Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis

Background: Esophageal adenocarcinoma (EA) is one of the fastest rising cancers in western countries. Barrett’s Esophagus (BE) is the premalignant precursor of EA. However, only a subset of BE patients develop EA, which complicates the clinical management in the absence of valid predictors. Genetic risk factors for BE and EA are incompletely understood. This study aimed to identify novel genetic risk factors for BE and EA.Methods: Within an international consortium of groups involved in the genetics of BE/EA, we performed the first meta-analysis of all genome-wide association studies (GWAS) available, involving 6,167 BE patients, 4,112 EA patients, and 17,159 representative controls, all of European ancestry, genotyped on Illumina high-density SNP-arrays, collected from four separate studies within North America, Europe, and Australia. Meta-analysis was conducted using the fixed-effects inverse variance-weighting approach. We used the standard genome-wide significant threshold of 5×10-8 for this study. We also conducted an association analysis following reweighting of loci using an approach that investigates annotation enrichment among the genome-wide significant loci. The entire GWAS-data set was also analyzed using bioinformatics approaches including functional annotation databases as well as gene-based and pathway-based methods in order to identify pathophysiologically relevant cellular pathways.Findings: We identified eight new associated risk loci for BE and EA, within or near the CFTR (rs17451754, P=4·8×10-10), MSRA (rs17749155, P=5·2×10-10), BLK (rs10108511, P=2·1×10-9), KHDRBS2 (rs62423175, P=3·0×10-9), TPPP/CEP72 (rs9918259, P=3·2×10-9), TMOD1 (rs7852462, P=1·5×10-8), SATB2 (rs139606545, P=2·0×10-8), and HTR3C/ABCC5 genes (rs9823696, P=1·6×10-8). A further novel risk locus at LPA (rs12207195, posteriori probability=0·925) was identified after re-weighting using significantly enriched annotations. This study thereby doubled the number of known risk loci. The strongest disease pathways identified (P<10-6) belong to muscle cell differentiation and to mesenchyme development/differentiation, which fit with current pathophysiological BE/EA concepts. To our knowledge, this study identified for the first time an EA-specific association (rs9823696, P=1·6×10-8) near HTR3C/ABCC5 which is independent of BE development (P=0·45).Interpretation: The identified disease loci and pathways reveal new insights into the etiology of BE and EA. Furthermore, the EA-specific association at HTR3C/ABCC5 may constitute a novel genetic marker for the prediction of transition from BE to EA. Mutations in CFTR, one of the new risk loci identified in this study, cause cystic fibrosis (CF), the most common recessive disorder in Europeans. Gastroesophageal reflux (GER) belongs to the phenotypic CF-spectrum and represents the main risk factor for BE/EA. Thus, the CFTR locus may trigger a common GER-mediated pathophysiology.

The large- and small-scale Ca IIK structure of the Milky Way from observations of Galactic and Magellanic sightlines

Aims. The large and small-scale (pc) structure of the Galactic interstellar medium can be investigated by utilising spectra of early-type stellar probes of known distances in the same region of the sky. This paper determines the variation in line strength of Ca ii at 3933.661 Å as a function of probe separation for a large sample of stars, including a number of sightlines in the Magellanic Clouds. 

Methods. FLAMES-GIRAFFE data taken with the Very Large Telescope towards early-type stars in 3 Galactic and 4 Magellanic open clusters in Ca ii are used to obtain the velocity, equivalent width, column density, and line width of interstellar Galactic calcium for a total of 657 stars, of which 443 are Magellanic Cloud sightlines. In each cluster there are between 43 and 111 stars observed. Additionally, FEROS and UVES Ca ii K and Na i D spectra of 21 Galactic and 154 Magellanic early-type stars are presented and combined with data from the literature to study the calcium column density - parallax relationship. 

Results. For the four Magellanic clusters studied with FLAMES, the strength of the Galactic interstellar Ca ii K equivalent width on transverse scales from ∼0.05-9 pc is found to vary by factors of ∼1.8-3.0, corresponding to column density variations of ∼0.3-0.5 dex in the optically-thin approximation. Using FLAMES, FEROS, and UVES archive spectra, the minimum and maximum reduced equivalent widths for Milky Way gas are found to lie in the range ∼35-125 mÅ and ∼30-160 mÅ for Ca ii K and Na i D, respectively. The range is consistent with a previously published simple model of the interstellar medium consisting of spherical cloudlets of filling factor ∼0.3, although other geometries are not ruled out. Finally, the derived functional form for parallax (π) and Ca ii column density (N_CaII) is found to be π(mas) = 1 / (2.39 × 10^-13 × N_CaII (cm^-2) + 0.11). Our derived parallax is ∼25 per cent lower than predicted by Megier et al. (2009, A&A, 507, 833) at a distance of ∼100 pc and ∼15 percent lower at a distance of ∼200 pc, reflecting inhomogeneity in the Ca ii distribution in the different sightlines studied.

The reliability and factorial validity of the Adolescent Alcohol Involvement Scale in a large sample in the United Kingdom

The assessment of adolescent drinking behavior is a complex task, complicated by variability in drinking patterns, the transitory and developmental nature of the behavior and the reliance (for large scale studies) on self-report questionnaires. The Adolescent Alcohol Involvement Scale (Mayer & Filstead, 1979) is a 14-item screening tool designed to help to identify alcohol misusers or more problematic drinkers. The present study utilized a large sample (n = 4066) adolescents from Northern Ireland. Results of Confirmatory Factor Analyses and reliability estimates revealed that the 14-items share sufficient common variance that scores can be considered to be reliable and that the 14 items can be scored to provide a composite alcohol use score.

Validação da Versão Portuguesa da Center for Epidemiologic Studies Depression Scale for Children (CES-DC)

A Depressão na infância e adolescência, tal como na população adulta, é uma das perturbações mentais mais comuns. Uma vez que o seu aparecimento nestas faixas etárias conduz a graves consequências na idade adulta, é fundamental identificar os sintomas depressivos precocemente. Desta forma, os instrumentos de autorrelato têm um papel fundamental, uma vez que permitem com facilidade, de forma fidedigna e válida, ter acesso a formas de pensar, sentir e agir dos sujeitos. O objetivo do presente trabalho consistiu na tradução, adaptação e estudo da Center for Epidemiological Studies Depression Scale for Children (CES-DC) (Weissman, Orvash & Padian, 1980) para os adolescentes portugueses. A amostra é constituída por 417 adolescentes, com idades compreendidas entre os 12 e os 18 anos a frequentar o 3º ciclo do ensino básio e ensino secundário. Para o estudo da validade convergente e divergente da CES-DC, foram utilizados a Depression Anxiety Stress Scales (DASS 21) (Lovibond & Lovibond, 1995), o Children's Depresssion Inventory (CID) (Marujo, 1994) e a Students' Life Satisfaction Scale (SLSS) (Marques, Pais-Ribeiro & Lopez, 2007) que avaliam, respetivamente, os estados emocionais negativos (depressão, ansiedade e stress), a sintomatologia depressiva e a satisfação global com a vida. Os resultados obtidos mostram que a escala possui uma boa consistência interna, uma estabilidade temporal adequada, assim como uma boa validade. Sugerem, ainda, tratar-se de uma escala tridimensional: fator humor, fator interpessoal e fator felicidade. Estes dados permitem o avanço da Psicologia, no que diz respeito à avaliação e prática clínica com adolescentes. A utilidade do questionário deve ser verificada noutras faixas etárias, principalmente, nas de menos de 12 anos de idade, e também numa amostra clínica. Não obstante as limitações apontadas, os resultados sugerem que a CES-DC é um questionário útil na avaliação de sintomas depressivos nos adolescentes. / Depression in children and adolescents, as well as in adults, is one of the most common mental disorders. Since its appearance in these age groups leads to serious consequences in adulthood, it is critical to identify depressive symptoms in early stages. Therefore, self-report instruments play a key role in this contexto since they allow to easily, reliably and validly have access to ways the subject thinks, feels and acts. The aim of this study was to translate, adapt and study the Center for Epidemiological Studies Depression Scale for Children (CES-DC) (Weissman, Orvash & Padian, 1980) for portuguese adolescents. The sample consists of 417 adolescents, aged between 12 and 18 years old, attending the 3rd cycle of basic education and secondary education schools. To study the convergent and divergent validity of the CES-DC, the Depression Anxiety Stress Scales (DASS 21) (Lovibond & Lovibond, 1995) was used, along with the Children's depression Inventory (CDI) (Sailor, 1994) and the Students' Life Satisfaction Scale (SLSS) (Marques, Pais-Ribeiro & Lopez, 2007) that evaluate, respectively, the negative emotional states (depression, anxiety and stress), depressive symptoms and overall satisfaction with life. The results show that the evaluated scale presents a good internal consistency, an adequate temporal stability as well as good validity. They also suggest that this is a three-dimensional scale: humor factor, interpersonal factor and happiness factor. These data allow for the progress of psychology, regarding the assessment and clinical practice among adolescents. The usefulness of the questionnaire should be verified in other age groups, especially in children with less than 12 years old and in a clinical sample. Despite these limitations, the results suggest that CES-DC is useful in the assessment questionnaire of depressive symptoms in adolescents.

A sub-kiloparsec scale view of star formation in M31

Thesis (Ph.D.)--University of Washington, 2016-08

Prosocial Behaviour in Palliative Nurses: Psychometric Evaluation of the Prosociality Scale

Aim: The aim of this study was to examine the psychometric properties of a prosociality scale within the palliative nursing context, and then examine the impact of prosocial behaviour in relation to job and educational satisfaction among palliative nurses. Methods: An online cross-sectional survey was conducted in 25 Italian palliative care centres, with a total of 107 nurses completing the prosociality scale by Caprara et al (2005). Exploratory and confirmatory factor analyses were examined to evaluate a multidimensional model of prosociality. Results: A three-factor solution with a second order factor fitted the data well. The three dimensions extracted were labelled as helping, empathy, and sharing. Participants reported high levels of prosociality. In addition, prosociality was positively associated with job and educational satisfaction. Conclusions: The prosociality scale was valid and reliable when tested with palliative nurses. Although prosociality may be embedded in nurses’ personalities, this quality should be actively promoted to expand and improve the culture and the ethics of nursing.

Quantifying Barriers to Meditation as a Health Behavior: Exploratory and Confirmatory Factor Analysis of the Determinants of Meditation Practice Inventory

Although the benefits of mindfulness meditation practices have been widely documented, research data suggest that there are barriers to regularly engaging in meditation behavior. In order to explore research questions pertaining to meditation initiation and adherence, psychometrically valid scales to assess barriers to meditation practice are necessary. The aim of the present study was to explore the factor structure and construct validity of the Determinants of Meditation Practice Inventory (DMPI) (Williams et al., 2011), a perceived barriers to meditation scale. Exploratory and confirmatory factor analyses along with construct validity tests were performed on data obtained from two large, community samples. Results supported the DMPI as a valid scale assessing perceived barriers with four factors, Lack of Interest, Knowledge Concerns, Pragmatic Concerns and Sociocultural Beliefs. The present study offers a DMPI-revised scale that may be reliably used to assess attitudes and beliefs that might impede meditation behavior.

Small scale turbulence and mixing in semi-enclosed seas (Persian Gulf)

Turbulence and internal waves are probably important in generating layered structures in frontal region of marine environments (e.g. near river plumes outflow into the sea). Here we investigate the role of normal modes of internal waves in generation of layered structure in a part of Persian Gulf where river plume inters and in some laboratory experiments. The model prediction and observations show that layers so formed have a thickness of about 2m based on salinity variations with depth, but layers (about 5m) based on horizontal velocity profiles. Laboratory experiments with a plume outflow in a Filling Box profile also generate normal mode layered structure with 21H=0.5 (where A is layer thickness and H is the plume depth). In these experiments as Re of the flow is smaller than the Re of field flow. The normal modes are substantially dissipated with depth. Typical values of dissipation factor is about 0(100). This factor for field observation is 0(10) which is still substantial. Qualitative comparison between layered structure in field and laboratory is good. It should be emphasized that field observation is for semi-enclosed seas but the laboratory experiments are for enclosed region. Hence some of the discrepancies in the results of two cases are inevitable. Layered structures in marine environments are also produced by double diffusive convection. In this region this should be studied separately.

The psychometric properties of the brief Other as Shamer Scale for Children (OAS‐C) : preliminary validation studies in a sample of Portuguese children

Shame is a social emotion with adaptive functions involved in human be-havior and social interactions. This emotion is regarded as an involuntary response associated with increased self-awareness, loss of status and self-devaluation (Gilbert, 1998), that may render individuals more prone to psychopathology (Gilbert, 1998; Pinto-Gouveia & Matos, 2011). Thus, identifying and assessing feelings of shame in childhood is essential in addressing the actual impact of shame on individual’s developmental trajectory. The Other As Shamer Scale (OAS; Goss, Gilbert & Allan, 1994) is a widely used measure of external shame, adapted and translated to several languages — including Portuguese (Matos, Pinto-Gouveia, Gilbert, Duarte & Figueiredo, 2015) — to adult and to adolescent populations (OASB-A - Other As Shamer Brief for adolescents; translated and adapted by Cunha, Xavier, Cherpe & Pinto-Gouveia, 2014). The current study aims to adapt and to explore the psychometric proper-ties of the brief OAS in a sample of Portuguese children attending to elementary schools.

Adaptation and validation into Portuguese language of the HIV Antibody Testing Attitude Scale

Objective. To culturally adapt and validate a version in European Portuguese language of the HIV Antibody Testing Attitude Scale. Methods. Study conducting a methodological investigation for the adaptation and validation of an attitude measurement instrument. The instrument translation and back-translation were performed. Then, a pre-test was conducted. The study used a sample of 317 subjects from the academic community - students, professors and other professionals - who were contacted in the campus. Ethical principles were observed. Results. Three analyses were conducted using the method of principal component analysis (PCA) with five, four and three factors. A three-factor solution was achieved, which presents 50.82% variance. In the analysis of inter-item correlation, values between -0.018 and 0.749 were observed. Internal consistency shows Cronbach’s alpha coefficients of 0.860 overall and between 0.865 and 0.659 in the three factors. Conclusion. The instrument version shows psychometric properties that allow its use in Portuguese-speaking countries.

Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem Cell Trial of Recovery EnhanceMent After Stroke (STEMS) Pilot Randomized, Controlled Trial (ISRCTN 16784092)

Background and Purpose - Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony-stimulating factor (G-CSF) after stroke and its effect on circulating CD34 stem cells. Methods - We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 g/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34 stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment. Results - Thirty-six patients, whose mean SD age was 768 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 g/kg) increased CD34 count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, P0.005). A dose-dependent rise in white cell count (P0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days. Conclusions - ”G-CSF is effective at mobilizing bone marrow CD34 stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined. (Stroke. 2006;37:2979-2983.)

On Growth Rate of Wind Waves: Impact of Short-Scale Breaking Modulations

The wave generation model based on the rapid distortion concept significantly underestimates empirical values of the wave growth rate. As suggested before, inclusion of the aerodynamic roughness modulations effect on the amplitude of the slope-correlated surface pressure could potentially reconcile this model approach with observations. This study explores the role of short-scale breaking modulations to amplify the growth rate of modulating longer waves. As developed, airflow separations from modulated breaking waves result in strong modulations of the turbulent stress in the inner region of the modulating waves. In turn, this leads to amplifying the slope-correlated surface pressure anomalies. As evaluated, such a mechanism can be very efficient for enhancing the wind-wave growth rate by a factor of 2-3.

Measuring attachment to life in old age: the Portuguese version of the Positive Valuation of Life Scale (Positive VOL)

Purpose This study aims to present the psychometric properties of the Portuguese version of the Positive Valuation of Life Scale (Lawton et al. in J Aging Ment Healt 13:3–31, 2001). Method Sample included 207 community-dwelling elders (129 women; MAge = 77.2 years, SD = 7.5). The data collection included the translated and adapted Portuguese version of Positive Valuation of Life Scale, Life Satisfac- tion Index Z, Meaning in Life Questionnaire and Geriatric Depression Scale. Results From exploratory factor analysis, two factors emerged, existential beliefs and perceived control, ex- plaining 49 % of the total variance. Both factors were positively related with meaning in life and life satisfaction and negatively related with depression (p\0.05). The values obtained for internal consistency for the total scale and for each subscale were good (a [ 0.75). Conclusion The Portuguese version of Positive VOL Scale represents a reliable and valid measure to capture the subjective experience of attachment to one’s life. The two-factor structure is an update to Lawton’s previous work and in line with findings obtained in the USA (Dennis et al. in What is valuation of life for frail community-dwelling older adults: factor structure and criterion validity of the VOL, Thomas Jefferson University, Center for Applied Research on Aging and Health Research, 2005) and Japan (Nakagawa et al. in Shinrigaku Kenkyu 84:37–46, 2013). Future research is required to investigate VOL predictors and the potential changes toward the end of the life span.

The Warwick-Edinburgh Mental Well-Being Scale

Background There is increasing international interest in the concept of mental well-being and its contribution to all aspects of human life. Demand for instruments to monitor mental well-being at a population level and evaluate mental health promotion initiatives is growing. This article describes the development and validation of a new scale, comprised only of positively worded items relating to different aspects of positive mental health: the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). Methods WEMWBS was developed by an expert panel drawing on current academic literature, qualitative research with focus groups, and psychometric testing of an existing scale. It was validated on a student and representative population sample. Content validity was assessed by reviewing the frequency of complete responses and the distribution of responses to each item. Confirmatory factor analysis was used to test the hypothesis that the scale measured a single construct. Internal consistency was assessed using Cronbach’s alpha. Criterion validity was explored in terms of correlations between WEMWBS and other scales and by testing whether the scale discriminated between population groups in line with pre-specified hypotheses. Test-retest reliability was assessed at one week using intra-class correlation coefficients. Susceptibility to bias was measured using the Balanced Inventory of Desired Responding. Results WEMWBS showed good content validity. Confirmatory factor analysis supported the single factor hypothesis. A Cronbach’s alpha score of 0.89 (student sample) and 0.91 (population sample) suggests some item redundancy in the scale. WEMWBS showed high correlations with other mental health and well-being scales and lower correlations with scales measuring overall health. Its distribution was near normal and the scale did not show ceiling effects in a population sample. It discriminated between population groups in a way that is largely consistent with the results of other population surveys. Test–retest reliability at one week was high (0.83). Social desirability bias was lower or similar to that of other comparable scales. Conclusions WEMWBS is a measure of mental well-being focusing entirely on positive aspects of mental health. As a short and psychometrically robust scale, with no ceiling effects in a population sample, it offers promise as a tool for monitoring mental well-being at a population level. Whilst WEMWBS should appeal to those evaluating mental health promotion initiatives, it is important that the scale’s sensitivity to change is established before it is recommended in this context.

Validation of the Flexibility of Responses to Self-Critical Thoughts Scale (FoReST) in a clinical population

Background: The Flexibility of Responses to Self-Critical Thoughts Scale (FoReST) is a questionnaire that was developed to assess whether people can be psychologically flexible when experiencing critical thoughts about themselves. This measure could have important application for evaluating third wave therapies such as Acceptance and Commitment Therapy (ACT) and Compassion Focused therapy (CFT). This study investigated the validity (concurrent, predictive and incremental), internal consistency and factor structure of the FoReST in a sample of people experiencing mental health difficulties. Method: A total of 132 individuals attending Primary Care and Community Mental Health Teams within NHS Greater Glasgow and Clyde (NHS GGC) and Psychological Therapy Teams within NHS Lanarkshire participated in this study. Participants completed a battery of assessments that included the FoReST and related measures of similar constructs (psychological flexibility, self-compassion and self-criticism) and measures of mental health and well-being. A cross-sectional correlational design was used. Results: An Exploratory factor analysis described an interpretable 2-factor structure within the items of the FoReST: unworkable action and experiential avoidance. The FoReST demonstrated good internal consistency ( = .89). Concurrent validity was supported through moderate to strong correlations with similar measures and moderate correlations with other mental health and well-being outcomes. Conclusions: The FoReST appears to be a valid assessment measure for using with individuals experiencing mental health difficulties. This new measure will be of use for practitioners using ACT, CFT and those integrating both, to help monitor the process of change in flexibility and self-critical thinking across therapy. Further longitudinal studies are required to assess the test-retest reliability of the FoReST.