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Two-dimensional (2D) hybrid organic-inorganic perovskites (HOIPs) with enhanced stability, high tunability, and strong spin-orbit coupling have shown great potential in vast applications. Here, we extend the already rich functionality of 2D HOIPs to a new territory, realizing topological superconductivity and Majorana modes for fault-tolerant quantum computation. Especially, we predict that room-temperature ferroelectric BA2PbCl4 (BA for benzylammonium) exhibits topological nodal-point superconductivity (NSC) and gapless Majorana modes on selected edges and ferroelectric domain walls when proximity-coupled to an s-wave superconductor and an in-plane Zeeman field, attractive for experimental verification and application. Since NSC is protected by spatial symmetry of 2D HOIPs, we envision more exotic topological superconducting states to be found in this class of materials due to their diverse noncentrosymmetric space groups, which may open a new avenue in the fields of HOIPs and topological superconductivity.
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BACKGROUND: Social isolation and social connectedness are health determinants and aspects of social well-being with strong associations with psychological distress. This study evaluated relationships among social isolation, social connectedness, and psychological distress (i.e., depression, anxiety) over 1 year in young adult (YA) cancer survivors 18-39 years old. METHODS: Participants were YAs in a large cohort study that completed questionnaires every 2 months for 1 year. Social isolation, aspects of social connectedness (i.e., companionship, emotional support, instrumental support, and informational support), depression, and anxiety were assessed with Patient-Reported Outcomes Measurement Information System short form measures. Mixed-effect models were used to evaluate changes over time. Confirmatory factor analysis and multilevel structural equation modeling were used to define social connectedness as a latent construct and determine whether relationships between social isolation and psychological distress were mediated by social connectedness. RESULTS: Participants (N = 304) were mean (M) = 33.5 years old (SD = 4.7) and M = 4.5 years (SD = 3.5) post-initial cancer diagnosis. Most participants were female (67.4%) and non-Hispanic White (68.4%). Average scores for social well-being and psychological distress were within normative ranges and did not change (p values >.05). However, large proportions of participants reported at least mild social isolation (27%-30%), depressive symptoms (36%-37%), and symptoms of anxiety (49%-51%) at each time point. Across participants, more social isolation was related to less social connectedness (p values <.001), more depressive symptoms (p < .001), and more symptoms of anxiety (p < .001). Social connectedness mediated the relationship between social isolation and depression (p = .004), but not anxiety (p > .05). CONCLUSIONS: Social isolation and connectedness could be intervention targets for reducing depression among YA cancer survivors.
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OBJECTIVE: There is a dearth of literature describing young adult (YA) cancer survivors' experiences with cancer-related cognitive impairment (CRCI). We aimed to elucidate CRCI among YA cancer survivors and identify potentially modifiable risk factors. METHODS: We conducted individual qualitative interviews with YA cancer survivors aged 18-30 years at study enrollment and used applied thematic analysis to identify themes across three topics (i.e., affected cognitive abilities, risk and protective factors influencing the impact of CRCI, and strategies for coping with CRCI). RESULTS: YA cancer survivors (N = 20) were, on average, 23 years old at diagnosis and 26 years old when interviewed. Diverse cancer types and treatments were represented; most participants (85%) had completed cancer treatment. Participants described experiences across three qualitative topics: (1) affected cognitive abilities (i.e., concentration and attention, prospective memory, and long-term memory), (2) Risk factors (i.e., fatigue, sleep problems, mood, stress/distractions, and social isolation) and protective factors (i.e., social support), and (3) coping strategies, including practical strategies that helped build self-efficacy (e.g., writing things down, reducing distractions), beneficial emotion-focused coping strategies (e.g., focus on health, faith/religion), strategies with mixed effects (i.e., apps/games, medications/supplements, and yoga), and "powering through" strategies that exacerbated stress. CONCLUSIONS: YA cancer survivors experience enduring cognitive difficulties after treatment. Specific concerns highlight the importance of attention and executive functioning impairments, long-term memory recall, and sensitivity to distractions. Future work is needed to improve assessment and treatment of CRCI among YA cancer survivors.
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Sobreviventes de Câncer , Disfunção Cognitiva , Neoplasias , Humanos , Adulto Jovem , Adulto , Sobreviventes de Câncer/psicologia , Cognição , Disfunção Cognitiva/etiologia , Neoplasias/psicologia , EncéfaloRESUMO
BACKGROUND: Risk factors for cancer-related fatigue are understudied in colorectal cancer. PURPOSE: This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. METHODS: Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. RESULTS: Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III-IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (ß = 0.26, p = .016). When stratified by cancer stage (I-II vs. III-IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, ß = 0.43, p = .035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. CONCLUSIONS: Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. TRIAL REGISTRATION: The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014.
Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced (Stages III and IV) colorectal cancer the first year after diagnosis.
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Neoplasias Colorretais , Transtornos do Sono-Vigília , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Colorretais/complicações , Estudos Transversais , Exercício Físico , Fadiga/complicações , Qualidade de Vida , Sono , Transtornos do Sono-Vigília/complicaçõesRESUMO
Bioinformatics analysis was performed to reveal the underlying pathogenesis of type 2 diabetes (T2DM) dry eye(DE) and to predict the core targets and potential pathways for electroacupuncture (EA) treatment of T2DM DE, in which key targets such as Toll-likereceptor4 (TLR4), NF-κB and Tumor necrosis factor-α (TNF-α) may be involved. Next, streptozotocin and a high-fat diet were used to generate T2DM-DE rats. Randomly picked EA, fluorometholone, model, and sham EA groups were created from successfully modelled T2DM DE rats. Six more rats were chosen as the blank group from among the normal rats. The results of DE index showed that EA improved the ocular surface symptoms.HE staining showed that EA attenuated the pathological changes in the cornea, conjunctiva and lacrimal gland of T2DM DE rats. EA decreased the expression of TLR4, MyD88, P-NF-κB P65, and TNF-α in the cornea, conjunctiva, and lacrimal gland, in accordance with immunofluorescence and Western blot data. Thus, EA reduced ocular surface symptoms and improved pathological changes of cornea, conjunctiva, and lacrimal gland induced by T2DM DE inT2DM DE rats, and the mechanism may be related to the inhibition of overactivation of the TLR4/NF-κB signaling pathway by EA and thus attenuating ocular surface inflammation.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Síndromes do Olho Seco , Eletroacupuntura , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Animais , Receptor 4 Toll-Like/metabolismo , Eletroacupuntura/métodos , NF-kappa B/metabolismo , Síndromes do Olho Seco/terapia , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Ratos Sprague-Dawley , Ratos , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Córnea/patologia , Córnea/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismoRESUMO
PURPOSE: This study provides an updated evaluation of the prevalence and severity of acute cancer-related symptoms and quality of life (QOL) concerns among patients treated with emetogenic chemotherapy. METHODS: Patients were recruited to a larger, multi-site observational study prior to starting chemotherapy. Participants completed sociodemographic questionnaires and clinical data were abstracted via medical record review. Symptoms and QOL were assessed 5 days after starting moderately or highly emetogenic chemotherapy. Functional Assessment of Cancer Therapy - General assessed QOL concerns. Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events evaluated symptoms. Symptoms were considered severe when participants responded "severe" or "very severe." RESULTS: Participants (N = 1174) were on average 58 ± 13 years, mostly female (73%), non-Hispanic (89%), and White (87%). Most participants were diagnosed with breast (38.1%), gynecological (20%), and gastrointestinal (17.1%) cancer. The most common QOL concerns of any severity were fatigue (94%), anhedonia (89%), dissatisfaction with QOL (86%), and sleep disturbance (86%). The most common severe QOL concerns were anhedonia (44%), fatigue (40%), and inability to work (38%). Decreased appetite (74%), pain (71%), and constipation (70%) were the most common symptoms of any severity, as well as most common severe symptoms (13%, 18%, and 18%, respectively). CONCLUSION: Herein, updates are provided in regard to QOL concerns and symptoms reported by patients in the days after chemotherapy and demonstrates that concerns and symptoms have shifted in the last decade.
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Neoplasias , Qualidade de Vida , Feminino , Humanos , Masculino , Anedonia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Pessoa de Meia-Idade , IdosoRESUMO
PURPOSE: This study aimed to test the feasibility and acceptability of a digital health promotion intervention for family caregivers of patients with advanced colorectal cancer and explore the intervention's preliminary efficacy for mitigating the impact of caregiving on health and well-being. METHODS: We conducted a single-arm pilot feasibility trial of C-PRIME (Caregiver Protocol for Remotely Improving, Monitoring, and Extending Quality of Life), an 8-week digital health-promotion behavioral intervention involving monitoring and visualizing health-promoting behaviors (e.g., objective sleep and physical activity data) and health coaching (NCT05379933). A priori benchmarks were established for feasibility (≥ 50% recruitment and objective data collection; ≥ 75% session engagement, measure completion, and retention) and patient satisfaction (> 3 on a 1-5 scale). Preliminary efficacy was explored with pre- to post-intervention changes in quality of life (QOL), sleep quality, social engagement, and self-efficacy. RESULTS: Participants (N = 13) were M = 52 years old (SD = 14). Rates of recruitment (72%), session attendance (87%), assessment completion (87%), objective data collection (80%), and retention (100%) all indicated feasibility. All participants rated the intervention as acceptable (M = 4.7; SD = 0.8). Most participants showed improvement or maintenance of QOL (15% and 62%), sleep quality (23% and 62%), social engagement (23% and 69%), and general self-efficacy (23% and 62%). CONCLUSION: The C-PRIME digital health promotion intervention demonstrated feasibility and acceptability among family caregivers of patients with advanced colorectal cancer. A fully powered randomized controlled trial is needed to test C-PRIME efficacy, mechanisms, and implementation outcomes, barriers, and facilitators in a divserse sample of family caregivers. TRIAL REGISTRATION: The Caregiver Protocol for Remotely Improving, Monitoring, and Extending Quality of Life (C-PRIME) study was registered on clinicaltrials.gov, NCT05379933, in May 2022.
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Cuidadores , Neoplasias Colorretais , Humanos , Pessoa de Meia-Idade , Estudos de Viabilidade , Promoção da Saúde , Qualidade de Vida , Projetos PilotoRESUMO
PURPOSE: Little is known about late and long-term patient-reported outcomes (PROs) of immune checkpoint modulators (ICMs) outside clinical trials. We conducted a cross-sectional, mixed-methods study to describe long-term PROs among advanced melanoma patients who began standard of care treatment with ICMs at least 1 year previously. METHODS: All participants completed the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM), assessing 46 immune-related side effects on a 5-point Likert scale, and a subset completed individual interviews. Descriptive statistics were computed for quantitative data and applied thematic analysis was used to examine qualitative data. RESULTS: Participants (N = 80) had a mean age of 67 years, and the majority were male (66%), non-Hispanic White (96%), and college graduates (61%). Single-agent nivolumab was the most common first (47%) and current/recent ICM (64%). On the FACT-ICM, 98% of participants reported at least one side effect, and 78% reported moderate or severe side effects. The most common moderate or severe side effects were aching joints (43%) and fatigue (38%). In interviews (n = 20), we identified five themes regarding patients' longer-term experiences after ICMs: lasting fatigue or decline in functioning, minimal side effects, manageable thyroid and pituitary dysfunction, skin conditions can be difficult to manage, and treating the cancer is worth the side effects. CONCLUSIONS: Nearly all patients reported side effects of ICMs at least 1 year after starting treatment. Our findings suggest that ICM side effect screening and management-especially for aching joints and fatigue-are indicated during long-term care of people living with advanced melanoma.
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Inibidores de Checkpoint Imunológico , Melanoma , Medidas de Resultados Relatados pelo Paciente , Humanos , Melanoma/tratamento farmacológico , Masculino , Feminino , Idoso , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Transversais , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Adulto , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/tratamento farmacológico , Qualidade de VidaRESUMO
PURPOSE: Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18-39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study. METHODS: Participants were grouped by age (years) as follows: 18-39 (YA), 40-49, 50-64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects. RESULTS: Participants (N = 1590) were n = 81 YAs, n = 196 aged 40-49, n = 627 aged 50-64, and n = 686 aged 65 + . Average physical function was better among YAs than participants aged 50-64 (p = 0.010) and 65 + (p < 0.001), and average social function was worse among YAs than aged 65 + (p = 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40-49 OR = 0.13, 95%CI = 0.06-0.29; aged 50-64 OR = 0.10, 95%CI = 0.05-0.21; aged 65 + OR = 0.07, 95%CI = 0.04-0.15) and role dysfunction (aged 40-49 OR = 0.36, 95%CI = 0.18-0.75; aged 50-64 OR = 0.41, 95%CI = 0.22-0.78; aged 65 + OR = 0.32, 95%CI = 0.17-0.61). Participants aged 40-49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19-0.93). CONCLUSION: YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care. TRIAL REGISTRATION: NCT02328677, registered December 2014.
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Sobreviventes de Câncer , Neoplasias Colorretais , Idoso , Humanos , Adulto Jovem , Sobreviventes de Câncer/psicologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/psicologia , Emoções , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adolescente , Adulto , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: This study sought to determine the incidence and risk factors of blood transfusion among patients undergoing total knee revision (TKR) using a nationwide database. METHODS: A retrospective data analysis was conducted based on the Nationwide Inpatient Sample (NIS), enrolling patients who underwent TKR from 2010 to 2019 with complete information. The patients were divided into two groups based on whether they received blood transfusion or not. The demographic characteristics (race, sex, and age), length of stay (LOS), total charge of hospitalization, hospital characteristics (admission type, insurance type, bed size, teaching status, location, and region of hospital), hospital mortality, comorbidities, and perioperative complications were analyzed. Finally, we conducted univariate and multivariate logistic regression to identify factors that were associated with TKR patients to require blood transfusion. RESULTS: The NIS database included 115,072 patients who underwent TKR. Among them, 14,899 patients received blood transfusion, and the incidence of blood transfusion was 13.0%. There was a dramatic decrease in the incidence over the years from 2010 to 2019, dropping from 20.4 to 6.5%. TKR patients requiring transfusions had experienced longer LOS, incurred higher total medical expenses, utilized Medicare more frequently, and had increased in-hospital mortality rates (all P < 0.001). Independent predictors for blood transfusion included advanced age, female gender, iron-deficiency anemia, rheumatoid disease, chronic blood loss anemia, congestive heart failure, coagulopathy, uncomplicated diabetes, lymphoma, fluid and electrolyte disorders, metastatic carcinoma, other neurological diseases, paralysis, peripheral vascular disorders, pulmonary circulation disorders, renal failure, valvular disease, and weight loss. In addition, risk factors for transfusion in TKR surgery included sepsis, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, gastrointestinal bleeding, heart failure, renal insufficiency, pneumonia, wound infection, lower limb nerve injury, hemorrhage/seroma/hematoma, wound rupture/non healing, urinary tract infection, acute renal failure, and postoperative delirium. CONCLUSIONS: Our findings highlight the importance of recognizing the risk factors of blood transfusion in TKR to reduce the occurrence of adverse events.
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Pacientes Internados , Medicare , Humanos , Feminino , Idoso , Estados Unidos/epidemiologia , Estudos Retrospectivos , Incidência , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Extremidade InferiorRESUMO
Flat bands (FBs), presenting a strongly interacting quantum system, have drawn increasing interest recently. However, experimental growth and synthesis of FB materials have been challenging and have remained elusive for the ideal form of monolayer materials where the FB arises from destructive quantum interference as predicted in 2D lattice models. Here, we report surface growth of a self-assembled monolayer of 2D hydrogen-bond (H-bond) organic frameworks (HOFs) of 1,3,5-tris(4-hydroxyphenyl)benzene (THPB) on Au(111) substrate and the observation of FB. High-resolution scanning tunneling microscopy or spectroscopy shows mesoscale, highly ordered, and uniform THPB HOF domains, while angle-resolved photoemission spectroscopy highlights a FB over the whole Brillouin zone. Density-functional-theory calculations and analyses reveal that the observed topological FB arises from a hidden electronic breathing-kagome lattice without atomically breathing bonds. Our findings demonstrate that self-assembly of HOFs provides a viable approach for synthesis of 2D organic topological materials, paving the way to explore many-body quantum states of topological FBs.
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AIM: This study sought to identify groups of colorectal cancer patients based upon trajectories of fatigue and examine how demographic, clinical and behavioural risk factors differentiate these groups. METHOD: Patients were from six cancer centres in the United States and Germany. Fatigue was measured using the fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at five time points (baseline/enrolment and 3, 6, 12 and 24 months after diagnosis). Piecewise growth mixture models identified latent trajectories of fatigue. Logistic regression models examined differences in demographic, clinical and behavioural characteristics between fatigue trajectory groups. RESULTS: Among 1615 participants (57% men, 86% non-Hispanic White, mean age 61 ± 13 years at diagnosis), three distinct groups were identified. In the high fatigue group (36%), fatigue significantly increased in the first 6 months after diagnosis and then showed statistically and clinically significant improvement from 6 to 24 months (P values < 0.01). Throughout the study period, average fatigue met or exceeded cutoffs for clinical significance. In the moderate (34%) and low (30%) fatigue groups, fatigue levels remained below or near population norms across the study period. Patients who were diagnosed with Stage II-IV disease and/or current smokers were more likely to be in the high fatigue than in the moderate fatigue group (P values < 0.05). CONCLUSION: A large proportion of colorectal cancer patients experienced sustained fatigue after initiation of cancer treatment. Patients with high fatigue at the time of diagnosis may benefit from early supportive care.
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Neoplasias Colorretais , Qualidade de Vida , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Fadiga/etiologia , Fadiga/epidemiologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Fatores de Risco , Alemanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
The present study examined (1) intraindividual changes in the frequency of electronic nicotine delivery systems (ENDS) use across young adulthood, 18 to 30 years old, and (2) if depressive symptoms and sensation-seeking tendencies, independently and in interaction with one another, were associated with these changes. Data were from a longitudinal study of students recruited from 24 Texas colleges and followed across six waves from fall 2015 to spring 2019. Participants (n = 1298; 36.3% non-Hispanic white, 56.3% women) were 18 to 26 years old in fall 2015 and all reported past 30-day ENDS use on at least one wave. We used growth curve modeling for an accelerated longitudinal design to examine if ENDS use frequency changed with increasing age and if depressive symptoms and sensation seeking, independently and in interaction with one another, were associated with these changes. Results showed that ENDS use frequency increased with increasing age. Depressive symptoms and sensation seeking were not independently associated with more frequent ENDS use or an accelerated increase in ENDS use frequency across increasing age. However, a significant two-way interaction indicated that young adults with elevated depressive symptoms used ENDS more frequently, but only when they had higher levels of sensation seeking. Findings indicate that young adults with depressive symptoms are a heterogeneous population and that those with high levels of sensation-seeking tendencies are at elevated risk for more frequent ENDS use. Interventions for young adults high in both sensation-seeking and depressive symptoms may help prevent and decrease ENDS use.
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Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Feminino , Adulto Jovem , Adulto , Adolescente , Masculino , Estudos Longitudinais , Depressão/epidemiologia , Estudantes , SensaçãoRESUMO
Background: High prevalence of very light cigarette smoking and use of alternative tobacco products (ATPs; i.e. electronic nicotine delivery systems [ENDS], cigars, and hookah) among young adult college students are causes for concern. The purpose of this study is to examine transitions in cigarette smoking (never vs. non-current vs. very light vs. heavier) among college students across 2.5 years and determine if the use of ATPs is related to these transitions. Methods: This study used six waves of data across 2.5 years from Project M-PACT. Participants who were 18-25 years of age at baseline were included in this study (n = 4,806). Cigarette smoking state was categorized as never smoking, non-current smoking [0 cigarettes smoked per day (cpd) in past month], very light smoking (< =5 cpd in past month), and heavier smoking (>5 in past month). Multi-state Markov models were used to examine temporal transitions in the four smoking states and examine the association of time-varying current ATP use with transitions in smoking states. Results: The probabilities of remaining in a smoking state decreased over time. The time-varying current ATP use was significantly related to increased odds of transitioning from never smoking to non-current smoking, from never smoking to very light smoking, and from non-current to very light smoking. Conclusions: Findings highlight the need to prevent ATP use among college students and in turn inhibit initiation and escalation of cigarette smoking.
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Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Adulto Jovem , Humanos , Fumar Cigarros/epidemiologia , Texas/epidemiologia , Universidades , Uso de Tabaco , Fatores de Risco , Estudantes , Trifosfato de AdenosinaRESUMO
MOTIVATION: The overall association evidence of a genetic variant with multiple traits can be evaluated by cross-phenotype association analysis using summary statistics from genome-wide association studies. Further dissecting the association pathways from a variant to multiple traits is important to understand the biological causal relationships among complex traits. RESULTS: Here, we introduce a flexible and computationally efficient Iterative Mendelian Randomization and Pleiotropy (IMRP) approach to simultaneously search for horizontal pleiotropic variants and estimate causal effect. Extensive simulations and real data applications suggest that IMRP has similar or better performance than existing Mendelian Randomization methods for both causal effect estimation and pleiotropic variant detection. The developed pleiotropy test is further extended to detect colocalization for multiple variants at a locus. IMRP will greatly facilitate our understanding of causal relationships underlying complex traits, in particular, when a large number of genetic instrumental variables are used for evaluating multiple traits. AVAILABILITY AND IMPLEMENTATION: The software IMRP is available at https://github.com/XiaofengZhuCase/IMRP. The simulation codes can be downloaded at http://hal.case.edu/â¼xxz10/zhu-web/ under the link: MR Simulations software. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Causalidade , Pleiotropia Genética , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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Estudo de Associação Genômica Ampla , Hipertensão , Pressão Sanguínea/genética , Epistasia Genética , Loci Gênicos , Humanos , Hipertensão/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIMS: College students who drink are at an increased risk of driving after drinking and alcohol-involved traffic accidents and deaths. Furthermore, the persistence of driving after drinking over time underscores a need for effective interventions to prevent future drunk driving in adulthood. The present study examined whether brief alcohol interventions (BAIs) for college students reduce driving after drinking. METHODS: A two-step meta-analysis of individual participant data (IPD) was conducted using a combined sample of 6801 college students from 15 randomized controlled trials (38% male, 72% White and 58% first-year students). BAIs included individually delivered Motivational Interviewing with Personalized Feedback (MI + PF), Group Motivational Interviewing (GMI), and stand-alone Personalized Feedback (PF) interventions. Two outcome variables, driving after two+/three+ drinks and driving after four+/five+ drinks, were checked, harmonized and analyzed separately for each study and then combined for meta-analysis and meta-regression analysis. RESULTS: BAIs lowered the risk of driving after four+/five+ drinks (19% difference in the odds of driving after drinking favoring BAIs vs. control), but not the risk of driving after two+/three+ drinks (9% difference). Subsequent subgroup analysis indicated that the MI + PF intervention was comparatively better than PF or GMI. CONCLUSIONS: BAIs provide a harm reduction approach to college drinking. Hence, it is encouraging that BAIs reduce the risk of driving after heavy drinking among college students. However, there may be opportunities to enhance the intervention content and timing to be more relevant for driving after drinking and improve the outcome assessment and reporting to demonstrate its effect.
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Consumo de Álcool na Faculdade , Condução de Veículo , Dirigir sob a Influência , Adulto , Consumo de Bebidas Alcoólicas/prevenção & controle , Feminino , Humanos , Masculino , Estudantes , UniversidadesRESUMO
This paper introduces a meta-analytic mediation analysis approach for individual participant data (IPD) from multiple studies. Mediation analysis evaluates whether the effectiveness of an intervention on health outcomes occurs because of change in a key behavior targeted by the intervention. However, individual trials are often statistically underpowered to test mediation hypotheses. Existing approaches for evaluating mediation in the meta-analytic context are limited by their reliance on aggregate data; thus, findings may be confounded with study-level differences unrelated to the pathway of interest. To overcome the limitations of existing meta-analytic mediation approaches, we used a one-stage estimation approach using structural equation modeling (SEM) to combine IPD from multiple studies for mediation analysis. This approach (1) accounts for the clustering of participants within studies, (2) accommodates missing data via multiple imputation, and (3) allows valid inferences about the indirect (i.e., mediated) effects via bootstrapped confidence intervals. We used data (N = 3691 from 10 studies) from Project INTEGRATE (Mun et al. Psychology of Addictive Behaviors, 29, 34-48, 2015) to illustrate the SEM approach to meta-analytic mediation analysis by testing whether improvements in the use of protective behavioral strategies mediate the effectiveness of brief motivational interventions for alcohol-related problems among college students. To facilitate the application of the methodology, we provide annotated computer code in R and data for replication. At a substantive level, stand-alone personalized feedback interventions reduced alcohol-related problems via greater use of protective behavioral strategies; however, the net-mediated effect across strategies was small in size, on average.
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Análise de Mediação , Motivação , Intervenção em Crise , Humanos , Análise de Classes Latentes , EstudantesRESUMO
BACKGROUND: Studies of alcohol use presume valid assessment measures. To evaluate this presumption, we examined the concordance of alcohol use as measured by ecological momentary assessment (EMA) self-reports, transdermal alcohol concentration readings via the Secure Continuous Remote Alcohol Monitor (SCRAM), and retrospective self-reports via the Timeline Follow-Back (TLFB) among adults experiencing homelessness. METHODS: Forty-nine adults who reported alcohol misuse (mean age = 47, SD = 9; 57% Black; 82% men) were recruited from a homeless shelter. For 4 weeks, alcohol use was assessed: (i) 5 times or more per day by EMA, (ii) every 30 minutes by a SCRAM device worn on the ankle, and (iii) by TLFB for the past month at the end of the study period. There were 1,389 days of observations of alcohol use and alcohol use intensity for 49 participants. RESULTS: EMA and SCRAM alcohol use data agreed on 73% of days, with an interrater agreement Kappa = 0.46. A multilevel analysis of concordance of 3 measures for alcohol use yielded statistically significant correlations of 0.40 (day level) and 0.63 (person level) between EMA and SCRAM. Alcohol use was detected on 49, 38, and 33% of days by EMA, SCRAM, and TLFB, respectively. For alcohol use intensity, EMA and SCRAM resulted in statistically significant correlations of 0.46 (day level) and 0.78 (person level). The concordance of TLFB with either EMA or SCRAM was weak, especially at the day level. CONCLUSIONS: This is the first study to examine concordance of alcohol use estimates using EMA, SCRAM, and TLFB methods in adults experiencing homelessness. EMA is a valid approach to quantifying alcohol use, especially given its relatively low cost, low participant burden, and ease of use. Furthermore, any stigma associated with wearing the SCRAM or reporting alcohol use in person may be attenuated by using EMA, which may be appealing for use in studies of stigmatized and underserved populations.
Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Avaliação Momentânea Ecológica/estatística & dados numéricos , Etanol/análise , Pessoas Mal Alojadas/psicologia , Autorrelato/estatística & dados numéricos , Adulto , Feminino , Pessoas Mal Alojadas/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Pele/químicaRESUMO
BACKGROUND: To investigate the related factors influencing immune platelet transfusion refractoriness (PTR) in acute leukemia (AL) from induction to consolidation and compare management for immune PTR, so as to improve the Platelet increment in AL. METHODS: The primary analysis included 890 patients with AL, 225 of whom were the immune PTR (25 %).They are patients in our center from induction to consolidation or transplantation in the past 10 years. Flow cytometry, karyotype characteristics and other basic information were compared between the immune PTR vs control (no-PTR) groups. We analyzed the treatment outcomes of immune PTR including matched platelets, intravenous immunoglobulin (IVIG), increasing apheresis platelet does. RESULTS: Immune PTR is more likely to occur in patients with poor prognosis in acute lymphoblastic leukemia (ALL) (P = 0.01).There is a relation between NPM1 mutation and occurrence of immune PTR (P = 0.029).The incidence of PTR at 35-59Y was higher than that at <35Y(OR = 0.68, 95 % CI = 0.48-0.96) and ≥60Y(OR = 0.49,95 % CI = 0.28-0.83), and the difference was statistically significant(P = 0.03, P = 0.01).The Platelet increment with 1 unit (u) was 47.12 %, 2 u increased to 71.14 %, and the matched 2 u (75.11 %) had the best effect. IVIG improved the Platelet increment, but there was no difference between 0.4 g/kg IVIG and 1 g/kg IVIG. Immune PTR is more likely to occur in the ages of 35-60 years. CONCLUSION: There are specific AL patient characteristics which predispose to the phenomenon of immune based PTR. Meanwhile, increasing the IVIG dose could not improve Platelet increment obviously.