The HeartQoL: Part I. Development of a new core health-related quality of life questionnaire for patients with ischemic heart disease

Background: Evaluation of health-related quality of life (HRQL) is important in improving the quality of patient care. Methods: The HeartQoL Project, with cross-sectional and longitudinal phases, was designed to develop a core ischemic heart disease (IHD) specific HRQL questionnaire, to be called the HeartQoL, for patients with angina, myocardial infarction (MI), or ischemic heart failure. Patients completed a battery of questionnaires and Mokken scaling analysis was used to identify items in the HeartQoL questionnaire. Results: We enrolled 6384 patients (angina, n = 2111, 33.1%; MI, n = 2351, 36.8%; heart failure, n = 1922, 30.1%) across 22 countries and 15 languages. The HeartQoL questionnaire comprises 14-items with 10-item physical and 4-item emotional subscales which are scored from 0 (poor HRQL) to 3 (better HRQL) with a global score if needed. The mean baseline HeartQoL global score was 2.2 (±0.5) in the total group and was different (p < 0.001) by diagnosis (MI, 2.4 ± 0.5; angina, 2.2 ± 0.6; and heart failure, 2.1 ± 0.6). Conclusion: The HeartQoL questionnaire, with global and subscale scores, has the potential to allow clinicians and researchers to (a) assess baseline HRQL, (b) make between-diagnosis comparisons of HRQL, and (c) evaluate change in HRQL in patients with angina, MI, or heart failure with a single IHD-specific HRQL instrument.

Asymmetric cyclopropanation of olefins catalysed by Cu(I) complexes of chiral pyridine-containing macrocyclic ligands (Pc-L*)

The synthesis and characterisation of copper(I) complexes of chiral pyridine-containing macrocyclic ligands (Pc-L*) and their use as catalysts in asymmetric cyclopropanation reactions are reported. All ligands and metal complexes were fully characterised, including crystal structures of some species determined by X-ray diffraction on single crystals. This allowed characterising the very different conformations of the macrocycles which could be induced by different substituents or by metal complexation. The strategy adopted for the ligand synthesis is very flexible allowing several structural modifications. A small library of macrocyclic ligands possessing the same donor properties but with either C-1 or C-2 symmetry was synthesized. Cyclopropane products with both aromatic and aliphatic olefins were obtained in good yields and enantiomeric excesses up to 99%.

Retrospective analysis of a nonforecasted rain-on-snow flood in the Alps – a matter of model limitations or unpredictable nature?

A rain-on-snow flood occurred in the Bernese Alps, Switzerland, on 10 October 2011, and caused significant damage. As the flood peak was unpredicted by the flood forecast system, questions were raised concerning the causes and the predictability of the event. Here, we aimed to reconstruct the anatomy of this rain-on-snow flood in the Lötschen Valley (160 km2) by analyzing meteorological data from the synoptic to the local scale and by reproducing the flood peak with the hydrological model WaSiM-ETH (Water Flow and Balance Simulation Model). This in order to gain process understanding and to evaluate the predictability. The atmospheric drivers of this rain-on-snow flood were (i) sustained snowfall followed by (ii) the passage of an atmospheric river bringing warm and moist air towards the Alps. As a result, intensive rainfall (average of 100 mm day-1) was accompanied by a temperature increase that shifted the 0° line from 1500 to 3200 m a.s.l. (meters above sea level) in 24 h with a maximum increase of 9 K in 9 h. The south-facing slope of the valley received significantly more precipitation than the north-facing slope, leading to flooding only in tributaries along the south-facing slope. We hypothesized that the reason for this very local rainfall distribution was a cavity circulation combined with a seeder-feeder-cloud system enhancing local rainfall and snowmelt along the south-facing slope. By applying and considerably recalibrating the standard hydrological model setup, we proved that both latent and sensible heat fluxes were needed to reconstruct the snow cover dynamic, and that locally high-precipitation sums (160 mm in 12 h) were required to produce the estimated flood peak. However, to reproduce the rapid runoff responses during the event, we conceptually represent likely lateral flow dynamics within the snow cover causing the model to react "oversensitively" to meltwater. Driving the optimized model with COSMO (Consortium for Small-scale Modeling)-2 forecast data, we still failed to simulate the flood because COSMO-2 forecast data underestimated both the local precipitation peak and the temperature increase. Thus we conclude that this rain-on-snow flood was, in general, predictable, but requires a special hydrological model setup and extensive and locally precise meteorological input data. Although, this data quality may not be achieved with forecast data, an additional model with a specific rain-on-snow configuration can provide useful information when rain-on-snow events are likely to occur.

Mechanisms of transcription inhibition by 8-amino-adenosine

Nucleoside analogs are a class of chemotherapeutic agents with tremendous utility in treating viral infections and cancers. Traditional nucleoside analogs are DNA-directed. However, there is a new group of nucleoside analogs that induce cell death by a direct effect on RNA synthesis. The adenosine analog, 8-chloroadenosine, is incorporated into RNA and is currently in clinical trials. Another congener, 8-amino-adenosine has demonstrated toxicity in multiple myeloma cell lines. Like other nucleoside analogs, 8-amino-adenosine must be metabolized to its triphosphate to elicit a cytotoxic effect. Furthermore, 8-amino-adenosine causes a decline of the intracellular ATP pool and inhibits mRNA poly(A) adenylation. ^ Because of the previously known adenosine analog mechanism as well as the scope of the RNA directed nucleoside analog field, I hypothesized there are multiple mechanisms of transcription inhibition mediating 8-amino-adenosine-induced cell death. Prior to investigating these mechanisms, cell death by 8-amino-adenosine was characterized. 8-Amino-adenosine activates PARP cleavage and induces the caspase cascade. 8-Amino-adenosine increases Annexin V binding and the mitochondrial membrane permeability in wild-type MEF cells. In BAX/BAK deficient MEF cells, 8-amino-adenosine decreases the mitochondrial membrane permeability and induces autophagy. ^ Once cell death was characterized, the mechanisms of 8-amino-adenosine transcription inhibition were assessed. It was established that 8-aminoadenosine treatment causes 8-amino-ATP accumulation and decreases the intracellular ATP concentration, resulting in RNA synthesis inhibition. Several other mechanisms are identified. First, a relationship between ATP decline by 8-amino-adenosine or other known ATP synthesis inhibitors and RNA synthesis is established indicating that effects on cellular bioenergy, regardless of the mechanism of ATP decline, can decrease RNA synthesis. Second, 8-aminoadenosine treatment decreases the phosphorylation of serine residues on the RNA polymerase II C-terminal domain which regulates transcription initiation and elongation. Third, evidence is provided to demonstrate 8-amino-ATP is a substrate for RNA synthesis. Fourth, 8-amino-ATP is incorporated at the 3'-terminal position leading to chain termination. Finally, in vitro transcription assays show that 8-amino-ATP may compete with ATP to decrease de novo mRNA synthesis. Overall, this work demonstrates 8-amino-adenosine is a cytotoxic nucleoside analog that functions to inhibit RNA transcription through multiple mechanisms. ^

The unity of the organism; or, The organismal conception of life, by William Emerson Ritter ...

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Letter from Rufus King to William Tudor,

One letter regarding a meeting between the elder William Tudor and the King of England at the Court of Saint James.

The book of common prayer : and administration of the sacraments, and other rites and ceremonies of the church, according to the use of the Church of England ; together with the Psalter, or Psalms of David.

Mode of access: Internet.