The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10−8; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in sperm, and therefore suggest that spermatozoal DNA methylation is an unlikely mediator of intergenerational effects of metabolic traits

Measurement of Cosmic-ray Electrons at TeV Energies by VERITAS

Cosmic-ray electrons and positrons (CREs) at GeV-TeV energies are a unique probe of our local Galactic neighborhood. CREs lose energy rapidly via synchrotron radiation and inverse-Compton scattering processes while propagating within the Galaxy and these losses limit their propagation distance. For electrons with TeV energies, the limit is on the order of a kiloparsec. Within that distance there are only a few known astrophysical objects capable of accelerating electrons to such high energies. It is also possible that the CREs are the products of the annihilation or decay of heavy dark matter (DM) particles. VERITAS, an array of imaging air Cherenkov telescopes in southern Arizona, USA, is primarily utilized for gamma-ray astronomy, but also simultaneously collects CREs during all observations. We describe our methods of identifying CREs in VERITAS data and present an energy spectrum, extending from 300 GeV to 5 TeV, obtained from approximately 300 hours of observations. A single power-law fit is ruled out in VERITAS data. We find that the spectrum of CREs is consistent with a broken power law, with a break energy at 710 $\pm$ 40$_{stat}$ $\pm$ 140$_{syst}$ GeV.Comment: 17 pages, 2 figures, accepted for publication in PR

Signaling in Secret: Pay-for-Performance and the Incentive and Sorting Effects of Pay Secrecy

Key Findings: Pay secrecy adversely impacts individual task performance because it weakens the perception that an increase in performance will be accompanied by increase in pay; Pay secrecy is associated with a decrease in employee performance and retention in pay-for-performance systems, which measure performance using relative (i.e., peer-ranked) criteria rather than an absolute scale (see Figure 2 on page 5); High performing employees tend to be most sensitive to negative pay-for- performance perceptions; There are many signals embedded within HR policies and practices, which can influence employees’ perception of workplace uncertainty/inequity and impact their performance and turnover intentions; and When pay transparency is impractical, organizations may benefit from introducing partial pay openness to mitigate these effects on employee performance and retention

Core outcome domains for early-phase clinical trials of sound-, psychology-, and pharmacology-based interventions to manage chronic subjective tinnitus in adults: the COMIT'ID study protocol for using a Delphi process and face-to-face meetings to establish consensus

Background: The reporting of outcomes in clinical trials of subjective tinnitus indicates that many different tinnitus-related complaints are of interest to investigators, from perceptual attributes of the sound (e.g. loudness) to psychosocial impacts (e.g. quality of life). Even when considering one type of intervention strategy for subjective tinnitus, there is no agreement about what is critically important for deciding whether a treatment is effective. The main purpose of this observational study is therefore to develop Core Outcome Domain Sets for the three different intervention strategies (sound, psychological, and pharmacological) for adults with chronic subjective tinnitus that should be measured and reported in every clinical trial of these interventions. Secondary objectives are to identify the strengths and limitations of our study design for recruiting and reducing attrition of participants, and to explore uptake of the core outcomes. Methods: The ‘Core Outcome Measures in Tinnitus: International Delphi’ (COMIT’ID) study will use a mixed methods approach that incorporates input from healthcare users at the pre-Delphi stage, a modified three round Delphi survey and final consensus meetings (one for each intervention). The meetings will generate recommendations by stakeholder representatives on agreed Core Outcome Domain Sets specific to each intervention. A subsequent step will establish a common cross-cutting Core Outcome Domain Set by identifying the common outcome domains included in all three intervention-specific Core Outcome Domain Sets. To address the secondary objectives, we will gather feedback from participants about their experience of taking part in the Delphi process. We aspire to conduct an observational cohort study to evaluate uptake of the core outcomes in published studies at 7 years following core outcome set publication. Discussion: The COMIT’ID study aims to develop a Core Outcome Domain Set that are agreed as critically important for deciding whether a treatment for subjective tinnitus is effective. Such a recommendation would help to standardise future clinical trials worldwide and so we will determine if participation increases use of the core outcome set in the long term. Trial registration: This project has been registered in the database of the Core Outcome Measures in Effectiveness Trials (COMET) initiative

Empowerment/sexism: Figuring female sexual agency in contemporary advertising

This paper argues that there has been a significant shift in advertising representations of women in recent years, such that rather than being presented as passive objects of the male gaze, young women in adverts are now frequently depicted as active, independent and sexually powerful. This analysis examines contemporary constructions of female sexual agency in advertisements examining three recognizable ‘figures’: the young, heterosexually desiring ‘midriff’, the vengeful woman set on punishing her partner or ex partner for his transgressions, and the ‘hot lesbian’, almost always entwined with her beautiful Other or double. Using recent examples of adverts the paper asks how this apparent ‘agency’ and ‘empowerment’ should be understood. Drawing on accounts of the incorporation or recuperation of feminist ideas in advertising the paper takes a critical approach to these representations, examining their exclusions, their constructions of gender relations and heteronormativity, and the way power is figured within them. A feminist poststructuralist approach is used to interrogate the way in which ‘sexual agency’ becomes a form of regulation in these adverts, that requires the re-moulding of feminine subjectivity to fit the current postfeminist, neoliberal moment in which young women should not only be beautiful but sexy, sexually knowledgeable/practised and always ‘up for it’. The paper makes an original contribution to debates about representations of gender in advertising, to poststructuralist analyses about the contemporary operation of power, and to writing about female ‘sexual agency’ by suggesting that ‘voice’ or ‘agency’ may not be the solution to the ‘missing discourse of female desire' but may in fact be a technology of discipline and regulation

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. Registered on 12 March 2015 revised on 15 March 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1399-9) contains supplementary material, which is available to authorized users