Does Testosterone Mediate the Relationship Between Vitamin D and Prostate Cancer? A Systematic Review and Meta-Analysis Protocol

Abstract Background Evidence from studies on prostate cancer progression have identified vitamin D to be a potentially important nutrient. However, the World Cancer Research Fund and American Institute for Cancer Research have reported the quality of this evidence to be limited and warrant further investigation. We plan to use the recently developed WCRF International/University of Bristol mechanistic systematic review framework to determine whether the observed association between vitamin D and prostate cancer exists through a plausible biological pathway. Methods This protocol sets out how we will perform a systematic review of the literature in human and animal studies. We will search the electronic databases MEDLINE, EMBASE, PubMed, and BIOSIS Citation Index without restrictions on year of publication or language. We will extract data from observational and experimental studies examining two inter-linked pathways in the relationship between vitamin D and prostate cancer progression: (1) vitamin D and testosterone, and (2) testosterone and prostate cancer progression. We focus on testosterone as its actions form a potentially novel intermediate mechanism that was identified via our online literature mining tools. The outcomes of interest include incidence or prevalence of prostate cancer, measures of prostate cancer progression (including biochemical recurrence, local, or distal metastases), and prostate cancer-specific mortality. We will assess study quality and the level of certainty of the evidence. We will analyse data where possible, using meta-analysis with forest plots or albatross plots; otherwise, a narrative synthesis will be performed. Discussion To our knowledge, this will be the first systematic synthesis of the evidence underpinning the vitamin D-testosterone-prostate cancer mechanistic pathway. The results of the review may inform future research, intervention trials, and public health messages

The reinforcement sensitivity theory of personality in children: A new questionnaire

We report the development of a self-report questionnaire of the reinforcement sensitivity theory (RST) of personality for use with children. Focus groups were held with children to sample their experiences of situations modelled on components of three RST systems: fight-flight-freeze system (FFFS, related to fear), behavioural inhibition system (BIS, related to anxiety), and behavioural approach system (BAS, related to approach). The thematic responses formed the conceptual anchors to the development of test items that were examined using exploratory factor analysis in a sample of 288 9–13 year olds. After eliminating items that did not load on their designated factor, or substantially cross-loaded over factors, the original 48 items were reduced to 21 items: 7 items for each of the BIS, FFFS and BAS factors. The separation of the BIS and FFFS items across two factors is consistent with the revised model of RST. We offer this new questionnaire as a RST measure of fundamental motivation and emotion traits in children

Breast Cancer Risk in Young Women in the National Breast Screening Programme: Implications for Applying NICE Guidelines for Additional Screening and Chemoprevention

In the United Kingdom, women at moderate and high risk of breast cancer between the ages of 40 and 49 years are eligible for annual mammographic screening and preventive therapy with tamoxifen. Here, we estimate the numbers of women in a population eligible for this service and the proportion of breast cancers detected in this group compared with the whole population. Wome

Methods for visual mining of genomic and proteomic data atlases

<p>Abstract</p> <p>Background</p> <p>As the volume, complexity and diversity of the information that scientists work with on a daily basis continues to rise, so too does the requirement for new analytic software. The analytic software must solve the dichotomy that exists between the need to allow for a high level of scientific reasoning, and the requirement to have an intuitive and easy to use tool which does not require specialist, and often arduous, training to use. Information visualization provides a solution to this problem, as it allows for direct manipulation and interaction with diverse and complex data. The challenge addressing bioinformatics researches is how to apply this knowledge to data sets that are continually growing in a field that is rapidly changing.</p> <p>Results</p> <p>This paper discusses an approach to the development of visual mining tools capable of supporting the mining of massive data collections used in systems biology research, and also discusses lessons that have been learned providing tools for both local researchers and the wider community. Example tools were developed which are designed to enable the exploration and analyses of both proteomics and genomics based atlases. These atlases represent large repositories of raw and processed experiment data generated to support the identification of biomarkers through mass spectrometry (the PeptideAtlas) and the genomic characterization of cancer (The Cancer Genome Atlas). Specifically the tools are designed to allow for: the visual mining of thousands of mass spectrometry experiments, to assist in designing informed targeted protein assays; and the interactive analysis of hundreds of genomes, to explore the variations across different cancer genomes and cancer types.</p> <p>Conclusions</p> <p>The mining of massive repositories of biological data requires the development of new tools and techniques. Visual exploration of the large-scale atlas data sets allows researchers to mine data to find new meaning and make sense at scales from single samples to entire populations. Providing linked task specific views that allow a user to start from points of interest (from diseases to single genes) enables targeted exploration of thousands of spectra and genomes. As the composition of the atlases changes, and our understanding of the biology increase, new tasks will continually arise. It is therefore important to provide the means to make the data available in a suitable manner in as short a time as possible. We have done this through the use of common visualization workflows, into which we rapidly deploy visual tools. These visualizations follow common metaphors where possible to assist users in understanding the displayed data. Rapid development of tools and task specific views allows researchers to mine large-scale data almost as quickly as it is produced. Ultimately these visual tools enable new inferences, new analyses and further refinement of the large scale data being provided in atlases such as PeptideAtlas and The Cancer Genome Atlas.</p

Widespread Gene Conversion in Centromere Cores

Data from maize show that centromeres strongly suppress crossing over and instead undergo frequent genetic exchange in the form of gene conversion

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Molecular Squares, Coordination Polymers and Mononuclear Complexes Supported by 2,4-Dipyrazolyl-6H-1,3,5-triazine and 4,6-Dipyrazolylpyrimidine Ligands

The Fe[BF4]2 complex of 2,4-di(pyrazol-1-yl)-6H-1,3,5-triazine (L1) is a high-spin molecular square, [{Fe(L1)}4(μ-L1)4][BF4]8, whose crystals also contain the unusual HPzBF3 (HPz = pyrazole) adduct. Three other 2,4-di(pyrazol-1-yl)-6H-1,3,5-triazine derivatives with different pyrazole substituents (L2-L4) are unstable in the presence of first row transition ions, but form mononuclear, polymeric or molecular square complexes with silver(I). Most of these compounds involve bis-bidentate di(pyrazolyl)triazine coordination, which is unusual for that class of ligand, and the molecular squares encapsulate one or two BF4‒, ClO4‒ or SbF6‒ ions through combinations of anion...π, Ag...X and/or C‒H...X (X = O or F) interactions. Treatment of Fe[NCS]2 or Fe[NCSe]2 with 4,6-di(pyrazol-1-yl)-2H-pyrimidine (L5) or its 2-methyl and 2-amino derivatives L6 and L7) yields mononuclear [Fe(NCE)2L2] and/or the 1D coordination polymers catena-[Fe(NCE)2(μ-L)] (E = S or Se, L = L5-L7). Alcohol solvates of isomorphous [Fe(NCS)2L2] and [Fe(NCSe)2L2] compounds show different patterns of intermolecular hydrogen bonding, reflecting the acceptor properties of the anion ligands. These iron compounds are all high-spin, although annealing solvated crystals of [Fe(NCSe)2(L5)2] affords a new phase exhibiting an abrupt, low-temperature spin transition. Catena-[Fe(H2O)2(μ-L5)][ClO4]2 is a coordination polymer of alternating cis and trans iron centres