Indicators of inequality: Classification and selection of ethnic health disparity indicators

Classification and selection of ethnic disparity health indicators in New Zealand

The Size of the Problem: NAO Report - Tackling Obesity in England

Powerpoint presentation by Rob Pridequx from the National Audit office

Clonotype selection and composition of human CD8 T cells specific for persistent herpes viruses varies with differentiation but is stable over time.

Protection from reactivation of persistent herpes virus infection is mediated by Ag-specific CD8 T cell responses, which are highly regulated by still poorly understood mechanisms. In this study, we analyzed differentiation and clonotypic dynamics of EBV- and CMV-specific T cells from healthy adults. Although these T lymphocytes included all subsets, from early-differentiated (EM/CD28(pos)) to late-differentiated (EMRA/CD28(neg)) stages, they varied in the sizes/proportions of these subsets. In-depth clonal composition analyses revealed TCR repertoires, which were highly restricted for CMV- and relatively diverse for EBV-specific cells. Virtually all virus-specific clonotypes identified in the EMRA/CD28(neg) subset were also found within the pool of less differentiated "memory" cells. However, striking differences in the patterns of dominance were observed among these subsets, because some clonotypes were selected with differentiation while others were not. Late-differentiated CMV-specific clonotypes were mostly characterized by TCR with lower dependency on CD8 coreceptor interaction. Yet all clonotypes displayed similar functional avidities, suggesting a compensatory role of CD8 in the clonotypes of lower TCR avidity. Importantly, clonotype selection and composition of each virus-specific subset upon differentiation was highly preserved over time, with the presence of the same dominant clonotypes at specific differentiation stages within a period of 4 years. Remarkably, clonotypic distribution was stable not only in late-differentiated but also in less-differentiated T cell subsets. Thus, T cell clonotypes segregate with differentiation, but the clonal composition once established is kept constant for at least several years. These findings reveal novel features of the highly sophisticated control of steady state protective T cell activity in healthy adults.

Healthy child, healthy future - Speech and language therapy: Factsheet for parents 5. Does my child have a voice problem?

This factsheet describes voice disorders such as 'hoarseness' in children and what parents can do to help their child with a voice problem.

The robustness of the weak selection approximation for the evolution of altruism against strong selection.

The weak selection approximation of population genetics has made possible the analysis of social evolution under a considerable variety of biological scenarios. Despite its extensive usage, the accuracy of weak selection in predicting the emergence of altruism under limited dispersal when selection intensity increases remains unclear. Here, we derive the condition for the spread of an altruistic mutant in the infinite island model of dispersal under a Moran reproductive process and arbitrary strength of selection. The simplicity of the model allows us to compare weak and strong selection regimes analytically. Our results demonstrate that the weak selection approximation is robust to moderate increases in selection intensity and therefore provides a good approximation to understand the invasion of altruism in spatially structured population. In particular, we find that the weak selection approximation is excellent even if selection is very strong, when either migration is much stronger than selection or when patches are large. Importantly, we emphasize that the weak selection approximation provides the ideal condition for the invasion of altruism, and increasing selection intensity will impede the emergence of altruism. We discuss that this should also hold for more complicated life cycles and for culturally transmitted altruism. Using the weak selection approximation is therefore unlikely to miss out on any demographic scenario that lead to the evolution of altruism under limited dispersal.

Disseny d'un sistema de gestió per a una cambra de congelació robotitzada de masses congelades.

Alguns dels grans fabricants del sector de les masses congelades fan servir robots per a l'emmagatzematge, servei i gestió dels productes de les cambres de congelació. Aquests robots només emmagatzemen i serveixen palets de caixes d'un mateix tipus de producte; així, doncs, només són útils quan el client és un gran consumidor, com un distribuïdor o una delegació, però no un petit comerç, com un restaurant o una fleca, els quals també són clients potencials del fabricant. Per tant, el problema es planteja en el moment de servir els clients que tenen problemes d'emmagatzematge, els quals es veuen obligats a fer comandes de diversos productes, que, a més, en total no fan ni de bon tros un palet sencer. A partir d'aquí la idea és dissenyar un sistema, emprant la tècnica de l'orientació a objectes (O-O), que gestioni un conjunt de robots que, a més d'emmagatzemar i gestionar una cambra de congelació, siguin capaços de servir les comandes fent una selecció de caixes de productes concrets, és a dir, les que sol·licita el client que ha fet la comanda per caixes i no per palets. Per qüestions d'organització i d'estocs, aquests robots han de ser independents dels altres, és a dir, han de treballar en una cambra independent de la dels robots que treballen per palets (actualment aquesta feina la fan treballadors dins una cambra independent de la dels robots).

Targeted expression of human CD1d in transgenic mice reveals independent roles for thymocytes and thymic APCs in positive and negative selection of Valpha14i NKT cells.

CD1d-dependent invariant Valpha14 (Valpha14i) NKT cells are innate T lymphocytes expressing a conserved semi-invariant TCR, consisting, in mice, of the invariant Valpha14-Jalpha18 TCR alpha-chain paired mostly with Vbeta8.2 and Vbeta7. The cellular requirements for thymic positive and negative selection of Valpha14i NKT cells are only partially understood. Therefore, we generated transgenic mice expressing human CD1d (hCD1d) either on thymocytes, mainly CD4+ CD8+ double positive, or on APCs, the cells implicated in the selection of Valpha14i NKT cells. In the absence of the endogenous mouse CD1d (mCD1d), the expression of hCD1d on thymocytes, but not on APCs, was sufficient to select Valpha14i NKT cells that proved functional when activated ex vivo with the Ag alpha-galactosyl ceramide. Valpha14i NKT cells selected by hCD1d on thymocytes, however, attained lower numbers than in control mice and expressed essentially Vbeta8.2. The low number of Vbeta8.2+ Valpha14i NKT cells selected by hCD1d on thymocytes was not reversed by the concomitant expression of mCD1d, which, instead, restored the development of Vbeta7+ Valpha14i NKT cells. Vbeta8.2+, but not Vbeta7+, NKT cell development was impaired in mice expressing both hCD1d on APCs and mCD1d. Taken together, our data reveal that selective CD1d expression by thymocytes is sufficient for positive selection of functional Valpha14i NKT cells and that both thymocytes and APCs may independently mediate negative selection.

Selection of peptides and synthesis of pentameric peptabody molecules reacting specifically with ErbB-2 receptor.

The HER-2/ErbB-2 oncoprotein is overexpressed in human breast and ovarian adenocarcinomas and is clearly associated with the malignant phenotype. Although no specific ligand for this receptor has been positively identified, ErbB-2 was shown to play a central role in a network of interactions with the related ErbB-1, ErbB-3 and ErbB-4 receptors. We have selected new peptides binding to ErbB-2 extracellular domain protein (ECD) by screening 2 newly developed constrained and unconstrained random hexapeptide phage libraries. Out of 37 phage clones, which bound specifically to ErbB-2 ECD, we found 6 constrained and 10 linear different hexapeptide sequences. Among the latter, 5 consensus motifs, all with a common methionine and a positively charged residue at positions 1 and 3, respectively, were identified. Furthermore, 3 representative hexapeptides were fused to a coiled-coil pentameric recombinant protein to form the so-called peptabodies recently developed in our laboratory. The 3 peptabodies bound specifically to the ErbB-2 ECD, as determined by enzyme-linked immunosorbent assay and BIAcore analysis and to tumor cells overexpressing ErbB-2, as shown by flow cytometry. Interestingly, one of the free selected linear peptides and all 3 peptabodies inhibited the proliferation of tumor cells overexpressing ErbB-2. In conclusion, a novel type of ErbB-2-specific ligand is described that might complement presently available monoclonal antibodies.

Selection on age at first and at last reproduction in the long-lived Alpine Swift Apus melba

The way an organism spreads its reproduction over time is defined as a life-history trait, and selection is expected to favour life-history traits associated with the highest fitness return. We use a long-term dataset of 277 life histories to investigate the shape and strength of selection acting on the age at first reproduction and at last reproduction in the long-lived Alpine Swift. Both traits were under strong directional selection, but in opposite directions, with selection favouring birds starting their reproductive career early and being able to reproduce for longer. There was also evidence for stabilising selection acting on both traits, suggesting that individuals should nonetheless refrain from reproducing in their first 2 years of life (i.e. when inexperienced), and that reproducing after 7 years of age had little effect on lifetime fitness, probably due to senescence.

Winter habitat selection by two sympatric forest grouse in western Switzerland: implications for conservation

Two endangered tetraonids, the capercaillie (Tetrao urogallus) and the hazel grouse (Bonasa bonasia rupestris), are sympatric throughout part of their distribution range in central Europe. Precise information on their specific habitat requirements is needed if the coexistence of both species in exploited forests is to be maintained. We quantified winter habitat selection for both species in the upper part (1100-1600 m) of the Jura mountains (Switzerland). No preference for altitude or exposure could be detected. Capercaillie preferred open forests (including grazed forests) with a sparse canopy dominated by spruce (Picea abies) and fir (Abies alba), and avoided dense undercanopy and understorey, especially when dominated by spruce and beech (Fagus sylvatica). By contrast, hazel grouse preferred feeding sites with a dense understorey of rowan (Sorbus aucuparia), willow (Salix sp.), beech and spruce. These preferences can be related to the feeding habits and predator avoidance behaviour of both species. Coexistence thus requires a mosaic distribution of habitat types, with a matrix of open forests (30% canopy cover) where fir is favoured, and understorey kept sparse (20%). Group-cuts of mature trees should allow regeneration patches, where a dense understorey (50% cover) should provide suitable habitats for hazel grouse

Development of physiological resistance and its stage specificity in Culex quinquefasciatus after selection with deltamethrin in Assam, India

The study investigated the development and stage specificity of physiological resistance to insecticides in a colony of Culex quinquefasciatus Say (Diptera: Culicidae) mosquitoes, which are vectors of bancroftian filariasis in India, after selection with deltamethrin. Resistance was selected by exposing the larvae to the concentration of deltamethrin that caused 50% mortality in the tested population (i.e., LC50). Under continuous selection pressure, the LC50 increased steadily in subsequent generations. The estimated LC50 for the F0 generation was 0.409 μg/L; the LC50 first displayed a substantial increase in the F5 generation (5.616 μg/L) and reached 121.902 μg/L in the F10 generation. The objective of this study was to establish a deltamethrin-resistant colony to develop a research programme that will study the evolution of physiological resistance patterns and stage-specific resistance responses in Cx. quinquefasciatus larvae and adults under laboratory conditions. An approximately 298-fold increase in resistance was recorded after 10 generations, as evidenced by the resistance ratio (RR50). The progress and effect of the selection pressure in the adult stage was monitored with the World Health Organisation (WHO) diagnostic test. The mortality, as observed using the WHO diagnostic test, declined significantly from the F5 generation (85%) onwards and the highest rate of survival (65%) was observed in the F10 generation.

Using problem-based learning for introducing producer theory and market structure in intermediate microeconomics

This paper shows how instructors can use the problem‐based learning method to introduce producer theory and market structure in intermediate microeconomics courses. The paper proposes a framework where different decision problems are presented to students, who are asked to imagine that they are the managers of a firm who need to solve a problem in a particular business setting. In this setting, the instructors’ role isto provide both guidance to facilitate student learning and content knowledge on a just‐in‐time basis

In Vivo Selection of Fluoroquinolone-Resistant Escherichia coli Isolates Expressing Plasmid-Mediated Quinolone Resistance and Expanded-Spectrum β-Lactamase

A ciprofloxacin-resistant Escherichia coli isolate, isolate 1B, was obtained from a urinary specimen of a Canadian patient treated with norfloxacin for infection due to a ciprofloxacin-susceptible isolate, isolate 1A. Both isolates harbored a plasmid-encoded sul1-type integron with qnrA1 and blaVEB-1 genes. Isolate 1B had amino acid substitutions in gyrase and topoisomerase.