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PURPOSE: To investigate whether reducing the volume of intravenous iodinated contrast material injected during brain computed tomography (CT) provides reliable and accurate imaging without compromising diagnostic accuracy. METHODS: This prospective study enrolled patients undergoing enhanced brain CT at a single tertiary hospital. Subjects who agreed to participate received a reduced dose of 60 ml contrast. The images were compared to an age and gender-matched control group who received the conventional 80 cc dose. Neuroradiologists assessed image quality and interpretation using a 5-point Likert scale with six specific domains. Based on ICC, inter-rater reliability was high at 0.873. Multiple linear regression predicted overall diagnostic accuracy based on contrast dose, age, and gender. Visual Grading Characteristics (VGC) analysis was also performed to quantify regional brain enhancement differences between the two contrast groups. RESULTS: The study included 47 patients in the 60 cc group and 55 in the 80 cc control group. The results showed the 80 cc group had significantly higher enhancement ratings compared to 60 cc for all six structures assessed. The differences between groups ranged from -0.241 to -0.433 (p < 0.001) on the 5-point scale.The VGC analysis confirmed significantly greater brain parenchymal enhancement in the 80 cc group compared to the 60 cc group. CONCLUSION: The findings indicate that reducing the intravenous iodinated contrast material volume during brain CT from 80 cc to 60 cc leads to a statistically significant reduction in image quality and diagnostic accuracy. Further research with larger cohorts is needed to confirm these findings and assess the clinical impact of these differences.
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Medios de Contraste , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Medios de Contraste/administración & dosificación , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Anciano , Adulto , Inyecciones Intravenosas , Encéfalo/diagnóstico por imagen , Yodo/administración & dosificación , Intensificación de Imagen Radiográfica/métodosRESUMEN
This study aimed to investigate whether neurological patients presenting with a bias in line bisection show specific problems in bisecting a line into two equal parts or their line bisection bias rather reflects a special case of a deficit in proportional reasoning more generally. In the latter case, the bias should also be observed for segmentations into thirds or quarters. To address this question, six neglect patients with a line bisection bias were administered additional tasks involving horizontal lines (e.g., segmentation into thirds and quarters, number line estimation, etc.). Their performance was compared to five neglect patients without a line bisection bias, 10 patients with right hemispheric lesions without neglect, and 32 healthy controls. Most interestingly, results indicated that neglect patients with a line bisection bias also overestimated segments on the left of the line (e.g., one third, one quarter) when dissecting lines into parts smaller than halves. In contrast, such segmentation biases were more nuanced when the required line segmentation was framed as a number line estimation task with either fractions or whole numbers. Taken together, this suggests a generalization of line bisection bias towards a segmentation or proportional processing bias, which is congruent with attentional weighting accounts of line bisection/neglect. As such, patients with a line bisection bias do not seem to have specific problems bisecting a line, but seem to suffer from a more general deficit processing proportions.
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Lateralidad Funcional , Trastornos de la Percepción , Humanos , Trastornos de la Percepción/etiología , Atención , Sesgo , Generalización Psicológica , Percepción EspacialRESUMEN
PURPOSE: Machine learning (ML) algorithms to predict cancer survival have recently been reported for a number of sarcoma subtypes, but none have investigated undifferentiated pleomorphic sarcoma (UPS). ML is a powerful tool that has the potential to better prognosticate UPS. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of histologically confirmed undifferentiated pleomorphic sarcoma (UPS) (n = 665). Patient, tumor, and treatment characteristics were recorded, and ML models were developed to predict 1-, 3-, and 5-year survival. The best performing ML model was externally validated using an institutional cohort of UPS patients (n = 151). RESULTS: All ML models performed best at the 1-year time point and worst at the 5-year time point. On internal validation within the SEER cohort, the best models had c-statistics of 0.67-0.69 at the 5-year time point. The Multi-Layer Perceptron Neural Network (MLP) model was the best performing model and used for external validation. Similarly, the MLP model performed best at 1-year and worst at 5-year on external validation with c-statistics of 0.85 and 0.81, respectively. The MLP model was well calibrated on external validation. The MLP model has been made publicly available at https://rachar.shinyapps.io/ups_app/ . CONCLUSION: Machine learning models perform well for survival prediction in UPS, though this sarcoma subtype may be more difficult to prognosticate than other subtypes. Future studies are needed to further validate the machine learning approach for UPS prognostication.
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Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Sarcoma/terapia , Algoritmos , Neoplasias de los Tejidos Blandos/patología , Aprendizaje AutomáticoRESUMEN
Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.
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Fibroblastos Asociados al Cáncer , Neoplasias Colorrectales , Humanos , Fibroblastos Asociados al Cáncer/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Fibroblastos/patología , Tolerancia Inmunológica , Terapia de Inmunosupresión , Microambiente Tumoral , Proliferación Celular , Receptores Tipo I de Interleucina-1/genéticaRESUMEN
BACKGROUND: Contact precautions are widely used to prevent the transmission of carbapenem-resistant organisms (CROs) in hospital wards. However, evidence for their effectiveness in natural hospital environments is limited. OBJECTIVE: To determine which contact precautions, healthcare worker (HCW)-patient interactions, and patient and ward characteristics are associated with greater risk of CRO infection or colonization. DESIGN, SETTING AND PARTICIPANTS: CRO clinical and surveillance cultures from two high-acuity wards were assessed through probabilistic modelling to characterize a susceptible patient's risk of CRO infection or colonization during a ward stay. User- and time-stamped electronic health records were used to build HCW-mediated contact networks between patients. Probabilistic models were adjusted for patient (e.g. antibiotic administration) and ward (e.g. hand hygiene compliance, environmental cleaning) characteristics. The effects of risk factors were assessed by adjusted odds ratio (aOR) and 95% Bayesian credible intervals (CrI). EXPOSURES: The degree of interaction with CRO-positive patients, stratified by whether CRO-positive patients were on contact precautions. MAIN OUTCOMES AND MEASURES: The prevalence of CROs and number of new carriers (i.e. incident CRO aquisition). RESULTS: Among 2193 ward visits, 126 (5.8%) patients became colonized or infected with CROs. Susceptible patients had 4.8 daily interactions with CRO-positive individuals on contact precautions (vs 1.9 interactions with those not on contact precautions). The use of contact precautions for CRO-positive patients was associated with a reduced rate (7.4 vs 93.5 per 1000 patient-days at risk) and odds (aOR 0.03, 95% CrI 0.01-0.17) of CRO acquisition among susceptible patients, resulting in an estimated absolute risk reduction of 9.0% (95% CrI 7.6-9.2%). Also, carbapenem administration to susceptible patients was associated with increased odds of CRO acquisition (aOR 2.38, 95% CrI 1.70-3.29). CONCLUSIONS AND RELEVANCE: In this population-based cohort study, the use of contact precautions for patients colonized or infected with CROs was associated with lower risk of CRO acquisition among susceptible patients, even after adjusting for antibiotic exposure. Further studies that include organism genotyping are needed to confirm these findings.
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Infección Hospitalaria , Humanos , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Carbapenémicos/farmacología , Estudios de Cohortes , Teorema de Bayes , Control de Infecciones/métodos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Unidades de Cuidados IntensivosRESUMEN
Arithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and non-neocortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far. Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n = 73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct gray-to-gray matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit. Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.
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Mapeo Encefálico , Imagen por Resonancia Magnética , Humanos , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo , Lóbulo Parietal/diagnóstico por imagen , Corteza CerebralRESUMEN
PURPOSE: As drug-related epidemics have expanded from cities to rural areas, syringe service programs (SSPs) and other harm reduction programs have been slow to follow. The recent implementation of SSPs in rural areas demands attention to program fidelity based on core components of SSP success. METHODS: Semistructured interviews conducted with clients and staff at 5 SSPs in 5 counties within 2 Central Appalachian health districts. Interviews covered fidelity of SSP implementation to 6 core components: (1) meet needs for harm reduction supplies; (2) education and counseling for sexual, injection, and overdose risks; (3) cooperation between SSPs and local law enforcement; (4) provide other health and social services; (5) ensure low threshold access to services; and (6) promote dignity, the impact of poor fidelity on vulnerability to drug-related harms, and the risk environment's influence on program fidelity. We applied thematic methods to analyze the data. FINDINGS: Rural SSPs were mostly faithful to the 6 core components. Deviations from core components can be attributed to certain characteristics of the local rural risk environment outlined in the risk environment model, including geographic remoteness, lack of resources and underdeveloped infrastructure, and stigma against people who inject drugs (PWID) CONCLUSIONS: As drug-related epidemics continue to expand outside cities, scaling up SSPs to serve rural PWID is essential. Future research should explore whether the risk environment features identified also influence SSP fidelity in other rural areas and develop and test strategies to strengthen core components in these vulnerable areas.
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Infecciones por VIH , Abuso de Sustancias por Vía Intravenosa , Humanos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Abuso de Sustancias por Vía Intravenosa/psicología , Kentucky/epidemiología , Programas de Intercambio de Agujas , Jeringas , Región de los Apalaches/epidemiología , Infecciones por VIH/epidemiologíaRESUMEN
The Science Teaching Experience Program-Working in Science Education (STEP-WISE) provides teaching experience for postdoctoral scholars holding full-time research appointments. Through a combination of mentorship, deliberate practice, and feedback, the postdocs learn and apply inclusive, evidence-based pedagogies. STEP-WISE is integrated into postdocs' demanding schedules and is sustainable for institutions to run. Here, we assess the effectiveness of STEP-WISE. We used the Classroom Observation Protocol for Undergraduate STEM instruction to quantify instructor and student behaviors in 20 STEP-WISE class sessions from seven courses designed and taught by postdocs in the program. We found that all of the postdocs used student-centered teaching strategies. Also, using a design-based research framework, we studied the program to identify the salient components of its design. Four interconnected key elements contribute to the program's success: 1) two training sessions, 2) a precourse meeting with the mentor, 3) implementation of active-learning strategies with support, and 4) debriefing with the mentor after each class session. STEP-WISE is a replicable model to support postdocs seeking training and experience in evidence-based teaching practices geared to improving undergraduate education and transforming pedagogical practice. We conclude that high-impact teaching can be learned early in a career with streamlined training and intensive mentoring.
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Tutoría , Mentores , Humanos , Aprendizaje , Investigadores , EstudiantesRESUMEN
BACKGROUND: Guideline recommendations for the treatment of breast cancer with low hormone receptor (HR) expression (1%-9%) are ambiguous and several studies showed more similarities with HR-negative tumors than with HR strongly positive tumors (≥10%). We used a population-based 15-year cohort to compare patient characteristics and outcome of HR low positive tumors with HR-negative and HR strongly positive tumors, respectively. PATIENTS AND METHODS: A total of 38 560 women diagnosed with early invasive breast cancer between 2004 and 2018 within the scope of the Munich Cancer Registry with 4.9 million inhabitants were included. Descriptive analyses of prognostic factors, treatment, and outcome analyses using the Kaplan-Meier method; cumulative incidence in consideration of competing risks; and multivariate analyses (Cox regression and Fine-Gray model) were conducted. Endpoints were time to local recurrence (TTLR), time to lymph node recurrence (TTLNR), time to metastasis (TTM), overall survival (OS), and relative survival (RS). RESULTS: A total of 861 patients (2%) had HR low positive, 4862 (13%) HR-negative, and 32 837 (85%) HR strongly positive tumors. Within the HER2-negative cohort (n = 33 366), survival of HR low positive tumors was significantly worse than that of HR strongly positive tumors [OS hazard ratio 0.66 (95% confidence interval 0.55-0.78)], whereas between HR low positive and HR-negative tumors no significant survival difference could be detected [OS hazard ratio 0.93 (95% confidence interval 0.78-1.11)]. TTLR, TTLNR, and TTM showed similar results. By contrast, within the HER2-positive cohort (n = 5194), no statistically significant differences between the three HR groups could be detected in multivariate analyses. CONCLUSION: Current definitions for HR positivity and its clinical relevance should be reconsidered. Patients with HR low positive/HER2-negative tumors could be regarded and treated similar to patients with triple-negative tumors.
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Neoplasias de la Mama , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Femenino , Hormonas , Humanos , Recurrencia Local de Neoplasia , Pronóstico , Receptor ErbB-2 , Receptores de ProgesteronaRESUMEN
BACKGROUND: A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. PATIENTS AND METHODS: This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. RESULTS: Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). CONCLUSION: In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. CLINICAL TRIAL NUMBER: NCT02889978.
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Detección Precoz del Cáncer , Neoplasias , Biomarcadores de Tumor/genética , Metilación de ADN , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Oncogenes , Estudios ProspectivosRESUMEN
Where and when alien organisms are successfully introduced are central questions to elucidate biotic and abiotic conditions favorable to the introduction, establishment and spread of invasive species. We propose a modelling framework to analyze multiple introductions by several invasive genotypes or genetic variants, in competition with a resident population, when observations provide knowledge on the relative proportions of each variant at some dates and places. This framework is based on a mechanistic-statistical model coupling a reaction-diffusion model with a probabilistic observation model. We apply it to a spatio-temporal dataset reporting the relative proportions of five genetic variants of watermelon mosaic virus (WMV, genus Potyvirus, family Potyviridae) in infections of commercial cucurbit fields. Despite the parsimonious nature of the model, it succeeds in fitting the data well and provides an estimation of the dates and places of successful introduction of each emerging variant as well as a reconstruction of the dynamics of each variant since its introduction.
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Modelos Biológicos , Enfermedades de las Plantas/virología , Potyvirus/clasificación , Francia , Potyvirus/aislamiento & purificación , ProbabilidadRESUMEN
Opportunity exists to decrease healthcare-related exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), preserve infection control resources, and increase care capacity by reducing the time to diagnosis of coronavirus disease 2019 (COVID-19). A retrospective cohort analysis was undertaken to measure the effect of targeted rapid molecular testing for SARS-CoV-2 on these outcomes. In comparison with standard platform testing, rapid testing was associated with a 65.6% reduction (12.6 h) in the median time to removal from the isolation cohort for patients with negative diagnostic results. This translated to an increase in COVID-19 treatment capacity of 3028 bed-hours and 7500 fewer patient interactions that required the use of personal protective equipment per week.
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Prueba de Ácido Nucleico para COVID-19/estadística & datos numéricos , COVID-19/diagnóstico , COVID-19/prevención & control , Servicio de Urgencia en Hospital/estadística & datos numéricos , Control de Infecciones/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2/genética , Factores de Tiempo , Adulto JovenRESUMEN
Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE-mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra-low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra-low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti-tumour surveillance, indicating the importance of a balanced IgE-mediated immune function. Ultra-low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in-depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co-factors are warranted.
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Ácidos Nucleicos Libres de Células , Neoplasias , Humanos , Metilación , Modelos BiológicosRESUMEN
BACKGROUND: Enzalutamide and apalutamide are potent next-generation androgen receptor (AR) antagonists used in metastatic and non-metastatic prostate cancer. Metabolic, hormonal and immunologic effects of deep AR suppression are unknown. We hypothesized that enzalutamide and apalutamide suppress 11ß-hydroxysteroid dehydrogenase-2 (11ß-HSD2), which normally converts cortisol to cortisone, leading to elevated cortisol concentrations, increased ratio of active to inactive glucocorticoids and possibly suboptimal response to immunotherapy. On-treatment glucocorticoid changes might serve as an indicator of active glucocorticoid exposure and resultant adverse consequences. PATIENTS AND METHODS: Human kidney tissues were stained for AR and 11ß-HSD2 expression. Patients in three trials [neoadjuvant apalutamide plus leuprolide, enzalutamide ± PROSTVAC (recombinant poxvirus prostate-specific antigen vaccine) for metastatic castration-resistant prostate cancer (CRPC) and enzalutamide ± PROSTVAC for non-metastatic castration-sensitive prostate cancer] were analyzed for cortisol and its metabolites using liquid chromatography-mass spectrometry (LC-MS/MS). Progression-free survival was determined in the metastatic CRPC study of enzalutamide ± PROSTVAC for those with glucocorticoid changes above and below the median. RESULTS: Concurrent AR and 11ß-HSD2 expression occurs only in the kidneys of men. A statistically significant rise in cortisol concentration, cortisol/cortisone ratio and tetrahydrocortisol/tetrahydrocortisone ratio with AR antagonist treatment occurred uniformly across all three trials. In the trial of enzalutamide ± PROSTVAC for metastatic CRPC, high cortisol/cortisone ratio in the enzalutamide arm was associated with significantly improved progression-free survival. However, in the enzalutamide + PROSTVAC arm, the opposite trend was observed. CONCLUSION: Enzalutamide and apalutamide treatment toggles renal 11ß-HSD2 and significantly increases indicators of and exposure to biologically active glucocorticoids, which is associated with clinical outcomes.
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Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Cromatografía Liquida , Glucocorticoides , Humanos , Riñón , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/genética , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. PARTICIPANTS AND METHODS: The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization. RESULTS: Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I-III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for â¼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%. CONCLUSIONS: cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.
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Ácidos Nucleicos Libres de Células , Neoplasias , Biomarcadores de Tumor , Ácidos Nucleicos Libres de Células/genética , Metilación de ADN , ADN de Neoplasias/genética , Femenino , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Estudios ProspectivosRESUMEN
BACKGROUND Statewide interventions are critical to meeting the goals of the National HIV/AIDS Strategy in this country. In 2012, the North Carolina Division of Public Health developed the North Carolina State Bridge Counselor program to improve linkage to and reengagement in care for newly diagnosed persons and persons living with HIV who were out-of-care.METHODS We reviewed the planning process for the North Carolina State Bridge Counselor program, which involved a review of existing strengths-based counseling models for persons living with HIV, implementation of these models, and communication strategies with other providers. State bridge counselor responsibilities were delineated from the role of disease intervention specialists while retaining the fieldwork capability of disease intervention specialists to conduct outreach and provide services for persons living with HIV throughout the state.RESULTS Program implementation required extensive planning with stakeholders, incorporation of strengths-based counseling models, development of performance standards, and utilization of CAREWare, an HIV care software program to document referrals and data-sharing between state bridge counselors and clinics. By the end of 2014, state bridge counselor services were provided to approximately 60 of the 400 persons living with HIV (15%) who are diagnosed each quarter in North Carolina, with increasing utilization of the program.LIMITATIONS We assessed the development of this intervention specific to the North Carolina Division of Public Health, which may limit its generalizability. However, the State Bridge Counselor program was implemented in both urban and rural areas throughout the state, which increases its applicability to different public health programs throughout the country.CONCLUSION We demonstrated that a statewide State Bridge Counselor program for linkage and reengagement activities can be implemented by leveraging existing infrastructures, electronic medical records, HIV care networks, and fieldwork activities.
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Consejo , Infecciones por VIH/prevención & control , Accesibilidad a los Servicios de Salud , Aceptación de la Atención de Salud , Cooperación del Paciente , Derivación y Consulta , Infecciones por VIH/psicología , Implementación de Plan de Salud , Humanos , North CarolinaRESUMEN
We detected a long-term transient deformation signal between 2014 and 2016 in the Atacama region (Chile) using survey Global Positioning System (GPS) observations. Over an â¼150 km along-strike region, survey GPS measurements in 2014 and 2016 deviate significantly from the interseismic trend estimated using previous observations. This deviation from steady state deformation is spatially coherent and reveals a horizontal westward diverging motion of several centimeters, along with a significant uplift. It is confirmed by continuous measurements of recently installed GPS stations. We discard instrumental, hydrological, oceanic, or atmospheric loading effects and show that the transient is likely due to deep slow slip in the transition zone of the subduction interface (â¼40- to 60-km depth). In addition, daily observations recorded by a continuous GPS station operating between 2002 and 2015 highlight similar transient signals in 2005 and 2009, suggesting a recurrent pattern.
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Understanding how and when cooperative human behaviour forms in common-pool resource systems is critical to illuminating social-ecological systems and designing governance institutions that promote sustainable resource use. Before assessing the full complexity of social dynamics, it is essential to understand, concretely and mechanistically, how resource dynamics and human actions interact to create incentives and pay-offs for social behaviours. Here, we investigated how such incentives for information sharing are affected by spatial dynamics and management in a common-pool resource system. Using interviews with fishermen to inform an agent-based model, we reveal generic mechanisms through which, for a given ecological setting characterized by the spatial dynamics of the resource, the two 'human factors' of information sharing and management may heterogeneously impact various members of a group for whom theory would otherwise predict the same strategy. When users can deplete the resource, these interactions are further affected by the management approach. Finally, we discuss the implications of alternative motivations, such as equity among fishermen and consistency of the fleet's output. Our results indicate that resource spatial dynamics, form of management and level of depletion can interact to alter the sociality of people in common-pool resource systems, providing necessary insight for future study of strategic decision processes.
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High-voltage atmospheric cold plasma (HVACP) is a novel nonthermal decontamination technology that has potential for use in the food industry. In this study, HVACP was applied to treat pure aflatoxin B1 (AFB1) powder on a glass slide. AFB1 was degraded by 76% using a 5 min HVACP treatment in air having 40% relative humidity. The degradation products of AFB1 were separated, and their molecular formulas were elucidated using liquid-chromatography time-of-flight mass spectrometry (HPLC-TOF-MS). Six main degradation products were observed. The structures of the degradation products were further clarified via orbitrap mass spectrometry by means of fragmentation of the parental ions. Two degradation pathways were proposed on the basis of the structure of the degradation products. Among the six degradation products, two were ozonolysis products of AFB1. The appearance of the other four degradation products indicates that AFB1 was degraded by other reactive species besides ozone that were generated during HVACP treatment. Reactive oxygen gas species are suggested as the major agents for aflatoxin degradation during HVACP treatment. Two degradation pathways of AFB1 by HVACP treatment were proposed. One pathway involves reactions in which Hâ¢, OHâ¢, CHO⢠radicals are added. The other involves epoxidation by HO2⢠radicals and oxidation of AFB1by the combined effects of the oxidative species OHâ¢, H2O2, and O3. According to the structure-bioactivity relationship of AFB1, the bioactivity of the AFB1 samples subjected to HVACP treatment is significantly reduced because of the disappearance of the C8âC9 double bond in the furofuran ring in all of the major degradation products as well as the modification of the lactone ring, cyclopentanone, and the methoxyl group.