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This was a longitudinal study utilising the Irish Longitudinal Study on Ageing (n 3849 aged ≥ 50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). A score ≥ 9 on the Center for Epidemiological Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. B12 status profiles (pmol/l) were defined as < 185, deficient low; 185 to < 258, low normal; > 258-601, normal and > 601 high. Folate status profiles (nmol/l) were defined as ≤ 10·0, deficient low; > 10-23·0, low normal; > 23·0-45·0, normal; >45·0, high. Logistic regression models were used to analyse the longitudinal associations. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms v. non-depressed (folate: 21·4 v. 25·1 nmol/l; P = 0·0003; B12:315·7 v. 335·9 pmol/l; P = 0·0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression 4 years later (OR 1·51, 95 % CI 1·01, 2·27, P = 0·043). This finding remained robust after controlling for relevant covariates. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51 % increased likelihood of developing depressive symptoms over 4 years. The findings highlight the need to further explore the low-cost benefits of optimising vitamin B12 status for depression in older adults.
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Depresión , Ácido Fólico , Humanos , Anciano , Estudios Longitudinales , Depresión/epidemiología , Vida Independiente , VitaminasRESUMEN
The lung epithelium forms the first barrier against respiratory pathogens and noxious chemicals; however, little is known about how more than 90% of this barrier, made of AT1 (alveolar type 1) cells, responds to injury. Using the Sendai virus to model natural infection in mice, we find evidence that AT1 cells have an intermediary role by persisting in areas depleted of AT2 cells, upregulating IFN responsive genes, and receding from invading airway cells. Sendai virus infection mobilizes airway cells to form alveolar SOX2+ (Sry-box 2+) clusters without differentiating into AT1 or AT2 cells. Large AT2 cell-depleted areas remain covered by AT1 cells, which we name "AT2-less regions", and are replaced by SOX2+ clusters spreading both basally and luminally. AT2 cell proliferation and differentiation are largely confined to topologically distal regions and form de novo alveolar surface, with limited contribution to in situ repairs of AT2-less regions. Time-course single-cell RNA sequencing profiling and RNAscope validation suggest enhanced immune responses and altered growth signals in AT1 cells. Our comprehensive spatiotemporal and genomewide study highlights the hitherto unappreciated role of AT1 cells in lung injury-repair.
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Células Epiteliales Alveolares , Infecciones por Respirovirus , Células Epiteliales Alveolares/metabolismo , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Pulmón , RatonesRESUMEN
BACKGROUND: Chronic diseases are the leading cause of death worldwide. Many of these diseases have modifiable risk factors, including physical activity and sleep, and may be preventable. This study investigated independent associations of physical activity and sleep with eight common chronic illnesses. METHODS: Data were from waves 1, 3 and 5 of The Irish Longitudinal Study on Ageing (n = 5,680). Inverse probability weighted general estimating equations were used to examine longitudinal lifetime prevalence and cumulative incidence of self-reported conditions. RESULTS: Sleep problems were significantly associated with increased odds of incident and prevalent arthritis and angina. Additionally sleep problems were associated with higher odds of lifetime prevalence of hypertension and diabetes. Physical activity was negatively associated incident osteoporosis and respiratory diseases and negatively associated with lifetime prevalence of hypertension, high cholesterol and diabetes. CONCLUSIONS: Worse sleep quality and lower physical activity were associated with higher odds of chronic diseases. Interventions to improve sleep and physical activity may improve health outcomes.
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Hipertensión , Trastornos del Sueño-Vigilia , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Ejercicio Físico , Humanos , Incidencia , Estudios Longitudinales , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Sueño , Trastornos del Sueño-Vigilia/epidemiologíaRESUMEN
BACKGROUND: Orthostatic hypotension (OH) can be assessed with non-invasive continuous beat-to-beat haemodynamic monitoring during active stand (AS) testing; this yields large volumes of data outside the scope of the traditional OH definition. We explored clinical associations of different AS patterns in participants from Wave 1 of the Irish Longitudinal Study on Ageing. METHODS: AS patterns were generated based on three sequential binary systolic blood pressure features: drop ≥40 mmHg within 10 sec post-stand ("immediate deficit"), failure to return to within 20 mmHg of supine level at 40 sec after standing ("stabilisation deficit") and drop ≥20 mmHg between >40 and 120 sec post-stand ("late deficit"). Eight AS groups resulted from combining the presence/absence of these three features. The groups were cross-sectionally characterised, and their ability to independently predict orthostatic intolerance (OI) during AS, and falls or syncope in the past year, was evaluated using multivariate logistic regression models. RESULTS: A total of 4,899 participants were included (mean age 61), of which 3,312 (68%) had no deficits. Older age was associated with stabilisation deficit and late deficits were seen in groups with higher proportions of beta blockers and psychotropic medications. Regression models identified independent associations between OI and three immediate-deficit groups; associations seemed stronger as more deficits were present. There was a significant association between falls history and the three-deficit group (odds ratio 1.54, 95% confidence interval: 1.15-2.07, P = 0.004). CONCLUSIONS: More deficits seemed associated with the higher risk of OI and falls history. Observations are not causal but the recognition of these patterns may help clinicians focus on careful prescribing.
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Hipotensión Ortostática , Anciano , Envejecimiento , Presión Sanguínea , Análisis por Conglomerados , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/epidemiología , Estudios LongitudinalesRESUMEN
BACKGROUND: Identification of those who are most at risk of developing specific patterns of disease across different populations is required for directing public health policy. Here, we contrast prevalence and patterns of cross-national disease incidence, co-occurrence and related risk factors across population samples from the U.S., Canada, England and Ireland. METHODS: Participants (n = 62,111) were drawn from the US Health and Retirement Study (n = 10,858); the Canadian Longitudinal Study on Ageing (n = 36,647); the English Longitudinal Study of Ageing (n = 7938) and The Irish Longitudinal Study on Ageing (n = 6668). Self-reported lifetime prevalence of 10 medical conditions, predominant clusters of multimorbidity and their specific risk factors were compared across countries using latent class analysis. RESULTS: The U.S. had significantly higher prevalence of multimorbid disease patterns and nearly all diseases when compared to the three other countries, even after adjusting for age, sex, BMI, income, employment status, education, alcohol consumption and smoking history. For the U.S. the most at-risk group were younger on average compared to Canada, England and Ireland. Socioeconomic gradients for specific disease combinations were more pronounced for the U.S., Canada and England than they were for Ireland. The rates of obesity trends over the last 50 years align with the prevalence of eight of the 10 diseases examined. While patterns of disease clusters and the risk factors related to each of the disease clusters were similar, the probabilities of the diseases within each cluster differed across countries. CONCLUSIONS: This information can be used to better understand the complex nature of multimorbidity and identify appropriate prevention and management strategies for treating multimorbidity across countries.
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Punto Alto de Contagio de Enfermedades , Canadá/epidemiología , Humanos , Irlanda , Estudios Longitudinales , Prevalencia , Estados UnidosRESUMEN
METHODS: Data from a nationally representative sample of 4,069 U.S. veterans in 2019-2020 were used to examine the prevalence of full and subthreshold PTSD in veterans with a history of homelessness; identify characteristics associated with PTSD; examine the proportion of veterans who reported homelessness as an index trauma event and screened positive for PTSD. RESULTS: Among veterans with a history of homelessness, lifetime prevalence of full and subthreshold PTSD was 33.0% and 32.0%; and past-month prevalence of full and subthreshold PTSD was 5.6% and 12.7%. These prevalence estimates were more than five times higher than nonhomeless veterans. Among veterans with a history of homelessness, 14.1% reported that homelessness was their "worst" traumatic event which was associated with a fivefold greater odds of current PTSD and nearly threefold greater odds of subthreshold PTSD even after adjustment for other trauma exposures. CONCLUSIONS: Veterans who have been homeless have extensive trauma histories and both events that occur during homelessness and the experience of homelessness itself may be traumatic and lead to PTSD, substantiating efforts to provide trauma-informed care for this population.
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Personas con Mala Vivienda , Trastornos por Estrés Postraumático , Veteranos , Humanos , Prevalencia , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
In this study, we present a newly developed observational system, Optimizing Learning Opportunities for Students (OLOS). OLOS is designed to elucidate the learning opportunities afforded to individual children within early childhood classrooms and as they transition to formal schooling (kindergarten through third grade). OLOS records the time spent in different types of learning opportunities (e.g., play, literacy, math) and the frequency of specific discourse moves children and teachers use (child talk and teacher talk). Importantly, it is being designed to be used validly and reliably by practitioners. Using OLOS, we explored individual children's experiences (n = 68 children in 12 classrooms) in four different types of early childhood programs; state-funded, state-funded PK serving children with disabilities, Head Start, and a tuition-based (non-profit) preschool. Results of our feasibility study revealed that we could feasibly and reliably use OLOS in these very different kinds of pre-kindergarten programs with some changes. OLOS provided data that aligned with our hypotheses and that our practitioner partners found useful. In analysing the observations, we found that individual children's learning opportunities varied significantly both within and between classrooms. In general, we observed that most of the PK day (or half day) was spent in language and literacy activities and non-instructional activities (e.g., transitions). Very little time in math and science was observed yet children were generally more likely to actively participate (i.e., more child talk) during academic learning opportunities (literacy, math, and science). The frequency of teacher talk also varied widely between classrooms and across programs. Plus, the more teacher talk we observed, the more likely we were to observe child talk. Our long-term aim is that OLOS can inform policy and provide information that supports practitioners in meeting the learning and social-behavioral needs of the children they serve.
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Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth.
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Células Epiteliales Alveolares/citología , Plasticidad de la Célula/fisiología , Reprogramación Celular/fisiología , Enfermedades Pulmonares/patología , Alveolos Pulmonares/embriología , Animales , Diferenciación Celular , Células Cultivadas , Células Epiteliales/citología , Imagenología Tridimensional , Hibridación Fluorescente in Situ , Ratones , Ratones Transgénicos , Neovascularización Fisiológica/fisiología , Alveolos Pulmonares/citología , Factores de Transcripción SOXB1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVES: The International League of Associations for Rheumatology classification criteria define systemic juvenile idiopathic arthritis (SJIA) by the presence of fever, rash and chronic arthritis. Recent initiatives to revise current criteria recognise that a lack of arthritis complicates making the diagnosis early, while later a subgroup of patients develops aggressive joint disease. The proposed biphasic model of SJIA also implies a 'window of opportunity' to abrogate the development of chronic arthritis. We aimed to identify novel SJIA biomarkers during different disease phases. METHODS: Children with active SJIA were subgrouped clinically as systemic autoinflammatory disease with fever (SJIA syst ) or polyarticular disease (SJIA poly ). A discovery cohort of n=10 patients per SJIA group, plus n=10 with infection, was subjected to unbiased label-free liquid chromatography mass spectrometry (LC-MS/MS) and immunoassay screens. In a separate verification cohort (SJIA syst , n=45; SJIA poly , n=29; infection, n=32), candidate biomarkers were measured by multiple reaction monitoring MS (MRM-MS) and targeted immunoassays. RESULTS: Signatures differentiating the two phenotypes of SJIA could be identified. LC-MS/MS in the discovery cohort differentiated SJIA syst from SJIA poly well, but less effectively from infection. Targeted MRM verified the discovery data and, combined with targeted immunoassays, correctly identified 91% (SJIA syst vs SJIA poly ) and 77% (SJIA syst vs infection) of all cases. CONCLUSIONS: Molecular signatures differentiating two phenotypes of SJIA were identified suggesting shifts in underlying immunological processes in this biphasic disease. Biomarker signatures separating SJIA in its initial autoinflammatory phase from the main differential diagnosis (ie, infection) could aid early-stage diagnostic decisions, while markers of a phenotype switch could inform treat-to-target strategies.
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Artritis Juvenil/clasificación , Artritis Juvenil/patología , Fenotipo , Proteómica , Adolescente , Análisis de Varianza , Área Bajo la Curva , Artritis Juvenil/sangre , Biomarcadores/análisis , Niño , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Masculino , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Espectrometría de Masas en Tándem/métodosRESUMEN
Objectives. To test the efficacy of Me & You, a multilevel technology-enhanced adolescent dating violence (DV) intervention, in reducing DV perpetration and victimization among ethnic-minority early adolescent youths. We assessed secondary impact for specific DV types and psychosocial outcomes.Methods. We conducted a group-randomized controlled trial of 10 middle schools from a large urban school district in Southeast Texas in 2014 to 2015. We used multilevel regression modeling; the final analytic sample comprised 709 sixth-grade students followed for 1 year.Results. Among the total sample, odds of DV perpetration were lower among intervention students than among control students (adjusted odds ratio = 0.46; 95% confidence interval = 0.28, 0.74). Odds of DV victimization were not significantly different. There were significant effects on some specific DV types.Conclusions. Me & You is effective in reducing DV perpetration and decreasing some forms of DV victimization in early middle-school ethnic-minority students.
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Víctimas de Crimen/estadística & datos numéricos , Etnicidad , Promoción de la Salud/organización & administración , Violencia de Pareja/prevención & control , Servicios de Salud Escolar/organización & administración , Adolescente , Conducta del Adolescente/psicología , Niño , Víctimas de Crimen/psicología , Humanos , Violencia de Pareja/psicología , Evaluación de Programas y Proyectos de Salud , Texas , Población UrbanaRESUMEN
INTRODUCTION: Diffusion of sexual health evidence-based programs (EBPs) in schools is a complex and challenging process. iCHAMPSS ( CHoosing And Maintaining effective Programs for Sex education in Schools) is an innovative theory- and Web-based decision support system that may help facilitate this process. The purpose of this study was to pilot-test iCHAMPSS for usability and short-term psychosocial impact. METHOD: School district stakeholders from across Texas were recruited ( N = 16) and given access to iCHAMPSS for 3 weeks in fall 2014. Pre- and posttests were administered to measure usability parameters and short-term psychosocial outcomes. Data were analyzed using descriptive statistics and the Wilcoxon signed-rank test. RESULTS: Most participants reported that iCHAMPSS was easy to use, credible, helpful, and of sufficient motivational appeal. iCHAMPSS significantly increased participants' self-efficacy to obtain approval from their board of trustees to implement a sexual health EBP. Positive, though nonsignificant, trends included increased knowledge to locate EBPs, skills to prioritize sexual health education at the district level, and ability to choose an EBP that best meets district needs. CONCLUSIONS: iCHAMPSS is an innovative decision support system that could accelerate uptake of EBPs by facilitating diffusion and advance the field of dissemination and implementation science for the promotion of sexual health EBPs.
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Conocimientos, Actitudes y Práctica en Salud , Servicios de Salud Escolar/organización & administración , Educación Sexual/organización & administración , Práctica Clínica Basada en la Evidencia , Femenino , Humanos , Masculino , Proyectos Piloto , Salud Reproductiva , Autoeficacia , TexasRESUMEN
Much is known about the prevalence and correlates of dating violence, especially the perpetration of physical dating violence, among older adolescents. However, relatively little is known about the prevalence and correlates of the perpetration of cyber dating abuse, particularly among early adolescents. In this study, using a predominantly ethnic-minority sample of sixth graders who reported ever having had a boyfriend/girlfriend (n = 424, 44.2 % female), almost 15 % reported perpetrating cyber dating abuse at least once during their lifetime. Furthermore, using a cross-sectional design, across multiple levels of the socio-ecological model, the individual-level factors of (a) norms for violence for boys against girls, (b) having a current boyfriend/girlfriend, and (c) participation in bullying perpetration were correlates of the perpetration of cyber dating abuse. Collectively, the findings suggest that dating violence interventions targeting these particular correlates in early adolescents are warranted. Future studies are needed to establish causation and to further investigate the relative importance of correlates of the perpetration of cyber dating abuse among early adolescents that have been reported among older adolescents.
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Conducta del Adolescente/psicología , Violencia de Pareja/estadística & datos numéricos , Red Social , Adolescente , Acoso Escolar , Estudios Transversales , Femenino , Humanos , Relaciones Interpersonales , Masculino , PrevalenciaRESUMEN
BACKGROUND: Academic-military research collaborations are desirable for many reasons; however, little guidance in the literature exists to help researchers understand collaboration requirements. PURPOSE: To describe the process for establishing academic-military research collaborations. METHOD: Specific collaboration requirements researchers must be aware of are outlined, two case studies are provided, and opportunities for and challenges with collaborations are discussed. DISCUSSION: Academic-military collaborations made it possible to conduct studies of stigma and barriers with mental health care among military nursing personnel and the utilization of secure messaging for health concerns with service members and healthcare providers. Planning these efforts began in the earliest stages of developing research proposals, and additional time was required to complete regulatory requirements prior to study implementation. Understanding military-specific considerations and establishing clear expectations and responsibilities were essential. CONCLUSIONS: Despite the challenges involved, academic-military collaborations improve the quality of the research by enhancing access to funding, expertise, and resources.
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Investigación Biomédica , Educación en Enfermería , Enfermería Militar , Personal Militar , Conducta Cooperativa , Humanos , Estados UnidosRESUMEN
BACKGROUND: Identification of gene expression profiles that differentiate experimental groups is critical for discovery and analysis of key molecular pathways and also for selection of robust diagnostic or prognostic biomarkers. While integration of differential expression statistics has been used to refine gene set enrichment analyses, such approaches are typically limited to single gene lists resulting from simple two-group comparisons or time-series analyses. In contrast, functional class scoring and machine learning approaches provide powerful alternative methods to leverage molecular measurements for pathway analyses, and to compare continuous and multi-level categorical factors. RESULTS: We introduce GOexpress, a software package for scoring and summarising the capacity of gene ontology features to simultaneously classify samples from multiple experimental groups. GOexpress integrates normalised gene expression data (e.g., from microarray and RNA-seq experiments) and phenotypic information of individual samples with gene ontology annotations to derive a ranking of genes and gene ontology terms using a supervised learning approach. The default random forest algorithm allows interactions between all experimental factors, and competitive scoring of expressed genes to evaluate their relative importance in classifying predefined groups of samples. CONCLUSIONS: GOexpress enables rapid identification and visualisation of ontology-related gene panels that robustly classify groups of samples and supports both categorical (e.g., infection status, treatment) and continuous (e.g., time-series, drug concentrations) experimental factors. The use of standard Bioconductor extension packages and publicly available gene ontology annotations facilitates straightforward integration of GOexpress within existing computational biology pipelines.
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Biología Computacional/métodos , Ontología de Genes , Programas Informáticos , Aprendizaje Automático Supervisado , Transcriptoma , ARN MensajeroRESUMEN
OBJECTIVE: Biological therapies, which include antitumour necrosis factor-α and T-cell inhibitors, are potentially effective treatments for psoriatic arthritis (PsA) but are costly and may induce a number of side effects. Response to treatment in PsA is variable and difficult to predict. Here, we sought to identify a panel of protein biomarkers that could be used to predict which patients diagnosed with PsA will respond to biologic treatment. METHODS: An integrated discovery to targeted proteomics approach was used to investigate the protein profiles of good and non-responders to biological treatments in patients with PsA. Reverse-phase liquid chromatography coupled to tandem mass spectrometry was used to generate protein profiles of synovial tissue obtained at baseline from 10 patients with PsA. Targeted proteomics using multiple reaction monitoring (MRM) was used to confirm and prevalidate a potential protein biomarker panel in 18 and 7 PsA patient samples, respectively. RESULTS: A panel of 107 proteins was selected, and targeted mass spectrometry MRM assays were successfully developed for 57 of the proteins. The 57 proteins include S100-A8, S100-A10, Ig kappa chain C fibrinogen-α and γ, haptoglobin, annexin A1 and A2, collagen alpha-2, vitronectin, and alpha-1 acid glycoprotein. The proteins were measured simultaneously and confirmed to be predictive of response to treatment with an area under the curve of 0.76. In a blinded study using a separate cohort of patients, the panel was able to predict response to treatment. CONCLUSIONS: The approach reported here and the initial data provide evidence that a multiplexed protein assay of a panel of biomarkers that predict response to treatment could be developed. TRIAL REGISTRATION NUMBER: ISRCTN23328456.
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Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Biomarcadores/metabolismo , Artritis Psoriásica/diagnóstico , Método Doble Ciego , Femenino , Humanos , Masculino , Pronóstico , Proteínas/metabolismo , Proteómica/métodos , Membrana Sinovial/metabolismo , Resultado del TratamientoRESUMEN
Although sexual behaviors have been extensively studied among youth in general, they have been relatively understudied among military-dependent youth (MDY). Furthermore, the impact of unique military stressors, such as parental deployment and multiple relocations, on the sexual behaviors of MDY has not been assessed. In this pilot study, we estimated the prevalence of sexual behaviors among MDY, and examined the association between these behaviors and parental deployment and multiple relocations. Between June and September 2011, we recruited youth (N = 208; aged 15-19 years) who attended a military treatment facility in the southern United States, to complete a short, paper-based survey. We computed prevalence estimates and conducted Chi-square analyses, as well as logistic regression analyses, while adjusting for age, gender, and race/ethnicity. More than half (53.7 %) of the youth reported being sexually experienced, and many of these youth reported engaging in risky sexual behaviors. Parental deployment and multiple relocations were significantly associated only with having had sex in the past 3 months. Although with most sexual behaviors there was no significant association between parental deployment and multiple relocations, many MDY are sexually experienced and engage in risky sexual behaviors. MDY should thus be exposed to evidence-based strategies for sexually transmitted infection and pregnancy prevention, as well as provided with teen-friendly health care services and comprehensive sexual/reproductive health counseling.
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Personal Militar , Padres , Sexo Inseguro/estadística & datos numéricos , Adolescente , Factores de Edad , Femenino , Humanos , Masculino , Personal Militar/estadística & datos numéricos , Relaciones Padres-Hijo , Factores Sexuales , Conducta Sexual/psicología , Conducta Sexual/estadística & datos numéricos , Encuestas y Cuestionarios , Sexo Inseguro/psicología , Adulto JovenRESUMEN
Proteomic biomarker discovery has led to the identification of numerous potential candidates for disease diagnosis, prognosis, and prediction of response to therapy. However, very few of these identified candidate biomarkers reach clinical validation and go on to be routinely used in clinical practice. One particular issue with biomarker discovery is the identification of significantly changing proteins in the initial discovery experiment that do not validate when subsequently tested on separate patient sample cohorts. Here, we seek to highlight some of the statistical challenges surrounding the analysis of LC-MS proteomic data for biomarker candidate discovery. We show that common statistical algorithms run on data with low sample sizes can overfit and yield misleading misclassification rates and AUC values. A common solution to this problem is to prefilter variables (via, e.g. ANOVA and or use of correction methods such as Bonferonni or false discovery rate) to give a smaller dataset and reduce the size of the apparent statistical challenge. However, we show that this exacerbates the problem yielding even higher performance metrics while reducing the predictive accuracy of the biomarker panel. To illustrate some of these limitations, we have run simulation analyses with known biomarkers. For our chosen algorithm (random forests), we show that the above problems are substantially reduced if a sufficient number of samples are analyzed and the data are not prefiltered. Our view is that LC-MS proteomic biomarker discovery data should be analyzed without prefiltering and that increasing the sample size in biomarker discovery experiments should be a very high priority.
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Espectrometría de Masas/métodos , Proteómica/métodos , Algoritmos , Inteligencia Artificial , Biomarcadores/análisis , Cromatografía Liquida/métodos , Simulación por Computador , Árboles de Decisión , Humanos , Modelos Estadísticos , Tamaño de la Muestra , Estudios de Validación como AsuntoRESUMEN
Background: An integrated haemodynamic response during standing may serve as an integrative marker of neuro-cardiovascular function. Individual components of both heart rate (HR) and blood pressure (BP) responses to active stand (AS) have been linked with cardiovascular disease (CVD) and mortality. We assessed longitudinal associations between entire HR/BP response curves during AS, incident CVD and mortality over 12 years. Methods: Beat-to-beat measurements of dynamic HR/BP responses to AS were conducted in 4,336 individuals (61.5±8.2 years; 53.7% female). Functional Principal Components Analysis was applied to HR/BP response curves and their association with CVD and mortality assessed. We hypothesised that integrating BP/HR information from the entire haemodynamic response curve may uncover novel associations with both CVD and mortality. Results: Higher systolic BP (SBP) before AS and blunted recovery of SBP during AS was associated with all-cause mortality over 12-years (Hazard Ratio [HR]: 1.14; 1.04, 1.26; p=0.007). Higher baseline/peak HR and lower HR from 30 seconds post stand onwards were associated with lower mortality due to circulatory causes (HR: 0.78; 0.64, 0.95; p = 0.013). Higher HR throughout AS was associated with mortality from other causes (HR: 1.48; 1.22, 1.80; p<0.001). Findings persisted on robust covariate adjustment. Conclusions: We observed distinct relationships between HR/BP responses to AS and 12-year incident CVD and mortality. Integrating the entire haemodynamic response may reveal more nuanced relationships between HR/BP responses to AS, CVD and mortality - serving as an integrative marker of neuro-cardiovascular health in midlife and beyond.
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BACKGROUND: Although type 2 diabetes mellitus (T2DM) is an established risk factor for cognitive impairment, the underlying mechanisms remain poorly explored. One potential mechanism may be through effects of T2DM on cerebral perfusion. The current study hypothesized that T2DM is associated with altered peripheral and central hemodynamic responses to orthostasis, which may in turn be associated with cognitive impairment in T2DM. METHODS: A novel use of function-on-scalar regression, which allows the entire hemodynamic response curve to be modeled, was employed to assess the association between T2DM and hemodynamic responses to orthostasis. Logistic regression was used to assess the relationship between tissue saturation index (TSI), T2DM, and cognitive impairment. All analyses used cross-sectional data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA). RESULTS: Of 2 984 older adults (aged 64.3â ±â 8.0; 55% female), 189 (6.3%) had T2DM. T2DM was associated with many features that are indicative of autonomic dysfunction including a blunted peak heart rate and lower diastolic blood pressure. T2DM was associated with reduced TSI and also with greater odds of impaired performance on the Montreal Cognitive Assessment (odds ratio [OR]: 1.62; confidence interval [CI: 1.07, 2.56]; pâ =â .019). Greater TSI was associated with lower odds of impaired performance (OR: 0.90, CI [0.81-0.99]; pâ =â .047). CONCLUSIONS: T2DM was associated with impaired peripheral and cerebral hemodynamic responses to active stand. Both T2DM and reduced cerebral perfusion were associated with impaired cognitive performance. Altered cerebral perfusion may represent an important mechanism linking T2DM and adverse brain health outcomes in older adults.
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Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Femenino , Anciano , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Estudios Longitudinales , Mareo , Estudios Transversales , Disfunción Cognitiva/etiología , HemodinámicaRESUMEN
Background: Impaired recovery of blood pressure (BP) in response to standing up is a prevalent condition in older individuals. We evaluated the relationship between the early recovery of hemodynamic responses to standing and brain health in adults over 50. Methods: Participants from The Irish Longitudinal Study on Ageing (TILDA) (n=411; age 67.6 ± 7.3 years; 53.4 % women) performed an active stand challenge while blood pressure and heart rate were continuously monitored. The recovery of these parameters was determined as the slope of the BP and HR response, following the initial drop/rise after standing. We have previously reported a novel and validated measure of brain ageing using MRI data, which measures the difference between biological brain age and chronological age, providing a brain-predicted age difference (brainPAD) score. Results: Slower recovery of systolic and diastolic BP was found to be significantly associated with higher brainPAD scores (i.e., biologically older brains), where a one-year increase in brainPAD was associated with a decrease of 0.02 mmHg/s and 0.01 mmHg/s in systolic and diastolic BP recovery, respectively, after standing. Heart rate (HR) recovery was not significantly associated with brainPAD score. Conclusion: These results demonstrate that slower systolic and diastolic BP recovery in the early phase after standing is associated with accelerated brain aging in older individuals. This suggests that the BP response to standing, measured using beat-to-beat monitoring, has the potential to be used as a marker of accelerated brain aging, relying on a simple procedure and devices that are easily accessible.