Mapping Functions in Health-Related Quality of Life: Mapping From Two Cancer-Specific Health-Related Quality-of-Life Instruments to EQ-5D-3L.

BACKGROUND: Clinical trials in cancer frequently include cancer-specific measures of health but not preference-based measures such as the EQ-5D that are suitable for economic evaluation. Mapping functions have been developed to predict EQ-5D values from these measures, but there is considerable uncertainty about the most appropriate model to use, and many existing models are poor at predicting EQ-5D values. This study aims to investigate a range of potential models to develop mapping functions from 2 widely used cancer-specific measures (FACT-G and EORTC-QLQ-C30) and to identify the best model. METHODS: Mapping models are fitted to predict EQ-5D-3L values using ordinary least squares (OLS), tobit, 2-part models, splining, and to EQ-5D item-level responses using response mapping from the FACT-G and QLQ-C30. A variety of model specifications are estimated. Model performance and predictive ability are compared. Analysis is based on 530 patients with various cancers for the FACT-G and 771 patients with multiple myeloma, breast cancer, and lung cancer for the QLQ-C30. RESULTS: For FACT-G, OLS models most accurately predict mean EQ-5D values with the best predicting model using FACT-G items with similar results using tobit. Response mapping has low predictive ability. In contrast, for the QLQ-C30, response mapping has the most accurate predictions using QLQ-C30 dimensions. The QLQ-C30 has better predicted EQ-5D values across the range of possible values; however, few respondents in the FACT-G data set have low EQ-5D values, which reduces the accuracy at the severe end. CONCLUSIONS: OLS and tobit mapping functions perform well for both instruments. Response mapping gives the best model predictions for QLQ-C30. The generalizability of the FACT-G mapping function is limited to populations in moderate to good health

Synthesis and Characterization of Carbon-Bridged (1(n))(2,6)pyridinophanes.

Pyridine-containing heterophanes, which possess a rigid non-flexible framework, similar to that of porphyrin backbones, are ideal structures to probe the electronic and/or steric effects within a highly electron-rich cavity. The syntheses of heteromacrocycles incorporating the 2,6-pyridino moiety are described. 2-Bromo-6-lithiopyridine, generated from 2,6-dibromopyridine and n-butyllithium, was used to synthesize 2,6-bis (2\sp\prime-(6\sp\prime-bromopicolinoyl)) pyridine and bis-2-(6-bromopyridyl)ketone in 36% and 63% yield, respectively. Ketalization of these ketones was accomplished by either standard acidic or basic conditions. To model a nucleophilic substitution route for cyclization of the resulting ketals, lithioacetonitriles were allowed to react with bromopyridines to produce symmetrical and unsymmetrical cyanomethine adducts in more than 47% yield. Reaction of 2,6-bis- (2\sp\prime-(6\sp\prime-bromopyridyl)-1,3-dioxolan-2-yl) pyridine or 2,2-bis-2\sp\prime-(6\sp\prime-bromopyridyl)-1,3-dioxolane with lithioacetonitrile afforded (1\sb{\rm n}) (2,6)pyridinophanes (n = 3,4), in which the pyridine rings were coupled with ketal and cyanomethine functionalities. At 80\sp\circC, cyclocondensation via nucleophilic substitution favors macrocycle formation because the intermediates are held in the desired syn-conformation by a metal ion template effect. The ketal and nitrile groups of the initially generated macrocycles were hydrolyzed under acidic conditions. Hydrolysis of the nitrile was accompanied by decarboxylation to produce methylenic intermediates (143 and 152), which were oxidized with SeO\sb2 to afford the desired triketone 115 and tetraketone 125, respectively. Alternatively, oxidation of the $\alpha$,$\beta$-unsaturated nitrile tautomers with m-chloroperbenzoic acid to a keto group; followed by deketalization under acidic conditions afforded the same ketones. Triketone 115 and tetraketone 125 contain only sp\sp2 carbon atoms and should be essentially planar; however, due predominantly to N,N-electron repulsions within the confines of the cavity, deformations from planarity were observed. The dihedral angles of pyridines in triketone 115 are 35.4, 41.4, and 46.5\sp\circ, respectively. Wittig reactions and the Knoevenagel condensations on the bridging carbonyl groups in triketone 115 were unsuccessful, but facile monohemiketalization of 115 was observed. X-ray analysis of a Cu(II) complex isolated from ethanol confirmed the presence of a hemiethyl ketal (178). Upon exposure to air, precursor 143 of triketone 115 underwent oxidization to afford dimeric (1\sb3) (2,6)-pyridinophane, which was subsequently dehydrogenated with either DDQ or air. X-ray data of these dimers confirm the juxtaposition of the two electron-rich cores

Using Rasch analysis to form plausible health states amenable to valuation: the development of CORE-6D from CORE-OM in order to elicit preferences for common mental health problems

Purpose: To describe a new approach for deriving a preference-based index from a condition specific measure that uses Rasch analysis to develop health states. Methods: CORE-OM is a 34-item instrument monitoring clinical outcomes of people with common mental health problems. CORE-OM is characterised by high correlation across its domains. Rasch analysis was used to reduce the number of items and response levels in order to produce a set of unidimensionally-behaving items, and to generate a credible set of health states corresponding to different levels of symptom severity using the Rasch item threshold map. Results: The proposed methodology resulted in the development of CORE-6D, a 2-dimensional health state description system consisting of a unidimensionally-behaving 5-item emotional component and a physical symptom item. Inspection of the Rasch item threshold map of the emotional component helped identify a set of 11 plausible health states, which, combined with the physical symptom item levels, will be used for the valuation of the instrument, resulting in the development of a preference-based index. Conclusions: This is a useful new approach to develop preference-based measures where the domains of a measure are characterised by high correlation. The CORE-6D preference-based index will enable calculation of quality adjusted life years in people with common mental health problems.Rasch analysis; health-related quality of life; condition-specific measure; preference-based health; health states; CORE-6D; CORE-OM; mental health; quality-adjusted life years

Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.

The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response

Population genetic structure and direct observations reveal sex-reversed patterns of dispersal in a cooperative bird

Sex-biased dispersal is pervasive and has diverse evolutionary implications, but the fundamental drivers of dispersal sex biases remain unresolved. This is due in part to limited diversity within taxonomic groups in the direction of dispersal sex biases, which leaves hypothesis testing critically dependent upon identifying rare reversals of taxonomic norms. Here, we use a combination of observational and genetic data to demonstrate a rare reversal of the avian sex bias in dispersal in the cooperatively breeding white-browed sparrow weaver (Plocepasser mahali). Direct observations revealed that (i) natal philopatry was rare, with both sexes typically dispersing locally to breed, and (ii), unusually for birds, males bred at significantly greater distances from their natal group than females. Population genetic analyses confirmed these patterns, as (i) corrected Assignment index (AIc), FST tests and isolation-by-distance metrics were all indicative of longer dispersal distances among males than females, and (ii) spatial autocorrelation analysis indicated stronger within-group genetic structure among females than males. Examining the spatial scale of extra-group mating highlighted that the resulting ‘sperm dispersal’ could have acted in concert with individual dispersal to generate these genetic patterns, but gamete dispersal alone cannot account entirely for the sex differences in genetic structure observed. That leading hypotheses for the evolution of dispersal sex biases cannot readily account for these sex-reversed patterns of dispersal in white-browed sparrow weavers highlights the continued need for attention to alternative explanations for this enigmatic phenomenon. We highlight the potential importance of sex differences in the distances over which dispersal opportunities can be detected

Structure of Titan's mid-range magnetic tail: Cassini magnetometer observations during the T9 flyby

We analyze the magnetic structure of Titan's mid-range magnetic tail (5-6 Titan radii downstream from the moon) during Cassini's T9 flyby. Cassini magnetometer (MAG) measurements reveal a well-defined, induced magnetic tail consisting of two lobes and a distinct central current sheet. MAG observations also indicate that Saturn's background magnetic field is close to the moon's orbital plane and that the magnetospheric flow has a significant component in the Saturn-Titan direction. The analysis of MAG data in a coordinate system based on the orientation of the background magnetic field and an estimation of the incoming flow direction suggests that Titan's magnetic tail is extremely asymmetric. An important source of these asymmetries is the connection of the inbound tail lobe and the outbound tail lobe to the dayside and nightside hemispheres of Titan, respectively. Another source could be the perturbations generated by changes in the upstream conditions

Spin-orbit torque induced dipole skyrmion motion at room temperature

We demonstrate deterministic control of dipole-field-stabilized skyrmions by means of spin-orbit torques arising from heavy transition-metal seed layers. Experiments are performed on amorphous Fe/Gd multilayers that are patterned into wires and exhibit stripe domains and dipole skyrmions at room temperature. We show that while the domain walls and skyrmions are achiral on average due to lack of Dzyaloshinskii-Moriya interactions, the N\'eel-like closure domain walls at each surface are chiral and can couple to spin-orbit torques. The current-induced domain evolutions are reported for different magnetic phases, including disordered stripe domains, coexisting stripes and dipole skyrmions and a closed packed dipole skyrmion lattice. The magnetic textures exhibit motion under current excitations with a current density ~10^8 A/m2. By comparing the motion resulting from magnetic spin textures in Fe/Gd films with different heavy transition-metal interfaces, we confirm spin currents can be used to manipulate achiral dipole skyrmions via spin-orbit torques.Comment: 23 pages, 8 figure

User-driven design of robot costume for child-robot interactions among children with cognitive impairment

The involvement of arts and psychology elements in robotics research for children with cognitive impairment is still limited. However, the combination of robots, arts, psychology and education in the development of robots could significantly contribute to the improvement of social interaction skills among children with cognitive impairment. In this article, we would like to share our work on building and innovating the costume of LUCA's robot, which incorporating the positive psychological perspectives and arts values for children with cognitive impairment. Our goals are (1) to educate arts students in secondary arts school on the importance of social robot appearance for children with cognitive impairment, and (2) to select the best costume for future child-robot interaction study with children with cognitive impairments