Disentangling the roles of aneuploidy, chromosomal instability and tumour heterogeneity in developing resistance to cancer therapies.

Aneuploidy is defined as the cellular state of having a number of chromosomes that deviates from a multiple of the normal haploid chromosome number of a given organism. Aneuploidy can be present in a static state: Down syndrome individuals stably maintain an extra copy of chromosome 21 in their cells. In cancer cells, however, aneuploidy is usually present in combination with chromosomal instability (CIN) which leads to a continual generation of new chromosomal alterations and the development of intratumour heterogeneity (ITH). The prevalence of cells with specific chromosomal alterations is further shaped by evolutionary selection, for example, during the administration of cancer therapies. Aneuploidy, CIN and ITH have each been individually associated with poor prognosis in cancer, and a wealth of evidence suggests they contribute, either alone or in combination, to cancer therapy resistance by providing a reservoir of potential resistant states, or the ability to rapidly evolve resistance. A full understanding of the contribution and interplay between aneuploidy, CIN and ITH is required to tackle therapy resistance in cancer patients. However, these characteristics often co-occur and are intrinsically linked, presenting a major challenge to defining their individual contributions. Moreover, their accurate measurement in both experimental and clinical settings is a technical hurdle. Here, we attempt to deconstruct the contribution of the individual and combined roles of aneuploidy, CIN and ITH to therapy resistance in cancer, and outline emerging approaches to measure and disentangle their roles as a step towards integrating these principles into cancer therapeutic strategy

Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study

Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’ Handbook, and the process was repeated. Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies

Valorizing the Human Capital Within Organizations : A Competency Based Approach

Changes in the business environment and in the nature of work itself require the implementation of integrated and flexible methodologies in competencies’ definition in order to valorize the human capital and achieve organizational targets in a future-oriented perspective. However, extant research suggests that the available approaches to competency definition are more focused on describing past behaviors than on anticipating future requirements. Therefore, this study endeavors to provide a competency-based model that supports the top management in the identification of the competencies employees should posses, highlighting crucial competencies that can translate the strategy and vision of the organization into behaviors, skills, and terms that people can easily understand and implement. The results of our explorative case study led us to identify a set of competencies (digital/analytical/technical/adaptive/combinative/proactive), classified following the Knowledge Skills Attitudes (KSA) model, that collectively lead to a successful definition of future-oriented competencies.© 2019 Springer. This is a post-peer-review, pre-copyedit version of an article published in Advances in Human Factors, Business Management and Society. AHFE 2018. The final authenticated version is available online at: https://doi.org/10.1007/978-3-319-94709-9_6fi=vertaisarvioitu|en=peerReviewed

Gossip in organisations: Contexts, consequences and controversies

This article examines the key themes surrounding gossip including its contexts, the various outcomes (positive and negative) of gossip as well as a selection of challenges and controversies. The challenges which are highlighted revolve around definitional issues, methodological approaches, and ethical considerations. Our analysis suggests that the characteristics and features of gossip lend itself to a process-oriented approach whereby the beginning and, particularly, end points of gossip are not always easily identified. Gossip about a subject or person can temporarily disappear only for it to re-surface at some later stage. In addition, questions pertaining to the effects of gossip and ethical-based arguments depend on the nature of the relationships within the gossip triad (gossiper, listener/respondent and target)

Cognitive and environmental predictors of early literacy skills

Not all young children benefit from book exposure in preschool age. It is claimed that the ability to hold information in mind (short-term memory), to ignore distraction (inhibition), and to focus attention and stay focused (sustained attention) may have a moderating effect on children’s reactions to the home literacy environment. In a group of 228 junior kindergarten children with a native Dutch background, with a mean age of 54.29 months (SD = 2.12 months), we explored therefore the relationship between book exposure, cognitive control and early literacy skills. Parents filled in a HLE questionnaire (book sharing frequency and an author recognition checklist as indicator of parental leisure reading habits), and children completed several tests in individual sessions with the researcher (a book-cover recognition test, PPVT, letter knowledge test, the subtests categories and patterns of the SON, and cognitive control measures namely digit span of the KABC, a peg tapping task and sustained attention of the ANT). Main findings were: (1) Children’s storybook knowledge mediated the relationship between home literacy environment and literacy skills. (2) Both vocabulary and letter knowledge were predicted by book exposure. (3) Short-term memory predicted vocabulary over and above book exposure. (4) None of the cognitive control mechanisms moderated the beneficial effects of book exposure

Allelic Exchange of Pheromones and Their Receptors Reprograms Sexual Identity in Cryptococcus neoformans

Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining “sexes” known as mating types and is controlled by components of mating type (MAT) loci. MAT–encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and α) that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a) replaced the pheromone and pheromone receptor of the other (α). We discovered that these “αa” cells effectively adopt a new mating type (that of a cells); they sense and respond to α factor, they elicit a mating response from α cells, and they fuse with α cells. In addition, αa cells lose the α cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between α and αa strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT–encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen

Socio-economic status, racial composition and the affordability of fresh fruits and vegetables in neighborhoods of a large rural region in Texas

<p>Abstract</p> <p>Background</p> <p>Little is known about how affordability of healthy food varies with community characteristics in rural settings. We examined how the cost of fresh fruit and vegetables varies with the economic and demographic characteristics in six rural counties of Texas.</p> <p>Methods</p> <p>Ground-truthed data from the Brazos Valley Food Environment Project were used to identify all food stores in the rural region and the availability and lowest price of fresh whole fruit and vegetables in the food stores. Socioeconomic characteristics were extracted from the 2000 U.S. Census Summary Files 3 at the level of the census block group. We used an imputation strategy to calculate two types of price indices for both fresh fruit and fresh vegetables: a <it>high variety </it>and a <it>basic </it>index; and evaluated the relationship between neighborhood economic and demographic characteristics and affordability of fresh produce, using linear regression models.</p> <p>Results</p> <p>The mean cost of meeting the USDA recommendation of fruit consumption from a high variety basket of fruit types in our sample of stores was just over $27.50 per week. Relying on the three most common fruits lowered the weekly expense to under$17.25 per week, a reduction of 37.6%. The effect of moving from a high variety to a low variety basket was much less when considering vegetable consumption: a 4.3% decline from $29.23 to$27.97 per week. Univariate regression analysis revealed that the cost of fresh produce is not associated with the racial/ethnic composition of the local community. However, multivariate regression showed that holding median income constant, stores in neighborhoods with higher percentages of Black residents paid more for fresh fruits and vegetables. The proportion of Hispanic residents was not associated with cost in either the univariate or multivariate analysis.</p> <p>Conclusion</p> <p>This study extends prior work by examining the affordability of fresh fruit and vegetables from food stores in a large rural area; and how access to an affordable supply of fresh fruit and vegetables differs by neighborhood inequalities. The approach and findings of this study are relevant and have important research and policy implications for understanding access and availability of affordable, healthy foods.</p