original QLQ-C30 insomnia item. It was estimated that administering two or more items from the insomnia item bank with CAT results in a saving in sample size between approximately 15–25%. The 8-item EORTC CAT-SL item bank facilitates precise and efficient measurement of insomnia as part of the EORTC CAT system of health-related quality life assessment in both clinical research and practice

Key lessons from the DACCIWA project for operational meteorological services

This document describes the conclusions of the EU-funded project Dynamics- Aerosol-Chemistry-Cloud Interactions in West Africa (DACCIWA) directly relevant to operational meteorological services. DACCIWA produced the most comprehensive observational dataset of the atmosphere over densely populated southern West Africa to date and used this dataset to foster our understanding of atmospheric processes, and to evaluate dynamical models and satellite data. With this document DACCIWA aims to help improve atmospheric predictions across time-scales, which are important for the development of greater resilience of the West African population to hazardous weather and climate change