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BACKGROUND: The International Trauma Questionnaire-Child and Adolescent version (ITQ-CA) is a self-report measure that assesses posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) based on the diagnostic formulation of the 11th version of the International Classification of Diseases (ICD-11). This study aimed to provide a Chinese translation and psychometric evaluation of the ITQ-CA using a sample of mental-health service seeking adolescents in Mainland China. METHODS: The ITQ-CA was translated and back-translated from English to simplified Chinese and finalized with consensus from an expert panel. Adolescents ages 12-17 were recruited via convenience sampling from an outpatient psychiatric clinic in Mainland China. Participants completed the ITQ-CA; measures of four criterion variables (depression, anxiety, stress, adverse childhood experiences); and the PTSD Checklist for DSM-5 (PCL-5). Construct validity, concurrent validity, and comparison of PTSD caseness between ICD-11 and DSM-5 measures were assessed. RESULTS: The final sample consisted of 111 Chinese adolescents (78% female; mean age of 15.23), all diagnosed with a major depressive disorder. Confirmatory factor analysis indicated the two-factor second-order model provided optimal fit. All criterion variables were positively and significant correlated with the six ITQ-CA symptom cluster summed scores. In the present sample, 69 participants (62.16%) met symptom criteria for ICD-PTSD or CPTSD using the ITQ-CA, and 73 participants (65.77%) met caseness for DSM-5 PTSD using the PCL-5. Rates of PTSD symptom cluster endorsement and caseness deriving from both diagnostic systems were comparable. CONCLUSIONS: The Chinese ITQ-CA has acceptable psychometric properties and confers additional benefits in identifying complex presentations of trauma-related responses in younger people seeking mental health services.
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AIMS: To assess the factorial validity and internal reliability of the International Trauma Questionnaire (ITQ) among a treatment-seeking sample of survivors of sexual violence in Ireland. In addition, to assess the diagnostic rate of post-traumatic stress disorder (PTSD) and complex post-traumatic stress disorder (CPTSD) among the samples. METHODS: Participants were adult survivors of sexual violence (N = 114) in receipt of therapeutic support at the Dublin Rape Crisis Centre. The ITQ was utilised to measure PTSD and CPTSD symptoms and confirmatory factor analysis was employed to assess the factorial validity of the ITQ. Composite reliability was employed to assess the internal reliability of the ITQ scale scores. RESULTS: The confirmatory factor analysis results indicated that a six-factor correlated model and a two-factor higher model were good representations of the latent structure of the ITQ, both models are consistent with the conceptualisation of CPTSD. All ITQ subscales possessed satisfactory internal reliability except for the affective dysregulation subscale. Of the sample, 56.1% met the criteria for CPTSD and 20.2% met the criteria for PTSD. CONCLUSIONS: The ITQ captured a distinction between PTSD and CPTSD symptoms and produced reliable scores within the sample, but replication with a larger sample size is required. In addition, the study findings demonstrated that CPTSD was relatively common among those seeking psychological support following sexual violence.
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Delitos Sexuales , Trastornos por Estrés Postraumático , Adulto , Humanos , Clasificación Internacional de Enfermedades , Irlanda/epidemiología , Reproducibilidad de los Resultados , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Encuestas y Cuestionarios , SobrevivientesRESUMEN
OBJECTIVES: Hesitance and resistance to COVID-19 vaccination poses a serious challenge to achieving adequate vaccine uptake in the general population. Cross-sectional data from the early months of the pandemic indicates that approximately one-third of adults in multiple nations are hesitant or resistant to a vaccine for COVID-19. Using longitudinal data, we tracked changes in attitudes to COVID-19 vaccination during the pandemic. STUDY DESIGN: This is a quantitative, longitudinal design. METHOD: Nationally representative samples of the adult general population of the Republic of Ireland (N = 1041) and the United Kingdom (N = 2025) were assessed for their attitudes towards COVID-19 vaccination at three points from March to August 2020. RESULTS: Statistically significant increases in resistance to COVID-19 vaccination were observed in Irish (from 9.5% to 18.1%) and British (from 6.2% to 10%) adults. CONCLUSION: Resistance to vaccination has significantly increased in two European nations as the pandemic has progressed. Growing resistance to COVID-19 vaccination will pose a challenge to public health officials responsible for ensuring sufficient vaccine coverage.
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Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Pandemias/prevención & control , Negativa a la Vacunación , Vacunación/psicología , Adulto , Estudios Transversales , Etnicidad , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Salud Pública , SARS-CoV-2 , Reino UnidoRESUMEN
BACKGROUND: The COVID-19 pandemic in Ireland resulted in a nationwide quarantine on March 27, 2020. This study represents the first assessment of rates of anxiety and depression in the general population of Ireland during the pandemic. AIMS: Our first aim was to estimate the probable prevalence rates of generalized anxiety disorder (GAD) and depression and to identify sociodemographic risk factors associated with screening positive for GAD or depression. Our second aim was to determine if COVID-19 related anxiety was highest amongst those in society at greatest risk of morality from COVID-19. METHOD: Self-report data were collected from a nationally representative Irish sample (N = 1041) online between March 31 and April 5; the first week of the nationwide quarantine measures. Recognized cut-off scores on the GAD-7 and PHQ-9 were used to estimate rates of GAD and depression. Correlates of screening positive for GAD or depression were assessed using logistic regression analysis. RESULTS: GAD (20.0%), depression (22.8%) and GAD or depression (27.7%) was common. Screening positive for GAD or depression was associated with younger age, female sex, loss of income due to COVID-19, COVID-19 infection and higher perceived risk of COVID-19 infection. Citizens aged 65 and older had significantly higher levels of COVID-19 related anxiety than adults aged 18-34. CONCLUSIONS: Initial results from this multi-wave study monitoring changes in population anxiety and depression throughout the pandemic indicate that GAD and depression were common experiences in the population during the initial phase of the COVID-19 pandemic.
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Ansiedad/epidemiología , COVID-19/epidemiología , Depresión/epidemiología , Cuarentena/estadística & datos numéricos , Estrés Psicológico/epidemiología , Adulto , Anciano , Comorbilidad , Femenino , Humanos , Irlanda , Masculino , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Prevalencia , Cuarentena/psicología , Factores de RiesgoRESUMEN
BACKGROUND: Adjustment disorder (AjD) is one of the most frequently used diagnoses in psychiatry but a diagnostic definition for AjD was only introduced in release of the ICD-11. This study sought to develop and validate a new measure operationalizing the ICD-11's narrative description of AjD, and to determine the current rate of people meeting the symptoms indicative of AjD in the general population of the Republic of Ireland. METHODS: The International Adjustment Disorder Questionnaire (IADQ) was constructed to measure the core diagnostic criteria of ICD-11 AjD: stressor exposure, preoccupations with, and failure to adapt to, the stressor, timing of symptom onset, and functional impairment. A nationally representative sample (N = 1,020) of adults from Ireland completed the IADQ. RESULTS: Confirmatory factor analysis supported construct validity and the reliability estimates were excellent. The IADQ correlated strongly with depression, anxiety, and posttraumatic stress. The criteria were met by 7.0% of the sample, adjusted for other exclusionary disorders. DISCUSSION: The IADQ is a measure based on the ICD-11's description and produces reliable scores, however it should not be used for clinical assessment until validated with clinical interviews.
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Trastornos de Adaptación/diagnóstico , Clasificación Internacional de Enfermedades , Encuestas y Cuestionarios , Trastornos de Adaptación/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis Factorial , Femenino , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
INTRODUCTION: Adverse childhood experiences (ACEs) constitute a significant global mental health burden. Prior studies typically investigated the impact of ACEs on mental health using a cumulative risk approach; most ACEs studies were also conducted in Western settings. PURPOSE: This study aimed to examine ACEs using a pattern-based approach and assess their associations with mental health outcomes by early adulthood in East Asia. METHODS: The present study included measures of exposure to 13 categories of ACEs, depression, anxiety, maladjustment, and posttraumatic stress in a sample of 1346 university students from Hong Kong, China, Taiwan, and Japan. RESULTS: Latent class analysis indicated three distinct patterns of ACE exposure: Class 1: Low ACEs (76.0%); Class 2: Household Violence (20.6%); and Class 3: Household Dysfunction (3.4%). Those representing Class 3 had significantly more ACEs compared with those in Classes 1 or 2. Controlling for age and sex, those in Class 2 reported significantly higher depression and maladjustment symptoms compared with those in Class 1; both Classes 2 and 3 had significantly higher anxiety symptoms and odds for meeting diagnostic criteria for posttraumatic stress disorders compared with those in Class 1. CONCLUSIONS: Study findings suggest that young adults' mental health, at least under certain contexts, is more closely linked with the nature and pattern of ACE co-occurrence, rather than the number of ACEs.
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Experiencias Adversas de la Infancia , Salud Mental , Estudiantes , Adolescente , China , Depresión , Femenino , Hong Kong , Humanos , Japón , Masculino , Trastornos Mentales , Estudiantes/psicología , Encuestas y Cuestionarios , Taiwán , Universidades , Violencia , Adulto JovenRESUMEN
OBJECTIVE: Support for ICD-11 post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD) is growing; however, few studies include refugees or examine the clinical utility of PTSD/CPTSD classifications. This study sought to provide the first evaluations of (i) the factor structure of ICD-11 PTSD/CPTSD amongst refugees in the Middle East; and (ii) the clinical utility of the International Trauma Questionnaire (ITQ) to identify PTSD/CPTSD in a humanitarian context. METHOD: Participants were 112 treatment-seeking Syrian refugees living in Lebanon. Factorial validity was assessed using confirmatory factor analysis (CFA) based on responses to the ITQ. Clinical utility of the ITQ was assessed through semi-structured interviews with six Lebanese psychotherapists. RESULTS: Complex PTSD (36.1%) was more common than PTSD (25.2%), and no sex or age differences were observed at the prevalence or symptomatic levels. CFA results supported a two-factor higher-order model consistent with ICD-11 PTSD/CPTSD. Qualitative findings indicated that the ITQ is generally positively regarded, with some limitations and suggested modifications noted. CONCLUSION: This is the first study to support the ICD-11 PTSD/CPTSD amongst refugees in the Middle East and the clinical utility of the ITQ in a humanitarian context. Findings support the growing evidence for the cross-cultural applicability of ICD-11 PTSD/CPTSD.
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Clasificación Internacional de Enfermedades , Escalas de Valoración Psiquiátrica/normas , Trauma Psicológico/diagnóstico , Refugiados , Trastornos por Estrés Postraumático/diagnóstico , Adolescente , Adulto , Análisis Factorial , Femenino , Humanos , Líbano , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Siria , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to finalize the development of the International Trauma Questionnaire (ITQ), a self-report diagnostic measure of post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD), as defined in the 11th version of the International Classification of Diseases (ICD-11). METHOD: The optimal symptom indicators of PTSD and CPTSD were identified by applying item response theory (IRT) analysis to data from a trauma-exposed community sample (n = 1051) and a trauma-exposed clinical sample (n = 247) from the United Kingdom. The validity of the optimized 12-item ITQ was assessed with confirmatory factor analyses. Diagnostic rates were estimated and compared to previous validation studies. RESULTS: The latent structure of the 12-item, optimized ITQ was consistent with prior findings, and diagnostic rates of PTSD and CPTSD were in line with previous estimates. CONCLUSION: The ITQ is a brief, simply worded measure of the core features of PTSD and CPTSD. It is consistent with the organizing principles of the ICD-11 to maximize clinical utility and international applicability through a focus on a limited but central set of symptoms. The measure is freely available and can be found in the body of this paper.
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Clasificación Internacional de Enfermedades , Escalas de Valoración Psiquiátrica/normas , Trauma Psicológico/diagnóstico , Autoinforme/normas , Trastornos por Estrés Postraumático/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Reino Unido , Adulto JovenRESUMEN
BACKGROUND: The World Health Organization will publish its 11th revision of the International Classification of Diseases (ICD-11) in 2018. The ICD-11 will include a refined model of posttraumatic stress disorder (PTSD) and a new diagnosis of complex PTSD (CPTSD). Whereas emerging data supports the validity of these proposals, the discriminant validity of PTSD and CPTSD have yet to be tested amongst a sample of refugees. METHODS: Treatment-seeking Syrian refugees (N = 110) living in Lebanon completed an Arabic version of the International Trauma Questionnaire; a measure specifically designed to capture the symptom content of ICD-11 PTSD and CPTSD. RESULTS: In total, 62.6% of the sample met the diagnostic criteria for PTSD or CPTSD. More refugees met the criteria for CPTSD (36.1%) than PTSD (25.2%) and no gender differences were observed. Latent class analysis results identified three distinct groups: (1) a PTSD class, (2) a CPTSD class and (3) a low symptom class. Class membership was significantly predicted by levels of functional impairment. CONCLUSION: Support for the discriminant validity of ICD-11 PTSD and CPTSD was observed for the first time within a sample of refugees. In support of the cross-cultural validity of the ICD-11 proposals, the prevalence of PTSD and CPTSD were similar to those observed in culturally distinct contexts.
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This study investigated how both caregiver and patient factors predict different aspects of burden in colorectal cancer caregivers. One hundred and fifty-three caregiver-survivor dyads separately provided information on patient disease and treatment-related factors, and perceived global health status (EORTC QLQ30), along with caregiver socio-demographic factors, health and care-related activities. Four multiple regression analyses were conducted to assess the influence of caregiver characteristics, patient characteristics and care-related activities on four dimensions of burden from the Caregiver Reaction Assessment scale. Caregiver characteristics significantly predicted health and financial burden (11%-13% of explained variance) with comorbidity and younger age increasing this risk. Patient health, in particular global health status and the presence of a stoma, predicted all burden scores, explaining 14%-22% of variance. Care-related activities was also a significant predictor of all burden scores, explaining an additional 5%-11% of variance, with time involved in caring the most consistent predictor. Results highlight that a combination of factors influence caregiver burden. These results may be used to identify those most at risk, allowing practitioners to deliver tailored effective support. In particular, efforts to alleviate the burden of caring on caregiver schedule may be merited, given that this was the domain in which the burden was greatest.
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Cuidadores/economía , Neoplasias Colorrectales/economía , Costo de Enfermedad , Adulto , Anciano , Supervivientes de Cáncer/psicología , Cuidadores/psicología , Salud de la Familia/economía , Femenino , Gastos en Salud , Estado de Salud , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Calidad de Vida/psicología , Análisis de Regresión , Apoyo Social , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Recently, the American Psychiatric Association (DSM-5) and the World Health Organization (ICD-11) have both revised their formulation of post-traumatic stress disorder (PTSD). The primary aim of this study was to compare DSM-5 and ICD-11 PTSD prevalence and comorbidity rates, as well as the level of disability associated with each diagnosis. METHOD: This study was based on a representative sample of adult Ukrainian internally displaced persons (IDPs: N = 2203). Post-traumatic stress disorder prevalence was assessed using the PTSD Checklist for DSM-5 and the International Trauma Questionnaire (ICD-11). Anxiety and depression were measured using the Generalized Anxiety Disorder Scale and the Patient Health Questionnaire-Depression. Disability was measured using the WHO Disability Assessment Schedule 2.0. RESULTS: The prevalence of DSM-5 PTSD (27.4%) was significantly higher than ICD-11 PTSD (21.0%), and PTSD rates for females were significantly higher using both criteria. ICD-11 PTSD was associated with significantly higher levels of disability and comorbidity. CONCLUSION: The ICD-11 diagnosis of PTSD appears to be particularly well suited to identifying those with clinically relevant levels of disability.
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Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Personas con Discapacidad/estadística & datos numéricos , Clasificación Internacional de Enfermedades , Acontecimientos que Cambian la Vida , Trauma Psicológico/epidemiología , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Adulto , Comorbilidad , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Autoinforme , Factores Sexuales , Ucrania/epidemiologíaRESUMEN
The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Internacionalidad , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Detección Precoz del Cáncer , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Humanos , Factores de RiesgoRESUMEN
OBJECTIVE: The 11th version of the International Classification of Diseases (ICD-11) has proposed two related trauma diagnoses: Post-traumatic stress disorder (PTSD) and Complex PTSD (CPTSD). Using a newly developed, disorder-specific measure of PTSD and CPTSD called the International Trauma Questionnaire (ITQ) the current study will (i) assess the factorial validity of ICD-11 PTSD and CPTSD; (ii) provide the first test of the discriminant validity of these constructs; and (iii) provide the first comparison of ICD-11, and Diagnostic and Statistical Manual, Fifth Edition (DSM-5), PTSD diagnostic rates using disorder-specific measures. METHOD: ICD-11 and DSM-5 PTSD-specific measures were completed by a British clinical sample of trauma-exposed patients (N = 171). The structure and validity of ICD-11 PTSD and CPTSD were assessed by means of factor analysis and assessing relationships with criterion variables. RESULTS: Diagnostic rates under ICD-11 were significantly lower than those under DSM-5. A two-factor second-order model reflecting the distinction between PTSD and CPTSD best represented the data from the ITQ; and the PTSD and CPTSD factors differentially predicted multiple psychological variables. CONCLUSION: The factorial and discriminant validity of ICD-11 PTSD and CPTSD was supported, and ICD-11 produces fewer diagnostic cases than DSM-5.
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Manual Diagnóstico y Estadístico de los Trastornos Mentales , Clasificación Internacional de Enfermedades , Escalas de Valoración Psiquiátrica , Trauma Psicológico/diagnóstico , Trastornos por Estrés Postraumático/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Previously, we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone-binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study. Free testosterone, free DHT, and free estradiol were estimated using standard formulas. Multivariable logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) of associations between exposures and Barrett's esophagus. While plasma hormone and sex hormone-binding globulin concentrations were not associated with all cases of Barrett's esophagus, we did observe positive associations with estrogens in younger men (e.g. estrone + estradiol ORcontinuous per ½IQR = 2.92, 95%CI:1.08, 7.89), and free androgens in men with higher waist-to-hip ratios (e.g. free testosterone ORcontinuous per ½IQR = 2.71, 95%CI:1.06, 6.92). Stratification by body mass index, antireflux medications, and geographic location did not materially affect the results. This study found evidence for associations between circulating sex steroid hormones and Barrett's esophagus in younger men and men with higher waist-to-hip ratios. Further studies are necessary to elucidate whether sex steroid hormones are consistently associated with esophageal adenocarcinogenesis.
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Esófago de Barrett/sangre , Dihidrotestosterona/sangre , Estradiol/sangre , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangre , Factores de Edad , Anciano , Índice de Masa Corporal , Ensayo de Inmunoadsorción Enzimática , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: Although there is emerging evidence for the factorial validity of the distinction between post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD) proposed in ICD-11, such evidence has been predominantly based on using selected items from individual scales that describe these factors. We have attempted to address this gap in the literature by testing a range of alternative models of disorders of traumatic stress using a broader range of symptoms and standardized measures. METHOD: Participants in this cross-sectional study were a sample of individuals who were referred for psychological therapy to a National Health Service (NHS) trauma centre in Scotland (N = 195). Participants were recruited over a period of 18 months and completed measures of stressful life events, DSM-5 PTSD, emotion dysregulation, self-esteem and interpersonal difficulties. RESULTS: Overall, results indicate that a structural model incorporating six first-order factors (re-experiencing, avoidance of traumatic reminders, sense of threat, affective dysregulation, negative self-concept and disturbances in relationships) and two second-order factors (PTSD and disturbances in self-organization [DSO]) was the best fitting. The model presented with good concurrent validity. Childhood trauma was found to be more strongly associated with DSO than with PTSD. CONCLUSION: Our results are in support of the ICD-11 proposals for PTSD and CPTSD.
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Trastornos por Estrés Postraumático/psicología , Estudios Transversales , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Acontecimientos que Cambian la Vida , Masculino , Modelos Psicológicos , Escalas de Valoración PsiquiátricaRESUMEN
Gravitational lensing due to the large-scale distribution of matter in the cosmos distorts the primordial cosmic microwave background (CMB) and thereby induces new, small-scale B-mode polarization. This signal carries detailed information about the distribution of all the gravitating matter between the observer and CMB last scattering surface. We report the first direct evidence for polarization lensing based on purely CMB information, from using the four-point correlations of even- and odd-parity E- and B-mode polarization mapped over â¼30 square degrees of the sky measured by the POLARBEAR experiment. These data were analyzed using a blind analysis framework and checked for spurious systematic contamination using null tests and simulations. Evidence for the signal of polarization lensing and lensing B modes is found at 4.2σ (stat+sys) significance. The amplitude of matter fluctuations is measured with a precision of 27%, and is found to be consistent with the Lambda cold dark matter cosmological model. This measurement demonstrates a new technique, capable of mapping all gravitating matter in the Universe, sensitive to the sum of neutrino masses, and essential for cleaning the lensing B-mode signal in searches for primordial gravitational waves.
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We reconstruct the gravitational lensing convergence signal from cosmic microwave background (CMB) polarization data taken by the Polarbear experiment and cross-correlate it with cosmic infrared background maps from the Herschel satellite. From the cross spectra, we obtain evidence for gravitational lensing of the CMB polarization at a statistical significance of 4.0σ and indication of the presence of a lensing B-mode signal at a significance of 2.3σ. We demonstrate that our results are not biased by instrumental and astrophysical systematic errors by performing null tests, checks with simulated and real data, and analytical calculations. This measurement of polarization lensing, made via the robust cross-correlation channel, not only reinforces POLARBEAR auto-correlation measurements, but also represents one of the early steps towards establishing CMB polarization lensing as a powerful new probe of cosmology and astrophysics.
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We characterized Fas immunoreactivity, functionality and its role in the response to mitomycin-C (MMC) chemotherapy in vitro in cell lines and in vivo in bladder washings from 23 transitional cell carcinoma of the bladder (TCCB) patients, harvested prior to and during MMC intravesical treatment. Having established the importance of functional Fas, we investigated the methylation and exon 9 mutation as mechanisms of Fas silencing in TCCB. For the first time, we report p53 up-regulation in 9/14 and Fas up-regulation in 7/9 TCCB patients during intravesical MMC treatment. Fas immunoreactivity was strong in the TCCB cell line T24 and in 17/20 (85%) tumor samples from patients with advanced TCCB. T24 and HT1376 cells were resistant to MMC and recombinant Fas ligand, whilst RT4 cells were responsive to Fas ligand and MMC. Using RT4 cells as a model, siRNA targeting p53 significantly reduced MMC-induced p53 and Fas up-regulation and stable DN-FADD transfection decreased MMC-induced apoptosis, suggesting that functional Fas enhances chemotherapy responses in a p53-dependent manner. In HT1376 cells, 5-aza-2-deoxycytidine (12 µM) induced Fas immunoreactivity and reversed methylation at CpG site -548 within the Fas promoter. This site was methylated in 13/24 (54%) TCCB patient samples assessed using Methylation-Specific Polymerase Chain Reaction. There was no methylation at either the p53 enhancer region within the first intron or at the SP-1 binding region in the promoter and no mutation within exon 9 in tumor DNA extracted from 38 patients. Methylation at CpG site -548 is a potential target for demethylating drugs.