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Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment1-3. Because it is grounded below sea level4,5, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean6,7. Recent ice-flow acceleration2,8 and retreat of the ice front8-10 and GL11,12 indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice-ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming.
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OBJECTIVE: The goal of this practice statement is to help members and their multidisciplinary teams recognize infusion reactions and hypersensitivity reactions in the clinical setting. It will provide recommendations to help guide response to reactions and desensitization when appropriate, to promote safe use of chemotherapeutic agents among all providers in the delivery process. METHODS: A multi-disciplinary team of healthcare professionals from the Society of Gynecologic Oncology Education Committee collaborated to review peer reviewed literature and guidelines to develop a practice statement on the management of chemotherapy hypersensitivity reactions and desensitization regimens. RESULTS: There is always potential for a patient to have a reaction to any medication, with both infusion reactions and hypersensitivity reactions potentially occurring in the treatment of gynecologic cancers. Premedication to prevent reactions should be given at least prior to infusion for regimens that include the most common agents associated with reactions. At the time when reaction is occurring it might be difficult to distinguish between an infusion reaction versus true hypersensitivity given the similarities in signs and symptoms, therefore it is important that orders to manage reactions be included in every chemotherapy order set so the infusion nurse can provide immediate interventions while waiting for the provider to arrive to assess the patient. Desensitization is a potential option to allow the patient to continue to receive the offending agent. While a variety of desensitization regimens have been presented in the literature, the goal is to minimize steps and variability to decrease opportunity for errors during chemotherapy preparation or administration. CONCLUSION: Incorporating a review of the literature and clinical experience from the SGO Education Committee, this paper provides an overview of current approaches for prevention and management of reactions to commonly used chemotherapy agents for gynecologic cancers.
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The West Antarctic Ice Sheet is one of the largest potential sources of rising sea levels. Over the past 40 years, glaciers flowing into the Amundsen Sea sector of the ice sheet have thinned at an accelerating rate, and several numerical models suggest that unstable and irreversible retreat of the grounding line-which marks the boundary between grounded ice and floating ice shelf-is underway. Understanding this recent retreat requires a detailed knowledge of grounding-line history, but the locations of the grounding line before the advent of satellite monitoring in the 1990s are poorly dated. In particular, a history of grounding-line retreat is required to understand the relative roles of contemporaneous ocean-forced change and of ongoing glacier response to an earlier perturbation in driving ice-sheet loss. Here we show that the present thinning and retreat of Pine Island Glacier in West Antarctica is part of a climatically forced trend that was triggered in the 1940s. Our conclusions arise from analysis of sediment cores recovered beneath the floating Pine Island Glacier ice shelf, and constrain the date at which the grounding line retreated from a prominent seafloor ridge. We find that incursion of marine water beyond the crest of this ridge, forming an ocean cavity beneath the ice shelf, occurred in 1945 (±12 years); final ungrounding of the ice shelf from the ridge occurred in 1970 (±4 years). The initial opening of this ocean cavity followed a period of strong warming of West Antarctica, associated with El Niño activity. Thus our results suggest that, even when climate forcing weakened, ice-sheet retreat continued.
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This corrects the article DOI: 10.1038/nature20136.
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OBJECTIVES: 'Overweight and obesity' is the second biggest preventable cause of cancer after smoking. In 2018, Cancer Research UK launched an awareness raising campaign about the link between overweight and obesity and cancer risk. This study aimed to evaluate the reach and impact of the campaign. STUDY DESIGN: This study was a repeated cross-sectional online survey. METHODS: The campaign consisted of six elements including the main message that 'Obesity is a cause of cancer'. UK adults and Members of Parliament (MPs) were surveyed before the campaign (W1; n = 2124 and n = 151), 1 month (W2; n = 2050 and n = 151) and 3 months after the campaign (W3; n = 2059 and MPs not surveyed). Outcome measures were campaign reach, awareness of overweight and obesity as risk factors for cancer, attitudes towards individuals who are overweight or obese, support for policies to reduce obesity and reactions to the campaign. RESULTS: Overall, 76.2% of MPs and just under half of the public (47.5% in W2 and 36.8% in W3) reported having seen the campaign. Unprompted awareness of obesity as a risk factor increased among the public from 17.1% at W1 to 43.3% in W2 (odds ratio 3.71, 95% confidence interval 3.18-4.33) and 30.3% in W3 (odds ratio 2.11, 95% confidence interval 1.80-2.47). A similar pattern was seen for prompted awareness and among MPs. There were no consistent changes in attitudes towards overweight individuals or support for policies to reduce obesity. CONCLUSIONS: This evaluation suggests that the campaign achieved the primary objective of increasing awareness of the link between obesity and cancer without increasing negative attitudes towards individuals who are overweight or obese.
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Neoplasias , Sobrepeso , Adulto , Humanos , Estudios Transversales , Obesidad/complicaciones , Obesidad/epidemiología , Neoplasias/epidemiología , Neoplasias/etiología , Neoplasias/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Reino Unido/epidemiología , Promoción de la SaludRESUMEN
PURPOSE: Gastro-oesophageal reflux disease (GORD) is commonly thought to play an important role in chronic cough and patients are often empirically treated with acid suppression therapy. We sought to investigate the response rate to acid suppression treatment in patients with and without heartburn attending two specialist cough clinics. METHODS: A retrospective review of 558 consecutive patients referred to two specialist cough clinics was performed (UK and USA). Patients who were treated with acid suppression were included and their documented response to treatment was collected. Binary logistic regression was used to ascertain the value of reported heartburn in predicting the response of chronic cough to acid suppression therapy. RESULTS: Of 558 consecutive referrals, 238 patients were excluded due to missing data or cough duration of < 8 weeks. The remaining 320 patients were predominantly female (76%), with mean age 61 yrs (± 13) and 96.8% non-smokers, with chronic cough for 36 (18-117) months. Of 72 patients with heartburn, 20 (28%) noted improvement in their cough with acid suppression, whereas of 248 without heartburn, only 35 (14%) responded. Patients reporting heartburn were 2.7 (95% C.I. 1.3-5.6) times more likely to respond to acid suppression therapy (p = 0.007). CONCLUSION: In specialist cough clinics, few patients report a response of their chronic cough to acid suppression therapy. Nonetheless, heartburn is a useful predictor substantially increasing the likelihood of benefit.
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Reflujo Gastroesofágico , Pirosis , Enfermedad Crónica , Tos/tratamiento farmacológico , Femenino , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/tratamiento farmacológico , Pirosis/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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AIM: Many women do not attend recommended glucose testing following a pregnancy affected by gestational diabetes (GDM). We aimed to synthesize the literature regarding the views and experiences of women with a history of GDM on postpartum glucose testing, focusing on barriers and facilitators to attendance. METHODS: We systematically identified qualitative studies that examine women's experiences following GDM relating to glucose testing (diabetes screening) or experience of interventions to promote uptake of testing. We conducted a thematic synthesis to develop descriptive and then analytical themes, then developed recommendations to increase uptake based on the findings. We evaluated the quality of each study and the confidence that we had in the recommendations using published checklists. RESULTS: We included 16 articles after screening 23 160 citations and 129 full texts. We identified four themes of influences relating to the healthcare system and personal factors that affected both ability and motivation to attend: relationship with health care, logistics of appointments and tests, family-related practicalities and concern about diabetes. We developed 10 recommendations addressing diabetes risk information and education, and changes to healthcare systems to promote increased attendance at screening in this population, most with high or moderate confidence. CONCLUSIONS: We have identified a need to improve women's understanding about Type 2 diabetes and GDM, and to adjust healthcare provision during and after pregnancy to decrease barriers and increase motivation for testing. Encouraging higher uptake by incorporating these recommendations into practice will enable earlier management of diabetes and improve long-term outcomes.
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Diabetes Mellitus Tipo 2/diagnóstico , Tamizaje Masivo , Adulto , Diabetes Gestacional , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Persona de Mediana Edad , Periodo Posparto , Embarazo , Investigación CualitativaRESUMEN
AIM: Complications of gestational diabetes (GDM) can be mitigated if the diagnosis is recognized. However, some at-risk women do not complete antenatal diagnostic oral glucose tolerance testing (OGTT). We aimed to understand reasons contributing to non-completion, particularly to identify modifiable factors. METHODS: Some 1906 women attending a tertiary UK obstetrics centre (2018-2019) were invited for OGTT based on risk-factor assessment. Demographic information, test results and reasons for non-completion were collected from the medical record. Logistic regression was used to analyse factors associated with non-completion. RESULTS: Some 242 women (12.3%) did not complete at least one OGTT, of whom 32.2% (n = 78) never completed testing. In adjusted analysis, any non-completion was associated with younger maternal age [≤ 30 years; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6-3.4; P < 0.001], Black African ethnicity (OR 2.7, 95% CI 1.2-5.5; P = 0.011), lower socio-economic status (OR 0.9, 95% CI 0.8-1.0; P = 0.021) and higher parity (≥ 2; OR 1.8, 95% CI 1.1-2.8; P = 0.013). Non-completion was more likely if testing indications included BMI ≥ 30 kg/m2 (OR 1.7, 95% CI 1.1-2.4; P = 0.009) or family history of diabetes (OR 2.2, 95% CI 1.5-3.3; P < 0.001) and less likely if the indication was an ultrasound finding (OR 0.4, 95% CI 0.2-0.9; P = 0.035). We identified a common overlapping cluster of reasons for non-completion, including inability to tolerate test protocol (21%), social/mental health issues (22%), and difficulty keeping track of multiple antenatal appointments (15%). CONCLUSIONS: There is a need to investigate methods of testing that are easier for high-risk groups to schedule and tolerate, with fuller explanation of test indications and additional support for vulnerable groups.
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Diabetes Gestacional/diagnóstico , Etnicidad/estadística & datos numéricos , Prueba de Tolerancia a la Glucosa/estadística & datos numéricos , Edad Materna , Obesidad Materna/epidemiología , Paridad , Cooperación del Paciente/estadística & datos numéricos , Adulto , Factores de Edad , Población Negra , Femenino , Humanos , Modelos Logísticos , Grupos Minoritarios , Oportunidad Relativa , Embarazo , Atención Prenatal/estadística & datos numéricos , Factores de Riesgo , Clase Social , Ultrasonografía Prenatal , Reino Unido/epidemiologíaRESUMEN
AIMS: After gestational diabetes, many women exhibit behaviours that increase their risk of developing Type 2 diabetes. We aimed to systematically synthesize the literature that focuses on the views of women with a history of gestational diabetes on reducing their risk of developing diabetes postpartum through lifestyle and behaviour changes. METHODS: We identified qualitative studies that examined the views of women with a history of gestational diabetes towards healthy eating and physical activity, Type 2 diabetes risk management or their experience of a diabetes prevention programme, and conducted a thematic synthesis to develop descriptive and then analytical themes. We also evaluated the quality of each study and the confidence that we had in our findings. RESULTS: We included 21 articles after screening 23 160 citations and 129 full texts. We identified six themes of interacting influences on postpartum behaviour: role as mother and priorities; social support; demands of life; personal preferences and experiences; risk perception and information; and finances and resources (plus preferred format of interventions). These factors inhibited many women from addressing their own health, while they motivated others to persevere. We also developed 20 recommendations, most with high or moderate confidence, for effective promotion of healthy lifestyles in this population. CONCLUSIONS: Many factors hinder healthy lifestyles after gestational diabetes, yet how women interpret them can motivate or prevent changes that reduce diabetes risk. As our recommendations emphasize, women's experiences and needs should be considered when designing strategies to promote healthier lifestyles in this population.
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Diabetes Mellitus Tipo 2/prevención & control , Diabetes Gestacional/terapia , Madres/psicología , Percepción , Guías de Práctica Clínica como Asunto , Trastornos Puerperales/prevención & control , Conducta de Reducción del Riesgo , Adulto , Diabetes Mellitus Tipo 2/psicología , Diabetes Gestacional/patología , Diabetes Gestacional/psicología , Progresión de la Enfermedad , Femenino , Conductas Relacionadas con la Salud , Estilo de Vida Saludable/fisiología , Humanos , Estilo de Vida , Madres/estadística & datos numéricos , Embarazo , Trastornos Puerperales/psicologíaRESUMEN
BACKGROUND: Delay to start antiretroviral therapy (ART) and nonadherence compromise the health and wellbeing of people living with HIV (PLWH), raise the cost of care and increase risk of transmission to sexual partners. To date, interventions to improve adherence to ART have had limited success, perhaps because they have failed to systematically elicit and address both perceptual and practical barriers to adherence. The primary aim of this study is to determine the efficacy of the Supporting UPtake and Adherence (SUPA) intervention. METHODS: This study comprises 2 phases. Phase 1 is an observational cohort study, in which PLWH who are ART naïve and recommended to take ART by their clinician complete a questionnaire assessing their beliefs about ART over 12 months. Phase 2 is a randomised controlled trial (RCT) nested within the observational cohort study to investigate the effectiveness of the SUPA intervention on adherence to ART. PLWH at risk of nonadherence (based on their beliefs about ART) will be recruited and randomised 1:1 to the intervention (SUPA intervention + usual care) and control (usual care) arms. The SUPA intervention involves 4 tailored treatment support sessions delivered by a Research Nurse utilising a collaborative Cognitive Behavioural Therapy (CBT) and Motivational Interviewing (MI) approach. Sessions are tailored to individual needs and preferences based on the individual patient's perceptions and practical barriers to ART. An animation series and intervention manual have been developed to communicate a rationale for the personal necessity for ART and illustrate concerns and potential solutions. The primary outcome is adherence to ART measured using Medication Event Monitoring System (MEMS). Three hundred seventy-two patients will be sufficient to detect a 15% difference in adherence with 80% power and an alpha of 0.05. Costs will be compared between intervention and control groups. Costs will be combined with the primary outcome in cost-effectiveness analyses. Quality adjusted life-years (QALYs) will also be estimated over the follow-up period and used in the analyses. DISCUSSION: The findings will enable patients, healthcare providers and policy makers to make informed decisions about the value of the SUPA intervention. TRIAL REGISTRATION: The trial was retrospectively registered 21/02/2014, ISRCTN35514212 .
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Antirretrovirales/uso terapéutico , Terapia Cognitivo-Conductual/métodos , Infecciones por VIH/psicología , Entrevista Motivacional/métodos , Cooperación del Paciente/psicología , Adulto , Terapia Cognitivo-Conductual/economía , Estudios de Cohortes , Análisis Costo-Beneficio , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/economía , Humanos , Masculino , Entrevista Motivacional/economía , Estudios Observacionales como Asunto , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire. METHODS: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries. RESULTS: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals. CONCLUSIONS: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening.
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Neoplasias Colorrectales/epidemiología , Medición de Riesgo/métodos , Anciano , Bancos de Muestras Biológicas , Detección Precoz del Cáncer , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos Teóricos , Sistema de Registros , Encuestas y Cuestionarios , Reino Unido/epidemiologíaRESUMEN
We have made precise measurements of the cyclotron frequency ratios H_{3}^{+}/HD^{+} and H_{3}^{+}/^{3}He^{+} and observe that different H_{3}^{+} ions result in different cyclotron frequency ratios. We interpret these differences as due to the molecular rotational energy of H_{3}^{+} changing its inertial mass. We also confirm that certain high J, K rotational levels of H_{3}^{+} have mean lifetimes exceeding several weeks. From measurements with the lightest H_{3}^{+} ion we obtain lower limits on the atomic masses of deuterium and helium-3 with respect to the proton.
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The NASA Langley airborne second-generation High Spectral Resolution Lidar (HSRL-2) uses a density-tuned field-widened Michelson interferometer to implement the HSRL technique at 355 nm. The Michelson interferometer optically separates the received backscattered light between two channels, one of which is dominated by molecular backscattering, while the other contains most of the light backscattered by particles. This interferometer achieves high and stable contrast ratio, defined as the ratio of particulate backscatter signal received by the two channels. We show that a high and stable contrast ratio is critical for precise and accurate backscatter and extinction retrievals. Here, we present retrieval equations that take into account the incomplete separation of particulate and molecular backscatter in the measurement channels. We also show how the accuracy of the contrast ratio assessment propagates to error in the optical properties. For both backscattering and extinction, larger errors are produced by underestimates of the contrast ratio (compared to overestimates), more extreme aerosol loading, and-most critically-smaller true contrast ratios. We show example results from HSRL-2 aboard the NASA ER-2 aircraft from the 2016 ORACLES field campaign in the southeast Atlantic, off the coast of Africa, during the biomass burning season. We include a case study where smoke aerosol in two adjacent altitude layers showed opposite differences in extinction- and backscatter-related Ångström exponents and a reversal of the lidar ratio spectral dependence, signatures which are shown to be consistent with a relatively modest difference in smoke particle size.
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OBJECTIVES: Many health promotion campaigns and interventions focussing on improving health-related behaviours have been based on targeting response efficacy. This is based on the assumption that response efficacy is an important modifiable determinant of behaviour change. This study aimed to quantify the association between response efficacy and objective and subjective measures of physical activity and diet. STUDY DESIGN: Prospective cohort analysis of data from a randomised controlled trial. METHODS: A total of 953 participants were assessed for response efficacy at baseline and 12 weeks following randomisation to interventions to increase physical activity and improve diet. Subjective measures were collected via a self-report questionnaire that included two questions used to derive the Cambridge Index of physical activity and questions about daily or weekly fruit and vegetable, whole grain, meat and fish intake, based on the dietary guidelines to lower cardiovascular risk. Objective measures were quantified using accelerometers and plasma carotenoids. RESULTS: The mean change in response efficacy for physical activity was +0.5 (standard deviation [SD] 2.0) and for diet was +0.5 (SD 2.1).There were no clinically or statistically significant associations between baseline or change in response efficacy and objective and subjective measures of physical activity or objective measures of diet. There was a small statistically significant association between baseline response efficacy and change in self-reported wholegrain consumption, but this is unlikely to be clinically significant. CONCLUSIONS: Response efficacy is not a fundamental determinant of diet and physical activity and should not be the main focus of interventions targeting these behaviours.
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Dieta/psicología , Ejercicio Físico/psicología , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/prevención & control , Dieta/estadística & datos numéricos , Femenino , Promoción de la Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , AutoinformeRESUMEN
We explored whether supported (SJE) or coordinated joint engagement (CJE) between mothers recruited from the community and their 24-month-old children who were slow-to-talk at 18 months old were associated with child language scores at ages 24, 36, and 48 months (n = 197). We further explored whether SJE or CJE modified the concurrent positive associations between maternal responsive behaviours and language scores. Previous research has shown that SJE, maternal expansions, imitations, and responsive questions were associated with better language scores. Our main finding was that SJE but not CJE was consistently positively associated with 24- and 36-month-old expressive and receptive language scores, but not with 48-month-old language scores. SJE modified how expansions and imitations, but not responsive questions, were associated with language scores; the associations were evident in all but the highest levels of SJE. Further research is necessary to test these findings in other samples before clinical recommendations can be made.
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Trastornos del Desarrollo del Lenguaje , Desarrollo del Lenguaje , Conducta Materna , Relaciones Madre-Hijo , Adulto , Lenguaje Infantil , Preescolar , Femenino , Humanos , Lactante , Lenguaje , Masculino , MadresRESUMEN
BACKGROUND: Children with risk alleles at the 17q21 genetic locus who wheeze during rhinovirus illnesses have a greatly increased likelihood of developing childhood asthma. In mice, overexpression of the 17q21 gene ORMDL3 leads to airway remodelling and hyperresponsiveness. However, the mechanisms by which ORMDL3 predisposes to asthma are unclear. Previous studies have suggested that ORMDL3 induces endoplasmic reticulum (ER) stress and production of the type I interferon (IFN)-regulated chemokine CXCL10. OBJECTIVE: The purpose of this study was to determine the relationship between ORMDL3 and rhinovirus-induced ER stress and type I IFN in human leucocytes. METHODS: ER stress was monitored by measuring HSPA5, CHOP and spliced XBP1 gene expression, and type I IFN by measuring IFNB1 (IFN-ß) and CXCL10 expression in human cell lines and primary leucocytes following treatment with rhinovirus. Requirements for cell contact and specific cell type in ORMDL3 induction were examined by transwell assay and depletion experiments, respectively. Finally, the effects of 17q21 genotype on the expression of ORMDL3, IFNB1 and ER stress genes were assessed. RESULTS: THP-1 monocytes overexpressing ORMDL3 responded to rhinovirus with increased IFNB1 and HSPA5. Rhinovirus-induced ORMDL3 expression in primary leucocytes required cell-cell contact, and induction was suppressed by plasmacytoid dendritic cell depletion. The degree of rhinovirus-induced ORMDL3, HSPA5 and IFNB1 expression varied by leucocyte type and 17q21 genotype, with the highest expression of these genes in the asthma-associated genotype. CONCLUSIONS AND CLINICAL RELEVANCE: Multiple lines of evidence support an association between higher ORMDL3 and increased rhinovirus-induced HSPA5 and type I IFN gene expression. These associations with ORMDL3 are cell type specific, with the most significant 17q21 genotype effects on ORMDL3 expression and HSPA5 induction evident in B cells. Together, these findings have implications for how the interaction of increased ORMDL3 and rhinovirus may predispose to asthma.
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Estrés del Retículo Endoplásmico/genética , Interferón Tipo I/metabolismo , Leucocitos/metabolismo , Proteínas de la Membrana/genética , Infecciones por Picornaviridae/genética , Infecciones por Picornaviridae/metabolismo , Rhinovirus/fisiología , Adulto , Asma/etiología , Asma/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Línea Celular , Cromosomas Humanos Par 17 , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Chaperón BiP del Retículo Endoplásmico , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Genotipo , Proteínas de Choque Térmico/genética , Humanos , Interferón Tipo I/genética , Persona de Mediana Edad , Infecciones por Picornaviridae/virologíaRESUMEN
To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.
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Moléculas de Adhesión Celular/genética , Función Ejecutiva/fisiología , Anciano , Anciano de 80 o más Años , Moléculas de Adhesión Celular/fisiología , Cognición/fisiología , Estudios de Cohortes , Femenino , Estudios de Asociación Genética , Variación Genética/genética , Estudio de Asociación del Genoma Completo , Genómica , Humanos , Intrones , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Ácido gamma-AminobutíricoRESUMEN
BACKGROUND: Most people with psoriasis have limited disease that could be treated with topicals, but topical efficacy is limited by low short-term adherence. Psoriasis is a chronic disease, and long-term adherence is an even bigger problem. OBJECTIVES: To determine how well medication is used in the long-term topical treatment of psoriasis and to assess the potential of an internet-based reporting intervention to improve treatment adherence and outcomes. METHODS: An investigator-blinded, prospective study evaluated topical fluocinonide adherence in 40 patients with mild-to-moderate psoriasis over 12 months. Subjects were randomized in a 1 : 1 ratio to standard-of-care or internet-based reporting group. Adherence was objectively monitored with Medication Event Monitoring System® caps. RESULTS: Fifty per cent of subjects discontinued the treatment. Greater adherence was seen in the intervention group compared with the standard-of-care group (50% vs. 35%, P = 0·08). Psoriasis Area and Severity Index improved more in the intervention group at month 1 (1·61 vs. -0·12, P = 0·003), month 3 (2·50 vs. 0·79, P = 0·025) and month 12 (3·32 vs. 0·34, P = 0·038) than in the standard-of-care group. CONCLUSIONS: This study likely underestimates the challenge of long-term adherence, as adherence tends to be better in research studies than in clinical practice. This study also did not fully account for primary nonadherence. Adherence to topical treatment is low in the short term and decreased further in the long term, a considerable challenge for dermatologists to address. A reporting intervention may be one of the ways we can improve our patients' treatment outcomes.