A randomized trial to determine the impact on compliance of a psychophysical peripheral cue based on the Elaboration Likelihood Model

Objective: Non-compliance in clinical studies is a significant issue, but causes remain unclear. Utilizing the Elaboration Likelihood Model of persuasion, this study assessed the psychophysical peripheral cue ‘Interactive Voice Response System (IVRS) call frequency’ on compliance. Methods: 71 participants were randomized to once daily (OD), twice daily (BID) or three times daily (TID) call schedules over two weeks. Participants completed 30-item cognitive function tests at each call. Compliance was defined as proportion of expected calls within a narrow window (± 30 min around scheduled time), and within a relaxed window (− 30 min to + 4 h). Data were analyzed by ANOVA and pairwise comparisons adjusted by the Bonferroni correction. Results: There was a relationship between call frequency and compliance. Bonferroni adjusted pairwise comparisons showed significantly higher compliance (p = 0.03) for the BID (51.0%) than TID (30.3%) for the narrow window; for the extended window, compliance was higher (p = 0.04) with OD (59.5%), than TID (38.4%). Conclusion: The IVRS psychophysical peripheral cue call frequency supported the ELM as a route to persuasion. The results also support OD strategy for optimal compliance. Models suggest specific indicators to enhance compliance with medication dosing and electronic patient diaries to improve health outcomes and data integrity respectively

Effect of Prior Bilateral Oophorectomy on the Presentation of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

Purpose: To compare the presentation of invasive breast cancer in BRCA1 and BRCA2 mutation carriers with and without prior bilateral oophorectomy. Patients and methods: Women with a BRCA1 or BRCA2 mutation with the diagnosis of invasive breast cancer were identified from ten cancer genetics clinics. The medical history, medical treatment records and pathology reports for the breast cancers were reviewed. Information was abstracted from medical charts, including history (and date) of oophorectomy, date of breast cancer diagnosis, stage of disease, and pathologic characteristics of the breast cancer. Women with prior bilateral oophorectomy were matched by age, year of diagnosis, and mutation with one or more women who had two intact ovaries at the time of breast cancer diagnosis. Characteristics of the breast tumours were compared between the two groups

Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance

INTRODUCTION: The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by profiling a large cohort of breast tumours in tissue microarrays (TMAs) using immunohistochemistry (IHC). METHODS: We included 4, 125 patients enrolled in the SEARCH population-based study with tumours represented in TMAs and classified into molecular subtype according to a validated IHC-based five-marker scheme. IHC was used to detect CD44/CD24, ALDH1A1, aldehyde dehydrogenase family 1 member A3 (ALDH1A3) and integrin alpha-6 (ITGA6). A 'Total CSC' score representing expression of all four CSC markers was also investigated. Association with breast cancer specific survival (BCSS) at 10 years was assessed using a Cox proportional-hazards model. This study was complied with REMARK criteria. RESULTS: In ER negative cases, multivariate analysis showed that ITGA6 was an independent prognostic factor with a time-dependent effect restricted to the first two years of follow-up (hazard ratio (HR) for 0 to 2 years follow-up, 2.4; 95% confidence interval (95% CI), 1.2 to 4.8; P = 0.009). The composite 'Total CSC' score carried independent prognostic significance in ER negative cases for the first four years of follow-up (HR for 0 to 4 years follow-up, 1.3; 95% CI, 1.1 to 1.6; P = 0.006). CONCLUSIONS: Breast CSC markers do not identify identical subpopulations in primary tumours. Both ITGA6 and a composite Total CSC score show independent prognostic significance in ER negative disease. The use of multiple markers to identify tumours enriched for CSCs has the greatest prognostic value. In the absence of more specific markers, we propose that the effective translation of the CSC hypothesis into patient benefit will necessitate the use of a panel of markers to robustly identify tumours enriched for CSCs

Ocean current patterns drive the worldwide colonization of eelgrass (Zostera marina)

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Changes in vertical ice extent along the East Antarctic Ice Sheet margin in western Dronning Maud Land – initial field and modelling results of the MAGIC-DML collaboration

Constraining numerical ice sheet models by comparison with observational data is crucial to address the interactions between cryosphere and climate at a wide range of scales. Such models are tested and refined by comparing model predictions of past ice geometries with field-based reconstructions from geological, geomorphological, and ice core data. However, for the East Antarctic Ice sheet, there is a critical gap in the empirical data necessary to reconstruct changes in ice sheet geometry in the Dronning Maud Land (DML) region. In addition, there is poor control on the regional climate history of the ice sheet margin, because ice-core locations, where detailed reconstructions of climate history exist, are located on high inland domes. This leaves numerical models ofregional glaciation history in this near-coastal area largely unconstrained. MAGIC-DML is an ongoing Swedish-US-Norwegian-German-UK collaboration with a focus on improvingice sheet models of the western DML margin by combining advances in modeling with filling critical data gaps regarding the timing and pattern of ice-surface changes. A combination of geomorphological mapping using remote sensing data, field observations, cosmogenic nuclide surface exposure dating, and numerical ice sheetmodeling are being used in an iterative manner to produce a comprehensive reconstruction of the glacial historyof western DML. Here, we present an overview of the project, field evidence for formerly higher ice surfaces and in-situ cosmogenic nuclide measurements from the 2016/17 expedition. Preliminary field evidence indicate that interior sectors of DML have experienced a general decrease in ice sheet thickness since the late Miocene, with potential episodes of increasing thickness in the late Pleistocene (700-300 ka, 250-75 ka). To aid in interpreting these field data, new high-resolution ice sheet model reconstructions, constraining ice sheet configurations during key episodes, are presented

Mid-Pleistocene ice sheet fluctuations from cosmogenic nuclide field constraints in western Dronning Maud Land, Antarctica

The East Antarctic Ice Sheet (EAIS) is generally assumed to have been relatively insensitive to Quaternary climat echange. However, recent studies have shown potential instabilities in coastal, marine sectors of the EAIS. In addition, long-term climate reconstructions and modelling experiments indicate the potential for significant changes in ice volume and ice sheet configuration since the Pliocene. Hence, more empirical evidence for ice surface and ice volume changes is required to discriminate between contrasting inferences. MAGIC-DML is an ongoing Swedish-US-Norwegian-German-UK collaboration focused on improving ice sheetm odels by filling critical data gaps that exist in our knowledge of the timing and pattern of ice surface changes along the western Dronning Maud Land (DML) margin and combining this with advances in numerical techniques. As part of the project, field studies in the 2016/17 and 2017/18 austral summers targeted selected sites spanning accessible altitudes in the Heimefrontfjella, Vestfjella, Ahlmannryggen, Borgmassivet, and Kirwanveggen nunatakranges for in situcosmogenic nuclide sampling. Comparing concentrations of nuclides with widely differing half-lives in bedrock and erratics from a range of altitudes above modern ice surfaces can provide information on ice sheet fluctuations and complex burial and exposure histories, and thus, past configurations of non-erosive ice. Quartz-bearing rock types were sampled and analyzed for 10Be (t1/21.4 My),14C (t1/25.7 ky),26Al (t1/2705ky), and 21Ne (stable), and mafic lithologies for36Cl (t1/2301 ky). Results thus far for 3210Be and 26Al isotope pairs complemented with seven21Ne measurements have yielded some consistent patterns of paleoglaciation for the western DML margin. Eight out of fourteen bedrock samples from high-elevation (1700-2238 m a.s.l.) ridges and summits return some of the oldest exposure ages in Antarctica and have consistent 10Be,26Al, and 21Ne minimum apparent exposure ages of 1.8-4.1 Ma. Initial results therefore indicate that parts of the ice sheet marginal to the Antarctic plateau, along the Heimefrontfjella range, generally have experienced a decrease in ice thickness since the late Miocene. Another six bedrock samples (1556-1732 ma.s.l.) fall in the 300-700 ka range, and they all show significant burial. At face value, perhaps this indicates aregional ice sheet surface above 1700 m a.s.l. for much of the Plio-early Pleistocene. All other samples analyzedto date are erratics from lower elevation and more coastal sites (10 from nunataks at 553-1400 m a.s.l., and 6 froma surface moraine at 1385 m a.s.l.), exhibiting ages between 59 and 275 ka, save for two (4 and 6 ka). Whereas almost all of the nunatak erratics (including the young ones) show significant burial durations, five of the six surface moraine samples do not. These 2016/17 field samples are not yet leading to conclusive age constraints but already start to paint a picture of the western DML margin being relatively stable although there was possibly one or more episodes of relatively limited ice thickening during the last 700 ka

IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health

Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote

The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance

Aging impacts transcriptomes but not genomes of hormone-dependent breast cancers

Age is one of the most important risk factors for human malignancies, including breast cancer; in addition, age-at-diagnosis has been shown to be an independent indicator of breast cancer prognosis. However, except for inherited forms of breast cancer, there is little genetic or epigenetic understanding of the biological basis linking aging with sporadic breast cancer incidence and its clinical behavior