Construction of the Views oN Infant Sleep (VNIS) Questionnaire

Parents' beliefs about infant sleep behaviour vary over time and across cultures. No validated instrument exists to understand parents' pre- and postnatal views on infant sleep behaviours, which may influence their caregiving decisions. The Views oN Infant Sleep Questionnaire (VNIS) will be a tool to assess parents' beliefs in order to facilitate tailored perinatal care, increase the reliability of postnatal self-report measures, allow for cross-cultural comparisons, and provide a baseline for researchers to use in longitudinal studies. We recruited an online sample of 971 female participants who were resident in the United Kingdom, at least 28 weeks pregnant, and at least 18 years of age. The initial questionnaire consisted of 31 questions about infant independence, night-waking, infant feeding, touch, and safety, and items were rated on a 5-point Likert scale. The item pool was reduced to 12 using principal component analysis and a structure was found for the three components “Closeness”, “Independence”, and “Night-waking”. Overall, these results suggest that the VNIS can provide a brief scale to measure different aspects of individuals' beliefs about infant sleep. In further research the VNIS needs to be validated with a confirmatory factor analysis in another sample, and to be tested as a cross-cultural instrument

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

CONTEXT: Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. OBJECTIVE: To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. EVIDENCE ACQUISITION: We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. EVIDENCE SYNTHESIS: We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. CONCLUSIONS: Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. PATIENT SUMMARY: Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility

W boson production at hadron colliders: the lepton charge asymmetry in NNLO QCD

We consider the production of W bosons in hadron collisions, and the subsequent leptonic decay W->lnu_l. We study the asymmetry between the rapidity distributions of the charged leptons, and we present its computation up to the next-to-next-to-leading order (NNLO) in QCD perturbation theory. Our calculation includes the dependence on the lepton kinematical cuts that are necessarily applied to select W-> lnu_l events in actual experimental analyses at hadron colliders. We illustrate the main differences between the W and lepton charge asymmetry, and we discuss their physical origin and the effect of the QCD radiative corrections. We show detailed numerical results on the charge asymmetry in ppbar collisions at the Tevatron, and we discuss the comparison with some of the available data. Some illustrative results on the lepton charge asymmetry in pp collisions at LHC energies are presented.Comment: 37 pages, 21 figure

The interplay of customer experience and commitment

Purpose This research aims to better understand customer experience, as it relates to customer commitment and provides a framework for future research into the intersection of these emerging streams of research. Design/methodology/approach This research contributes to theoretical and practical perspectives on customer experience and its measurement by integrating extant literature with customer commitment and customer satisfaction literature. Findings The breadth of the domains that encompass customer experience – cognitive, emotional, physical, sensorial and social – makes simplistic metrics impossible for gauging the entirety of customers’ experiences. These findings provide strong support of the need for new research into customer experience and customer commitment. Practical implications Given the complexity of customer experience, managers are unlikely to track and manage all relevant elements of the concept. This research provides a framework identifying empirically the most salient attributes of customer experience with particular emphasis on those elements that enhance commitment. This offers insight into service design to correspond with specific commitment and experience dimensions. Originality/value This research is the first to examine the customer experience as it relates to customer commitment – a key factor in customer loyalty, positive word of mouth and other desired outcomes for managers and marketers. This paper provides a framework for future research into these emerging topics. </jats:sec

Using environmental monitoring to complement in-depth qualitative interviews in cold homes research

Cold homes contribute to twenty to forty thousand excess winter deaths each year in the UK and approximately 300,000 hospital admissions. Using fuel poverty as an identifier for those at risk does not always capture everyday exposure to cold homes due to variations in financial trade-offs and behavioural factors. Few fuel poverty studies have combined environmental measurements with qualitative data on lived experiences of fuel poverty and cold homes. This paper looks at the strengths and limitations of using a mixed method, environmental and qualitative interviewing approach. A series of six discreet studies were conducted between 2001 and 2015 using a similar methodology with a mixed methods design where in-depth interviews were conducted alongside temperature and humidity measurements. The research studies found that combining environmental monitoring with qualitative research methods allows both cross validation and triangulation of data in order to provide a richer and more insightful examination into the lives of people living in cold homes. The studies demonstrate how a combined methodological approach can help explain the choices, decisions and behaviour of households experiencing cold homes and fuel poverty. The paper concludes with recommendations for future development and implementation of the research method

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

Parental education and perception of outdoor playing time for preschoolers

Abstract Aim: The objective of this study was to analyze whether or not socioeconomic positions influence outdoor playtime during the week (WK) and on the weekends (WEND). Methods: The sample consisted of 485 (girls; n=223) healthy preschoolers, aged from 3 to 6 years, enrolled in kindergartens from the metropolitan area of Porto, Portugal. Physical Activity (PA) was assessed for 7 consecutive days with an accelerometer. The time playing outdoors during the WK or the WEND was reported by parents. Anthropometric data (weight and height) was collected following standardized protocols. Socioeconomic position was assessed by Parental Education (PE), according to the Portuguese education system. Results: We found differences in time spent playing outdoors either for the WK or WEND, but not for Total PA (TPA), in both sexes. However, regression analysis showed that after age adjustment, BMI and TPA for both sexes, we only found significant associations between low PE (LPE) and high PE (HPE) groups on WK or WEND. However, we found no statistically significant association for boys on the WK (p=0.06). Conclusion: Our findings suggest that socioeconomic position can influence the children’s time spent in outdoor activities, especially on the weekends. This may have implications for future interventions with this age group

An evaluation of a national mass media campaign to raise public awareness of possible lung cancer symptoms in England in 2016 and 2017

This is the final version. Available on open access from Springer Nature via the DOI in this recordBackground. A two-phase ‘respiratory symptoms’ mass media campaign was conducted in 2016 and 2017 in England raising awareness of cough and worsening shortness-of-breath as symptoms warranting a GP visit. Method. A prospectively planned pre-post evaluation was done using routinely collected data on 15 metrics, including: GP attendance, GP referral, emergency presentations, cancers diagnosed (5 metrics), cancer stage, investigations (2 metrics), outpatient attendances, inpatient admissions, major lung resections and one year survival. The primary analysis compared 2015 with 2017. Trends in metrics over the whole period were also considered. The effects of the campaign on awareness of lung cancer symptoms were evaluated using bespoke surveys. Results. There were small favourable statistically significant and clinically important changes over two years in 11 of the 15 metrics measured, including a 2.11% (95% CI 1.02-3.20: p<0.001) improvement in the percentage of lung cancers diagnosed at an early stage. However, these changes were not accompanied by increases in GP attendances. Furthermore, the time trends showed a gradual change in the metrics rather than steep changes occurring during or after the campaigns. Conclusion. There were small positive changes in most metrics relating to lung cancer diagnosis after this campaign. However, the pattern over time challenges whether the improvements are wholly attributable to the campaign. Given the importance of education on cancer in its own right, raising awareness of symptoms should remain important. However further research is needed to maximise effect on health outcomes

Parton distributions with small-x resummation:evidence for BFKL dynamics in HERA data

We present a determination of the parton distribution functions of the proton in which NLO and NNLO fixed-order calculations are supplemented by NLLx small-x resummation. Deep inelastic structure functions are computed consistently at NLO+NLLx or NNLO+NLLx, while for hadronic processes small-x resummation is included only in the PDF evolution, with kinematic cuts introduced to ensure the fitted data lie in a region where the fixed-order calculation of the hard cross-sections is reliable. In all other respects, the fits use the same methodology and are based on the same global dataset as the recent NNPDF3.1 analysis. We demonstrate that the inclusion of small-x resummation leads to a quantitative improvement in the perturbative description of the HERA inclusive and charm-production reduced cross-sections in the small x region. The impact of the resummation in our fits is greater at NNLO than at NLO, because fixed-order calculations have a perturbative instability at small x due to large logarithms that can be cured by resummation. We explore the phenomenological implications of PDF sets with small-x resummation for the longitudinal structure function $F_L$ at HERA, for parton luminosities and LHC benchmark cross-sections, for ultra-high energy neutrino-nucleus cross-sections, and for future high-energy lepton-proton colliders such as the LHeC.Comment: 70 pages, many figures. Discussion on uncertainties due to subleading logarithmic contributions. Discussion on fits with pseudodata from future high-energy lepton-proton colliders. Updated references. Version to be published in EPJ