Reporting standards for studies of diagnostic test accuracy in dementia: The STARDdem Initiative.

OBJECTIVE To provide guidance on standards for reporting studies of diagnostic test accuracy for dementia disorders. METHODS An international consensus process on reporting standards in dementia and cognitive impairment (STARDdem) was established, focusing on studies presenting data from which sensitivity and specificity were reported or could be derived. A working group led the initiative through 4 rounds of consensus work, using a modified Delphi process and culminating in a face-to-face consensus meeting in October 2012. The aim of this process was to agree on how best to supplement the generic standards of the STARD statement to enhance their utility and encourage their use in dementia research. RESULTS More than 200 comments were received during the wider consultation rounds. The areas at most risk of inadequate reporting were identified and a set of dementia-specific recommendations to supplement the STARD guidance were developed, including better reporting of patient selection, the reference standard used, avoidance of circularity, and reporting of test-retest reliability. CONCLUSION STARDdem is an implementation of the STARD statement in which the original checklist is elaborated and supplemented with guidance pertinent to studies of cognitive disorders. Its adoption is expected to increase transparency, enable more effective evaluation of diagnostic tests in Alzheimer disease and dementia, contribute to greater adherence to methodologic standards, and advance the development of Alzheimer biomarkers.

Sustainability principles put into practice: case studies of network analysis in Swiss climate change adaptation

Climate adaptation policies increasingly incorporate sustainability principles into their design and implementation. Since successful adaptation by means of adaptive capacity is recognized as being dependent upon progress toward sustainable development, policy design is increasingly characterized by the inclusion of state and non-state actors (horizontal actor integration), cross-sectoral collaboration, and inter-generational planning perspectives. Comparing four case studies in Swiss mountain regions, three located in the Upper Rhone region and one case from western Switzerland, we investigate how sustainability is put into practice. We argue that collaboration networks and sustainability perceptions matter when assessing the implementation of sustainability in local climate change adaptation. In other words, we suggest that adaptation is successful where sustainability perceptions translate into cross-sectoral integration and collaboration on the ground. Data about perceptions and network relations are assessed through surveys and treated via cluster and social network analysis.

Structural Studies of Transition Metal Complexes with 4,5-Bis(2-pyridylmethylsulfanyl)-4‘,5‘-ethylenedithiotetrathiafulvalene: Probing Their Potential for the Construction of Multifunctional Molecular Assemblies

Three divalent transition metal complexes of 4,5-bis(2-pyridylmethylsulfanyl)-4‘,5‘-ethylenedithiotetrathiafulvalene have been prepared and crystallographically characterized. The isostructural Co(II) and the Ni(II) complexes show octahedral geometries around the metal ions with the coordination sites occupied by the pyridyl nitrogen atoms and the thioether sulfur atoms of the ligand and cis coordination of the halide ions. Cyclic voltammetry reveals that the complexation leads to a small anodic shift in the first oxidation potential of the TTF system.

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to allhadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of s = 7 TeV and correspond to an integrated luminosity of 4.6 fb−1. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum pT > 320 GeV and pseudorapidity |η| < 1.9, is measured to be σ + = ± W Z 8.5 1.7 pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques.

Synthesis, spectral, and anti-microbial studies of thioiminium iodides and amine hydrochlorides

To avoid the undesired deprotonation during the addition of organolithium and organomagnesium reagents to ketones, the thioiminium salts, easily prepared from lactams and amides are converted into 2,2-disubstituted and 2-monosubstituted amines by reaction with simple nucleophiles such as organocerium and organocopper reagents. The reaction of thioiminium iodides with organocerium reagents derived by transmetalation of corresponding lithium reagents with anhydrous cerium(III) chloride has been investigated. These thioiminium iodides act as good electrophiles and accept alkylceriums towards bisaddition. The newly synthesized amines have been characterized by 1H and 13C NMR, IR and mass spectra. The amines have been converted into their hydrochlorides and characterized by COSY. These hydrochlorides have been subjected to antimicrobial screening with clinically isolated microorganisms, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi and Candida albicans. The hydrochlorides show quite good activity against these bacteria and fungus.

Chemical studies of elements with Z ⩾ 104 in gas phase

Chemical investigations of superheavy elements in the gas-phase, i.e. elements with Z≥104Z≥104, allow assessing the influence of relativistic effects on their chemical properties. Furthermore, for some superheavy elements and their compounds quite unique gas-phase chemical properties were predicted. The experimental verification of these properties yields supporting evidence for a firm assignment of the atomic number. Prominent examples are the high volatility observed for HsO4 or the very weak interaction of Cn with gold surfaces. The unique properties of HsO4 were exploited to discover the doubly-magic even–even nucleus 270Hs and the new isotope 271Hs. The combination of kinematic pre-separation and gas-phase chemistry allowed gaining access to a new class of relatively fragile compounds, the carbonyl complexes of elements Sg through Mt. A not yet resolved issue concerns the interaction of Fl with gold surfaces. While competing experiments agree on the fact that Fl is a volatile element, there are discrepancies concerning its adsorption on gold surfaces with respect to its daughter Cn. The elucidation of these and other questions amounts to the fascination that gas-phase chemical investigations exert on current research at the extreme limits of chemistry today.

Decomposition studies of group 6 hexacarbonyl complexes. Part 1: Production and decomposition of Mo(CO)6 and W(CO)6

Chemical studies of superheavy elements require fast and efficient techniques, due to short half-lives and low production rates of the investigated nuclides. Here, we advocate for using a tubular flow reactor for assessing the thermal stability of the Sg carbonyl complex – Sg(CO)6. The experimental setup was tested with Mo and W carbonyl complexes, as their properties are established and supported by theoretical predictions. The suggested approach proved to be effective in discriminating between the thermal stabilities of Mo(CO)6 and W(CO)6. Therefore, an experimental verification of the predicted Sg–CO bond dissociation energy seems to be feasible by applying this technique. By investigating the effect of 104,105Mo beta-decay on the formation of 104,105Tc carbonyl complex, we estimated the lower reaction time limit for the metal carbonyl synthesis in the gas phase to be more than 100 ms. We examined further the influence of the wall material of the recoil chamber, the carrier gas composition, the gas flow rate, and the pressure on the production yield of 104Mo(CO)6, so that the future stability tests with Sg(CO)6 can be optimized accordingly.

Optimized on-line enantioselective capillary electrophoretic method for kinetic and inhibition studies of drug metabolism mediated by cytochrome P450 enzymes.

Pharmacokinetic and pharmacodynamic properties of a chiral drug can significantly differ between application of the racemate and single enantiomers. During drug development, the characteristics of candidate compounds have to be assessed prior to clinical testing. Since biotransformation significantly influences drug actions in an organism, metabolism studies represent a crucial part of such tests. Hence, an optimized and economical capillary electrophoretic method for on-line studies of the enantioselective drug metabolism mediated by cytochrome P450 enzymes was developed. It comprises a diffusion-based procedure, which enables mixing of the enzyme with virtually any compound inside the nanoliter-scale capillary reactor and without the need of additional optimization of mixing conditions. For CYP3A4, ketamine as probe substrate and highly sulfated γ-cyclodextrin as chiral selector, improved separation conditions for ketamine and norketamine enantiomers compared to a previously published electrophoretically mediated microanalysis method were elucidated. The new approach was thoroughly validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. The determined parameters were found to be comparable to literature data obtained with different techniques. The presented method constitutes a miniaturized and cost-effective tool, which should be suitable for the assessment of the stereoselective aspects of kinetic and inhibition studies of cytochrome P450-mediated metabolic steps within early stages of the development of a new drug.

Reliability studies of the skew normal distribution

It has been observed in various practical applications that data do not conform to the normal distribution, which is symmetric with no skewness. The skew normal distribution proposed by Azzalini(1985) is appropriate for the analysis of data which is unimodal but exhibits some skewness. The skew normal distribution includes the normal distribution as a special case where the skewness parameter is zero. In this thesis, we study the structural properties of the skew normal distribution, with an emphasis on the reliability properties of the model. More specifically, we obtain the failure rate, the mean residual life function, and the reliability function of a skew normal random variable. We also compare it with the normal distribution with respect to certain stochastic orderings. Appropriate machinery is developed to obtain the reliability of a component when the strength and stress follow the skew normal distribution. Finally, IQ score data from Roberts (1988) is analyzed to illustrate the procedure.

Deformation Studies of Tungsten-Gold Contacts at the Nanometer Scale.

The deformation behavior of atomically clean, nanometer sized tungsten / gold contacts was studied at room temperature in ultra-high vacuum. An instrument that combines atomic force microscopy (AFM), scanning tunneling microscopy (STM), and field ion microscopy (FIM) into a single experimental apparatus was designed, constructed, and calibrated. A cross-hair force sensor having a spring constant of - 442 N/m was developed and its motion was monitored during indentation experiments with a differential interferometer. Tungsten tips of controlled size (12.8 nm < tip radius < 2 1.6 nm) were first shaped and characterized using FIM and then indented into a Au (1 10) single crystal to depths ranging from 1.5 nrn to 18 nm using the force sensor. Continuum mechanics models were found to be valid in predicting elastic deformation during initial contact and plastic zone depths despite our small size regime. Multiple discrete yielding events lasting < 1.5 ms were observed during the plastic deformation regime; at the yield points a maximum value for the principal shear stress was measured to be 5 + 1 GPa. During tip withdrawal, "pop-out" events relating to material relaxation within the contact were observed. Adhesion between the tip and sample led to experimental signatures that suggest neck formation prior to the break of contact. STM images of indentation holes revealed various shapes that can be attributed to the (1 1 1 ) (1 10) crystallographic slip system in gold. FIM images of the tip after indentation showed no evidence of tip damage