High Dimensional Classification with combined Adaptive Sparse PLS and Logistic Regression

Motivation: The high dimensionality of genomic data calls for the development of specific classification methodologies, especially to prevent over-optimistic predictions. This challenge can be tackled by compression and variable selection, which combined constitute a powerful framework for classification, as well as data visualization and interpretation. However, current proposed combinations lead to instable and non convergent methods due to inappropriate computational frameworks. We hereby propose a stable and convergent approach for classification in high dimensional based on sparse Partial Least Squares (sparse PLS). Results: We start by proposing a new solution for the sparse PLS problem that is based on proximal operators for the case of univariate responses. Then we develop an adaptive version of the sparse PLS for classification, which combines iterative optimization of logistic regression and sparse PLS to ensure convergence and stability. Our results are confirmed on synthetic and experimental data. In particular we show how crucial convergence and stability can be when cross-validation is involved for calibration purposes. Using gene expression data we explore the prediction of breast cancer relapse. We also propose a multicategorial version of our method on the prediction of cell-types based on single-cell expression data. Availability: Our approach is implemented in the plsgenomics R-package.Comment: 9 pages, 3 figures, 4 tables + Supplementary Materials 8 pages, 3 figures, 10 table

Addiction through the Ages: a review of the development of concepts and ideas about addiction in European countries since the nineteenth century and the role of international organisations in the process

The work on addiction through the ages proceeded through 4 interlinked studies: The emergence of concepts of addiction across Europe at the national level, 1860-1980 The framing of the alcohol question at the international alcohol conferences The role of the World Health Organisation (WHO) and its expert committees in defining addiction from the 1940s to the early twenty first century The role of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) in defining concepts of addiction The long view of addiction concepts at the country level over time points to continuities and changes across countries. They have also played a significant role in international organisations, the pre World War Two alcohol conferences and the World Health Organisation (WHO) after that war. The European level through the European Monitoring Centre on Drugs and Drug Addiction has also come into the picture in more recent times with discussion of a different set of concepts. Although a degree of stability has been achieved around addiction concepts, these still encapsulate a variety of meanings which translate into different treatment and policy approaches and traditions within Europe. By understanding the history of such concepts and how and why they came in and out of use, we can better understand addiction terminology and substance use policy today

'Injections-While-You-Dance': Press Advertisement and Poster Promotion of the Polio Vaccine to British Publics, 1956-1962.

This article discusses the production and dissemination of the emotive and informative messages promoting polio vaccination registration in Britain from 1956-1962 through the lens of public health press advertisements and posters. It argues that as the press reported on the problems which beset the vaccine campaign, and the various publics who could register for the polio vaccination multiplied, the campaign's content changed. Material was adapted to target the presumed emotional and educational needs of newly eligible publics. The article contends that by attending to the emotional content of this campaign, the variety of publics envisioned by the producers may be examined

Addiction in Europe, 1860s-1960s: Concepts and Responses in Italy, Poland, Austria, and the United Kingdom

Concepts play a central part in the formulation of problems and proposed solutions to the use of substances. This article reports the initial results from a cross European historical study, carried out to a common methodology, of the language of addiction and policy responses in two key periods, 1860–1930 and the 1950s and 1960s. It concludes that the language of addiction was varied and nonstandard in the first period. The Anglo-American model of inebriety did not apply across Europe but there was a common focus on theories of heredity and national degeneration. After World War II, there was a more homogenous language but still distinct national differences in emphasis and national interests and policy responses to different substances. More research will be needed to deepen understanding of the conditions under which these changes took place and the social and policy appeal of disease theories

Structural basis of tRNA modification with CO2 fixation and methylation by wybutosine synthesizing enzyme TYW4†

Wybutosine (yW), one of the most complicated modified nucleosides, is found in the anticodon loop of eukaryotic phenylalanine tRNA. This hypermodified nucleoside ensures correct codon recognition by stabilizing codon-anticodon pairings during the decoding process in the ribosome. TYW4 is an S-adenosylmethionine (SAM)-dependent enzyme that catalyzes the final step of yW biosynthesis, methylation and methoxycarbonylation. However, the structural basis for the catalytic mechanism by TYW4, and especially that for the methoxycarbonylation, have remained elusive. Here we report the apo and cofactor-bound crystal structures of yeast TYW4. The structures revealed that the C-terminal domain folds into a β-propeller structure, forming part of the binding pocket for the target nucleoside. A comparison of the apo, SAM-bound, and S-adenosylhomocysteine-bound structures of TYW4 revealed a drastic structural change upon cofactor binding, which may sequester solvent from the catalytic site during the reaction and facilitate product release after the reaction. In conjunction with the functional analysis, our results suggest that TYW4 catalyzes both methylation and methoxycarbonylation at a single catalytic site, and in the latter reaction, the methoxycarbonyl group is formed through the fixation of carbon dioxide

Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep

The use of vaccines including aluminum (Al)–based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injection-site granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher (P <.001) in the lymph nodes of the vaccine group (82.65 µg/g) compared with both adjuvant-only (2.53 µg/g) and control groups (0.96 µg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs

Cancer survivors' experience with telehealth: A systematic review and thematic synthesis

Background: Net survival rates of cancer are increasing worldwide, placing a strain on health service provision. There is a drive to transfer the care of cancer survivors—individuals living with and beyond cancer—to the community and encourage them to play an active role in their own care. Telehealth, the use of technology in remote exchange of data and communication between patients and health care professionals (HCPs), is an important contributor to this evolving model of care. Telehealth interventions are “complex,” and understanding patient experiences of them is important in evaluating their impact. However, a wider view of patient experience is lacking as qualitative studies detailing cancer survivor engagement with telehealth are yet to be synthesized. Objective: To systematically identify, appraise, and synthesize qualitative research evidence on the experiences of adult cancer survivors participating in telehealth interventions, to characterize the patient experience of telehealth interventions for this group. Methods: Medline (PubMed), PsychINFO, Cumulative Index for Nursing and Allied Health Professionals (CINAHL), Embase, and Cochrane Central Register of Controlled Trials were searched on August 14, 2015, and March 8, 2016, for English-language papers published between 2006 and 2016. Inclusion criteria were as follows: adult cancer survivors aged 18 years and over, cancer diagnosis, experience of participating in a telehealth intervention (defined as remote communication or remote monitoring with an HCP delivered by telephone, Internet, or hand-held or mobile technology), and reporting qualitative data including verbatim quotes. An adapted Critical Appraisal Skill Programme (CASP) checklist for qualitative research was used to assess paper quality. The results section of each included article was coded line by line, and all papers underwent inductive analysis, involving comparison, reexamination, and grouping of codes to develop descriptive themes. Analytical themes were developed through an iterative process of reflection on, and interpretation of, the descriptive themes within and across studies. Results: Across the 22 included papers, 3 analytical themes emerged, each with 3 descriptive subthemes: (1) influence of telehealth on the disrupted lives of cancer survivors (convenience, independence, and burden); (2) personalized care across physical distance (time, space, and the human factor); and (3) remote reassurance—a safety net of health care professional connection (active connection, passive connection, and slipping through the net). Telehealth interventions represent a convenient approach, which can potentially minimize treatment burden and disruption to cancer survivors’ lives. Telehealth interventions can facilitate an experience of personalized care and reassurance for those living with and beyond cancer; however, it is important to consider individual factors when tailoring interventions to ensure engagement promotes benefit rather than burden. Conclusions: Telehealth interventions can provide cancer survivors with independence and reassurance. Future telehealth interventions need to be developed iteratively in collaboration with a broad range of cancer survivors to maximize engagement and benefit